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1.  Use of a Novel Receptor-Targeted (CD206) Radiotracer, 99mTc-Tilmanocept, and SPECT/CT for Sentinel Lymph Node Detection in Oral Cavity Squamous Cell Carcinoma 
IMPORTANCE
Sentinel lymph node biopsy has been proposed as an alternative to up-front elective neck dissection (END) for determination of pathologic nodal status in patients undergoing surgical treatment for oral cavity squamous cell carcinoma (OSCC) with clinically negative neck (cN0). Sentinel lymph node biopsy using current standard tracer agents and imaging adjuncts such as radiolabeled sulfur-colloid and planar lymphoscintigraphy (LS), however, is associated with several drawbacks.
OBJECTIVE
To assess the preliminary utility of technetium Tc 99m(99mTc)-tilmanocept, a novel molecular imaging agent for sentinel lymph node (SLN) mapping, in OSCC.
DESIGN, SETTING, AND PARTICIPANTS
Prospective, nonrandomized, single-arm, part of an ongoing phase 3 clinical trial. Patients had previously untreated, clinically and radiographically node-negative OSCC (T1-4aN0M0) at an academic tertiary referral center.
INTERVENTIONS
Patients received a single dose of 50 μg 99mTc-tilmanocept injected peritumorally followed by dynamic planar LS and fused single-photon emission computed tomography/computed tomography (SPECT/CT) prior to surgery. Surgical intervention consisted of excision of the primary tumor and radioguided SLN dissection followed by planned END. The excised lymph nodes (SLNs and non-SLNs) underwent histopathologic evaluation for presence of metastatic disease.
MAIN OUTCOMES AND MEASURES
False-negative rate and negative predictive value of SLNB using 99mTc-tilmanocept and comparison of planar LS with SPECT/CT in SLN localization.
RESULTS
Twelve of 20 patients (60%) had metastatic neck disease on pathologic examination. All 12 had at least 1 SLN positive for metastases. No patients had a positive END node who did not have at least 1 positive SLN. These data yield a false-negative rate of 0% and negative predictive value of 100% using 99mTc-tilmanocept in this setting. Dynamic planar LS and SPECT/CT revealed a mean (range) number of hot spots per patient of 2.9 (1-7) and 3.7 (1-12), respectively. Compared with planar LS, SPECT/CT identified additional putative SLNs in 11 of 20 cases (55%).
CONCLUSIONS AND RELEVANCE
The high negative predictive value and low false-negative rate in identification of occult metastases shows 99mTc-tilmanocept to be a promising agent in SLN identification in patients with OSCC. Use of SPECT/CT improves preoperative SLN localization including delineation of SLN locations near the primary tumor when compared with planar LS imaging.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00911326
doi:10.1001/jamaoto.2013.4239
PMCID: PMC4301415  PMID: 24051744
2.  Feasibility of Sentinel Node Biopsy in Head and Neck Melanoma Using a Hybrid Radioactive and Fluorescent Tracer 
Annals of Surgical Oncology  2011;19(6):1988-1994.
Purpose
This study was designed to examine the feasibility of combining lymphoscintigraphy and intraoperative sentinel node identification in patients with head and neck melanoma by using a hybrid protein colloid that is both radioactive and fluorescent.
Methods
Eleven patients scheduled for sentinel node biopsy in the head and neck region were studied. Approximately 5 h before surgery, the hybrid nanocolloid labeled with indocyanine green (ICG) and technetium-99m (99mTc) was injected intradermally in four deposits around the scar of the primary melanoma excision. Subsequent lymphoscintigraphy and single photon emission computed tomography with computed tomography (SPECT/CT) were performed to identify the sentinel nodes preoperatively. In the operating room, patent blue dye was injected in 7 of the 11 patients. Intraoperatively, sentinel nodes were acoustically localized with a gamma ray detection probe and visualized by using patent blue dye and/or fluorescence-based tracing with a dedicated near-infrared light camera. A portable gamma camera was used before and after sentinel node excision to confirm excision of all sentinel nodes.
Results
A total of 27 sentinel nodes were preoperatively identified on the lymphoscintigraphy and SPECT/CT images. All sentinel nodes could be localized intraoperatively. In the seven patients in whom blue dye was used, 43% of the sentinel nodes stained blue, whereas all were fluorescent. The portable gamma camera identified additional sentinel nodes in two patients. Ex vivo, all radioactive lymph nodes were fluorescent and vice versa, indicating the stability of the hybrid tracer.
Conclusions
ICG–99mTc-nanocolloid allows for preoperative sentinel node visualization and concomitant intraoperative radio- and fluorescence guidance to the same sentinel nodes in head and neck melanoma patients.
Electronic supplementary material
The online version of this article (doi:10.1245/s10434-011-2180-7) contains supplementary material, which is available to authorized users.
doi:10.1245/s10434-011-2180-7
PMCID: PMC3356513  PMID: 22207047
3.  Elective neck dissection in oral carcinoma: a critical review of the evidence 
Summary
More than 50% of patients with squamous cell carcinoma of the oral cavity have lymph node metastases and histological confirmation of metastatic disease is the most important prognostic factor. Among patients with a clinically negative neck, the incidence of occult metastases varies with the site, size and thickness of the primary tumour. The high incidence rate of occult cervical metastases (> 20%) in tumours of the lower part of the oral cavity is the main argument in favour of elective treatment of the neck. The usual treatment of patients with clinically palpable metastatic lymph nodes has been radical neck dissection. This classical surgical procedure involves not only resection of level I to V lymph nodes of the neck but also the tail of the parotid, submandibular gland, sternocleidomastoid muscle, internal jugular vein and spinal accessory nerve. It is a safe oncological surgical procedure that significantly reduces the risk of regional recurrences, however it produces significant post-operative morbidity, mainly shoulder dysfunction. Aiming to reduce morbidity, Ward and Roben described a modification of the procedure sparing the spinal accessory nerve to prevent post-operative shoulder morbidity. Several clinical and pathological studies have demonstrated that the pattern of metastatic lymph node metastases occurs in a predictable fashion in patients with oral and oropharyngeal carcinoma. The use of selective supraomohyoid neck dissection as the elective treatment of the neck, in oral cancer patients, is now well established. However, its role in the treatment of clinically positive neck patients is controversial. Some Authors advocate this type of selective neck dissection in patients with limited neck disease at the upper levels of the neck, without jeopardizing neck control. The main factors supporting this approach are the usually good prognosis in patients with single levels I or II metastasis independent of the extent of neck dissection, and the low rates of level V involvement in oral cavity tumours. Furthermore, the high incidence of clinically false-positive lymph nodes in oral cavity cancer patients is well recognized. In selected cases, supraomohyoid dissection could be extended to level IV, and followed by radiotherapy when indicated. Several reports have confirmed the usefulness of minimally invasive sentinel lymph node biopsy in melanoma and breast tumours. However, only preliminary data testing the feasibility of the method exist regarding the management of oral and oropharyngeal squamous cell carcinoma. The complexity of lymphatic drainage and the presence of deep lymphatics of the neck make application of this method difficult. This attractive concept has recently been explored by several investigators who examined the feasibility of identifying the sentinel lymph node in primary echelons of drainage from oral cavity squamous carcinoma. The current knowledge of sentinel lymph node biopsy does not allow avoiding the indication of elective neck dissection in clinical practice. Sentinel lymph node biopsy cannot be considered the standard of care at this time. However, there are multi-institutional clinical trials testing this approach. Management of occult neck node metastasis continues to be a matter of debate. The role of imaging methods such as ultrasound-guided needle biopsy, sentinel node biopsy and positron emission tomography-computed tomography are still being evaluated as alternatives to elective neck dissections. Whether one of these techniques will change the current management of cervical node metastasis remains to be proved in prospective multi-institutional trials.
PMCID: PMC2640044  PMID: 17883186
Oral cancer; Treatment; Neck dissection; Lymph nodes; Elective neck dissections
4.  Sentinel lymph node biopsy in breast cancer patients after overnight migration of radiolabelled sulphur colloid 
Postgraduate Medical Journal  2004;80(947):546-550.
Objective: To evaluate the performance and feasibility of sentinel lymph node biopsy in breast cancer patients using technetium-99m (99mTc) sulphur colloid and gamma probe.
Methods: From May 2000 to March 2001, 70 patients with a tumour less than 5 cm with clinically negative axillary lymph nodes underwent sentinel node biopsy followed by standard axillary dissection. 99mTc sulphur colloid was injected around the primary tumour the day before surgery and a gamma probe was used to detect the sentinel lymph node during the surgical procedure. Sentinel lymph node biopsy was compared with standard axillary dissection for its ability to accurately reflect the final pathological status of the axillary nodes.
Results: The sentinel lymph node was successfully identified in 67 of 70 patients (95.71%). The number of sentinel lymph nodes ranged from 1–5 (mean 1.5) and non-sentinel nodes ranged from 5–22 (mean 13.3). Of the 67 patients with successfully identified sentinel lymph nodes, 43.28% (29/67) were histologically positive. Sensitivity of the sentinel lymph node to predict axilla was 82.75%; specificity was 100%. Positive and negative predictive values were 100% and 88.3% respectively. The sentinel lymph node was falsely negative in five patients, yielding an accuracy of 92.53%. Sentinel lymph node biopsy was more accurate for T1 tumours than for T2 tumours.
Conclusions: The gamma probe guided method after overnight migration of 99mTc sulphur colloid is technically feasible for detecting sentinel lymph nodes in most breast cancer patients, accurately predicting the axillary lymph node status, and appears more accurate for T1 lesions than for larger lesions. This minimally invasive axillary staging procedure represents a major advance in the surgical treatment of breast cancer.
doi:10.1136/pgmj.2003.016311
PMCID: PMC1743088  PMID: 15356357
5.  Sentinel node biopsy in early vulvar cancer 
British Journal of Cancer  2000;82(2):295-299.
Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This study evaluates the feasibility of the surgical identification of sentinel groin nodes using lymphoscintigraphy and a gamma-detecting probe in patients with early vulvar cancer. Technetium-99m-labelled colloid human albumin was administered perilesionally in 37 patients with invasive epidermoid vulvar cancer (T1–T2) and lymphoscintigraphy performed the day before surgery. An intraoperative gamma-detecting probe was used to identify sentinel nodes during surgery. A complete inguinofemoral node dissection was then performed. Sentinel nodes were submitted separately to pathologic evaluation. A total of 55 groins were dissected in 37 patients. Localization of the SN was successful in all cases. Eight cases had positive nodes: in all the sentinel node as positive; the sentinel node was the only positive node in five cases. Twenty-nine patients showed negative sentinel nodes: all of them were negative for lymph node metastases. Lymphoscintigraphy and sentinel-node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. This technique may represent a true advance in the direction of less aggressive treatments in patients with vulvar cancer. © 2000 Cancer Research Campaign
doi:10.1054/bjoc.1999.0918
PMCID: PMC2363267  PMID: 10646880
vulvar cancer; lymph node; lymphoscintigraphy; sentinel node; lymphadenectomy
6.  Role of sentinel lymph node biopsy in oral cancer 
Summary
Squamous cell carcinoma of the oral cavity represents about 2% of all malignant neoplasms and 47% of those developing in the head and neck area. The tongue is the most common site involved, and this incidence is increasing mainly in young people, possibly related to human papilloma virus infections. Prognosis depends on the stage: the 5-year survival rate of tongue squamous cell carcinoma, whatever the T stage, is 73% in pN0 cases, 40% in patients with positive nodes without extracapsular spread (pN1 ECS-), and 29% when nodes are metastatic with extracapsular spread (pN1 ECS+: p ≥ 0.0001). Nodal micrometastases (cN0 pN1) are found in up to 50% of cN0 tongue squamous cell carcinoma patients operated on the neck. At present, no clinical, imaging staging modalities or biological markers are available to diagnose nodal micrometastases. The sentinel node biopsy has been tested since 1996 in order to find a solution to this problem. The sentinel node is the first node reached by the lymphatic stream, assuming an orderly and sequential drainage from the tumour site, and should be predictive of the nodal stage. According to the literature, sentinel node biopsy is a reliable technique in selected cN0 cases, but the procedure is still experimental and should not be performed outside validation trials. Successful application of sentinel node biopsy in the head and neck region requires surgical experience and specific technical devices, including pre-operative lymphoscintigraphy and intra-operative gamma-probe. Moreover, dynamic lymphoscintigraphy seems to be able to show the lymphatic stream from the primary tumour and could allow a selective neck dissection to be tailored thus reducing the related morbidity.
PMCID: PMC2639993  PMID: 17633153
Squamous cell carcinoma; Oral cavity; Nodal metastases; Sentinel node
7.  Diagnostic value of sentinel lymph node biopsy in head and neck cancer: a meta-analysis 
This study aimed to evaluate the diagnostic reliability of sentinel lymph node biopsy in patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx by reviewing the published literature. A systematic literature review was performed using MEDLINE from 1970 to 2011. With Boolean search strings, search terms included sentinel node, supraglottic, supraglottis, tongue, head and neck, oral, pharynx, laryngeal, and larynx. Additional studies were identified through article references. Duplicate data and articles were excluded based on treating institution and study inclusion time period. Additional studies were excluded if the head and neck subsite or tumor stage was not specifically identified or if the sentinel lymph node biopsy occurred in previously treated necks. All patients had sentinel lymph node biopsy performed followed by a concurrent neck dissection. Twenty-six studies met our inclusion criteria (n = 766 patients). The pooled sensitivity and negative predictive value of SLNB for all head and neck tumors was 95 % (95 % CI 91–99 %) and 96 % (95 %CI 94–99 %), respectively. The overall sensitivity and negative predictive value of SLNB in the subset of oral cavity tumors (n = 631) was 94 % (95 % CI 89–98 %) and 96 % (95 % CI 93–99 %), respectively. One-hundred percent of oropharyngeal (n = 72), hypopharyngeal (n = 5), and laryngeal (n = 58) tumor sentinel lymph biopsy results correlated with subsequent neck dissections giving a negative predictive value of 100 %, showing that, sentinel lymph node biopsy is a valid diagnostic technique to correctly stage regional metastases in patients with head and neck squamous cell carcinoma.
doi:10.1007/s00405-012-2320-0
PMCID: PMC4167685  PMID: 23263205
Sentinel lymph node; Head and neck; Oral; pharynx; Squamous cell carcinoma
8.  Sentinel node biopsy as an indicator for pelvic nodes dissection in early stage cervical cancer. 
Journal of Korean Medical Science  2002;17(4):507-511.
The purpose of this study was to investigate the feasibility of sentinel node frozen biopsy to minimize the extensive pelvic lymph nodes dissection in early stage cervical cancer patients on the basis that the risk of skip metastasis to the paraaortic area is negligible. Twenty-six patients with early stage cervical cancer were enrolled in this study. Technetium-99m colloid albumin (Tc(99m)) was injected intradermally around the tumor for allowing preoperative lymphoscintigraphy and intraoperative hand-held gama probe detection of seninel nodes. For visual detection, isosulfan blue dye was injected into the peritumoral sites before peritoneal opening. Postoperative morbidity and negative predictive value were the endpoints of this study. The 26 patients, ranging in age from 32 to 71 yr, underwent intraoperative sentinel nodes mapping. All the patients underwent complete pelvic lymph nodes dissection including para-aortic nodes. There was one case with positive non-sentinel nodes despite the negative sentinel node by frozen biopsy (negative predictive value, 95.2%). This new technique of sentinel node mapping is safe and simple to perform. Further clinical trials using the combination of Tc(99m) and isosulfan blue dye are warranted and this technique will make a true advance for less aggressive management of patients with early stage cervical cancer.
PMCID: PMC3054900  PMID: 12172047
9.  Sentinel node detection in N0 cancer of the pharynx and larynx 
British Journal of Cancer  2002;87(7):711-715.
Neck lymph node status is the most important factor for prognosis in head and neck squamous cell carcinoma. Sentinel node detection reliably predicts the lymph node status in melanoma and breast cancer patients. This study evaluates the predictive value of sentinel node detection in 50 patients suffering from pharyngeal and laryngeal carcinomas with a N0 neck as assessed by ultrasound imaging. Following 99m-Technetium nanocolloid injection in the perimeter of the tumour intraoperative sentinel node detection was performed during lymph node dissection. Postoperatively the histological results of the sentinel nodes were compared with the excised neck dissection specimen. Identification of sentinel nodes was successful in all 50 patients with a sensitivity of 89%. In eight cases the sentinel node showed nodal disease (pN1). In 41 patients the sentinel node was tumour negative reflecting the correct neck lymph node status (pN0). We observed one false-negative result. In this case the sentinel node was free of tumour, whereas a neighbouring lymph node contained a lymph node metastasis (pN1). Although we have shown, that skipping of nodal basins can occur, this technique still reliably identifies the sentinel nodes of patients with squamous cell carcinoma of the pharynx and larynx. Future studies must show, if sentinel node detection is suitable to limit the extent of lymph node dissection in clinically N0 necks of patients suffering from pharyngeal and laryngeal squamous cell carcinoma.
British Journal of Cancer (2002) 87, 711–715. doi:10.1038/sj.bjc.6600445 www.bjcancer.com
© 2002 Cancer Research UK
doi:10.1038/sj.bjc.6600445
PMCID: PMC2364270  PMID: 12232751
sentinel node; N0 neck; squamous cell carcinoma; larynx; pharynx; occult metastases
10.  Sentinel lymph-node biopsy after previous wide local excision for melanoma 
Canadian Journal of Surgery  2001;44(6):432-434.
Objective
To document experience with sentinel lymph-node biopsy in patients who have already undergone a wide local excision for melanoma because in many centres previous wide excision has been a contraindication for sentinel lymph-node biopsy.
Design
A prospective cohort study.
Setting
A tertiary care academic cancer centre.
Patients
One hundred patients who presented with cutaneous melanoma (depth >1 mm or Clark level IV) after having undergone wide local excision of the primary lesion that was not situated in the head or neck. The follow-up was 3 years.
Interventions
Sentinel lymph-node biopsy. Patients with truncal melanoma had preoperative lymphoscintigraphy to document the nodal basins at risk. Technetium-99m sulfur colloid (0.5–1 mCi in 0.5 mL) was injected intradermally around the scar, and the sentinel lymph node was excised with the aid of a hand-held gamma detector.
Outcome measures
Accuracy of the biopsy and false-negative rates in this setting.
Results
Of the 100 patients, 44 had truncal and 56 had extremity lesions. The average tumour depth was 3.47 mm and 3.07 mm respectively. Thirty-one patients had a sentinel lymph node positive for melanoma metastasis. Biopsies were positive for melanoma in 18 (41%) truncal lesions and 13 (23%) extremity lesions. There were 3 (9%) false-negative sentinel lymph-node biopsies as diagnosed by clinically evident nodal disease subsequently appearing in the nodal basin subjected to biopsy. Two occurred in patients after large rotation flap closures of truncal lesions. The third patient had a subungual melanoma of the great toe. No disease was found in the 2 nodes dissected. Two of the 3 false-negative biopsy results were obtained before serial sections and immunohistochemical staining were used to examine the sentinel lymph nodes.
Conclusions
Sentinel lymph-node biopsies can successfully identify clinically occult nodal metastases in patients who have had previous wide local excision of a melanoma, but the false-negative rate in patients with rotation flap closures should be taken into consideration.
PMCID: PMC3692677  PMID: 11764876
11.  Sentinel lymph node biopsy is unsuitable for routine practice in younger female patients with unilateral low-risk papillary thyroid carcinoma 
BMC Cancer  2011;11:386.
Background
Sentinel lymph node (SLN) biopsy has been used to assess patients with papillary thyroid carcinoma (PTC). To achieve its full potential the rate of SLN identification must be as close to 100 percent as possible. In the present study we compared the combination of preoperative lymphoscintigraphy scanning by sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery, and methylene blue with methylene blue, alone, for sentinel node identification in younger women with unilateral low-risk PTC.
Methods
From January 2004 to January 2007, 90 female patients, ages 23 to 44 (mean = 35), with unilateral low-risk PTC (T1-2N0M0) were prospectively studied. Mean tumor size was 1.3 cm (range, 0.8-3.7 cm). All patients underwent unilateral modified neck dissection. Prior to surgery, patients had, by random assignment, identification and biopsy of SLNs by methylene blue, alone (Group 1), or by sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery and methylene blue (Group 2).
Results
In the methylene blue group, SLNs were identified in 39 of 45 patients (86.7%). Of the 39 patients, 28 (71.8%) had positive cervical lymph nodes (pN+), and 21 patients (53.8%) had pSLN+. In 7 of the 28 pN+ patients (25%), metastases were also detected in non-SLN, thus giving a false-negative rate (FNR of 38.9% (7/18), a negative predictive value (NPV) of 61.1% (11/18), and an accuracy of 82.1% (32/39). In the combined technique group, the identification rate (IR) of SLN was 100% (45/45). Of the 45 patients, 27 (60.0%) had pN+, 24 (53.3%) had pSLN+. There was a FNR of 14.3% (3/21), a NPV of 85.7% (18/21), and an accuracy of 93.3% (42/45). The combined techniques group was significantly superior to the methylene blue group in IR (p = 0.035). There were no significant differences between two groups in sensitivity, specificity, NPV, or accuracy. Location of pN+ (55 patients) in 84 patients was: level I and V, no patients; level II, 1 patient (1.2%); level III, 6 patients (7.2%); level III and IV, 8 patients (9.5%); level IV, alone, 8 patients (9.5%); level VI, 32 patients (38.1%). In all 90 patients, IR of SLN was 93.3%, FNR, 25.6%, NPV, 74.4%, and accuracy rate, 88.1 percent.
Conclusions
Compared to a single technique, there was a significantly higher SLN identification rate for the combined technique in younger female with ipsilateral, low-risk PTC (T1-2N0M0). Thus, a combined SLN biopsy technique seems to more accurately stage lymph nodes, with better identification of SLN located out of the central compartment. Regardless of the procedure used, the high FNR renders the current SLN techniques unsuitable for routine practice. Based on these results, prophylactic node dissection of level VI might be considered because 38.1% of our patients had such node metastases.
doi:10.1186/1471-2407-11-386
PMCID: PMC3224365  PMID: 21888655
12.  Sentinel lymph-node biopsy for melanoma of the trunk and extremities: the McGill experience 
Canadian Journal of Surgery  2001;44(6):428-431.
Objective
To determine the effectiveness of sentinel lymph-node (SLN) biopsy for melanoma of the trunk and extremities.
Design
Case series review.
Setting
Royal Victoria Hospital, a Canadian university hospital.
Patients
Thirty-six patients (18 women and 18 men) seen between October 1996 and December 1998 with melanoma 1 mm or more in thickness with clinically negative lymph-node basins. Follow-up was 396 days.
Interventions
SLN biopsy. Technetium-99m filtered sulfur colloid (0.5 mCi) was injected intradermally around the melanoma or the excision scar 10 to 15 minutes before the surgical skin preparation. The identification of the SLN(s) was done with a hand-held gamma probe. Local anesthesia was used mostly for inguinal SLN biopsy whereas general anesthesia was usually required for axillary SLN biopsy. Preoperative lymphoscintigraphy was used only for trunk melanomas.
Outcome measures
Morbidity, successful identification of the sentinel node and locoregional recurrence.
Results
The mean age of patients at diagnosis was 53.4 years (range from 22–76 yr). The melanomas were distributed between the lower extremities (20 patients), upper extremities (8 patients) and trunk (8 patients). The mean Breslow thickness was 2.35 mm (range from 1–8 mm). Lymphoscintigraphy accurately localized the lymph-node drainage basin for trunk melanomas. In 1 patient the SLN could not be identified because the radiocolloid failed to migrate (failure rate 2.8%). The average number of SLNs removed was 1.97. Eight patients (22%) had sentinel nodes positive for malignant disease. The postoperative complication rate was 8.5%. Seven of 8 patients with positive SLNs underwent a complete node dissection (1 patient refused). Of the completion dissections only 2 patients had positive non-SLNs. All patients with positive nodes received interferon alpha-2b as adjuvant treatment. At follow-up, 34 patients are alive with no evidence of disease, 1 patient with a positive SLN is alive with distant metastatic disease and 1 patient with a negative SLN is dead of disseminated disease.
Conclusion
SLN biopsy is a feasible technique with an acceptable failure rate and is thus a useful tool in the surgical management of melanoma.
PMCID: PMC3692676  PMID: 11764875
13.  Sentinel lymph node biopsy: technique validation at the Setúbal Medical Centre, Portugal 
ecancermedicalscience  2009;3:124.
Aims:
To evaluate the accuracy of sentinel lymph node biopsy in breast cancer patients at this institution, using combined technetium-99m (99mTc) sulphur colloid and patent blue vital dye.
Methods:
From March 2007 to July 2008, 50 patients with a tumour of less than 3 cm and with clinically negative axillary lymph nodes underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection (ALND). Sub-areolar 99mTc sulphur colloid injection was performed the day before surgery, and patent blue vital dye was also injected sub-areolarly at least 5 minutes before surgery. Sentinel lymph node was identified during the surgical procedure, using a gamma probe and direct vision. All sentinel nodes underwent frozen section analysis. Later haematoxylin and eosin staining and immunohistochemical analysis were performed. Finally, SLNB was compared with standard ALND for its ability to accurately reflect the final pathological status of the axillary nodes.
Results:
The sentinel lymph node (SLN) was identified in 48 of 50 patients (96%). The number of sentinel lymph nodes ranged from one to four (mean 1.48) and non-sentinel nodes ranged from seven to 27 (mean 14.33). Of the 48 patients with successfully identified SLNs, 29.17% (14/48) were histologically positive. Sensivity of the SLN to predict axilla was 93.75%; accuracy was 97.96%. The SLN was falsely negative in one patient—6.25% (1/16).
Conclusions:
The SLNB represents a major advance in the surgical treatment of breast cancer as a minimally invasive procedure predicting the axillary lymph node status. This validation study demonstrates the accuracy of the SLNB and its reasonable false negative rate when performed in our institute. It can now be used as the standard method of staging in patients with early breast cancer at this institution.
doi:10.3332/ecancer.2008.124
PMCID: PMC3224010  PMID: 22275996
14.  A level III sentinel lymph node in breast cancer 
Background
For accurate nodal staging, all blue and radioactive lymph nodes should be sampled during the sentinel lymph node biopsy for breast cancer. We report a case of anomalous drainage in which one of the sentinel lymph nodes was unexpectedly found in the level III axillary space.
Case presentation
A 40-year-old female underwent mastectomy for extensive high-grade ductal carcinoma in-situ (DCIS) with micro-invasion. The index lesion was located in the right upper inner quadrant. Lymphoscintigraphy was performed on the morning of surgery. Two sentinel lymph nodes were identified. At operation, 5 mls of isosulfan blue dye was injected at the same site of the radio-colloid injection. The first sentinel lymph node was found at level I and was blue and radioactive. The second sentinel node was detected in an unexpected anomalous location at level III, medial to the pectoralis minor. Both sentinel nodes were negative.
Conclusion
Sentinel node staging can lead to unexpected patterns of lymphatic drainage. For accurate staging, it is important to survey all potential sites of nodal metastasis either with preoperative lymphoscintigraphy and/or rigorous examination of regional nodal basins with the intra-operative gamma probe.
doi:10.1186/1477-7819-4-31
PMCID: PMC1557507  PMID: 16759381
15.  Sentinel lymph node biopsy for breast cancer patients using fluorescence navigation with indocyanine green 
Background
There are various methods for detecting sentinel lymph nodes in breast cancer. Sentinel lymph node biopsy (SLNB) using a vital dye is a convenient and safe, intraoperatively preparative method to assess lymph node status. However, the disadvantage of the dye method is that the success rate of sentinel lymph node detection depend on the surgeon's skills and preoperative mapping of the sentinel lymph node is not feasible. Currently, a vital dye, radioisotope, or a combination of both is used to detect sentinel nodes. Many surgeons have reported successful results using either method. In this study we have analyzed breast lymphatic drainage pathways using indocyanine green (ICG) fluorescence imaging.
Methods
We examined the lymphatic courses, or lymphatic vessels, in the breast using ICG fluorescence imaging, and applied this method to SLNB in patients who underwent their first operative treatment for breast cancer between May 2006 and April 2008. Fluorescence images were obtained using a charge coupled device camera with a cut filter used as a detector, and light emitting diodes at 760 nm as a light source. When ICG was injected into the subareola and periareola, subcutaneous lymphatic vessels from the areola to the axilla became visible by fluorescence within a few minutes. The sentinel lymph node was then dissected with the help of fluorescence imaging navigation.
Results
The detection rate of sentinel nodes was 100%. 0 to 4 states of lymphatic drainage pathways from the areola were observed. The number of sentinel nodes was 3.41 on average.
Conclusions
This method using indocyanine green (ICG) fluorescence imaging may possibly improve the detection rate of sentinel lymph nodes with high sensitivity and compensates for the deficiencies of other methods. The ICG fluorescence imaging technique enables observation of breast lymph vessels running in multiple directions and easily and accurately identification of sentinel lymph nodes. Thus, this technique can be considered useful.
doi:10.1186/1477-7819-9-157
PMCID: PMC3269998  PMID: 22132943
sentinel lymph node biopsy; breast cancer; indocyanine green; fluorescence imaging
16.  Impact of non-axillary sentinel node biopsy on staging and treatment of breast cancer patients 
British Journal of Cancer  2002;87(7):705-710.
The purpose of this study was to evaluate the occurrence of lymphatic drainage to non-axillary sentinel nodes and to determine the implications of this phenomenon. A total of 549 breast cancer patients underwent lymphoscintigraphy after intratumoural injection of 99mTc-nanocolloid. The sentinel node was intraoperatively identified with the aid of intratumoural administered patent blue dye and a gamma-ray detection probe. Histopathological examination of sentinel nodes included step-sectioning at six levels and immunohistochemical staining. A sentinel node outside level I or II of the axilla was found in 149 patients (27%): internal mammary sentinel nodes in 86 patients, other non-axillary sentinel nodes in 44 and both internal mammary and other non-axillary sentinel nodes in nineteen patients. The intra-operative identification rate was 80%. Internal mammary metastases were found in seventeen patients and metastases in other non-axillary sentinel nodes in ten patients. Staging improved in 13% of patients with non-axillary sentinel lymph nodes and their treatment strategy was changed in 17%. A small proportion of clinically node negative breast cancer patients can be staged more precisely by biopsy of sentinel nodes outside level I and II of the axilla, resulting in additional decision criteria for postoperative regional or systemic therapy.
British Journal of Cancer (2002) 87, 705–710. doi:10.1038/sj.bjc.6600359 www.bjcancer.com
© 2002 Cancer Research UK
doi:10.1038/sj.bjc.6600359
PMCID: PMC2364267  PMID: 12232750
breast cancer; lymphoscintigraphy; sentinel node; staging
17.  Sentinel Lymph Node Biopsy Accurately Stages the Regional Lymph Nodes for T1-T2 Oral Squamous Cell Carcinomas: Results of a Prospective Multi-Institutional Trial 
Journal of Clinical Oncology  2010;28(8):1395-1400.
Purpose
The validity of sentinel lymph node biopsy (SLNB) for T1 or T2, clinically N0, oral cancer was tested by correlation of sentinel node pathologic status with that of nodes within the completion neck dissection.
Methods
This prospective, cooperative group trial involved 25 institutions over a 3-year period. One hundred forty patients with invasive oral cancers, stage T1 and T2, N0 including 95 cancers of the tongue, 26 of the floor of mouth, and 19 other oral cancers were studied. The study excluded lesions with diameter smaller than 6 mm or minimal invasion. Imaging was used to exclude nonpalpable gross nodal disease. Patients underwent injection of the lesion with 99mTc-sulfur colloid, nuclear imaging, narrow-exposure SLNB, and completion selective neck dissection. The major end point was the negative-predictive value (NPV) of SLNB.
Results
In the 106 SLNBs, which were found to be pathologically and clinically node-negative by routine hematoxylin and eosin stain, 100 patients were found to have no other pathologically positive nodes, corresponding to a NPV of 94%. With additional sectioning and immunohistochemistry, NPV was improved to 96%. In the forty patients with proven cervical metastases, the true-positive rate was 90.2% and was superior for tongue tumors relative to floor of mouth. For T1 lesions, metastases were correctly identified in 100%.
Conclusion
For T1 or T2 N0 oral squamous cell carcinoma, SLNB with step sectioning and immunohistochemistry, performed by surgeons of mixed experience levels, correctly predicted a pathologically negative neck in 96% of patients (NPV, 96%).
doi:10.1200/JCO.2008.20.8777
PMCID: PMC2834497  PMID: 20142602
18.  Efficacy of high-energy collimator for sentinel node lymphoscintigraphy of early breast cancer patients 
Radiology and Oncology  2012;46(1):75-80.
Introduction
Lymphoscintigraphy is an important part of sentinel node mapping in breast cancer patients. Sometimes star shaped artefacts due to septal penetration can be problematic during imaging. In the current study, we evaluated the possibility of high energy (HE) collimators use for lymphoscintigraphy.
Patients and methods
Twenty patients with early breast carcinoma were included. Thirty minutes after radiotracer injection (99mTc-antimony sulphide colloid), anterior and lateral images were acquired using a dual head gamma camera equipped with a parallel hole low energy high resolution (LEHR) collimator on one head and HE collimator on another head. All images were reviewed by two nuclear medicine specialists regarding detectability and number of axillary sentinel nodes and presence of star artefact.
Results
All images taken by LEHR collimators showed star artefact of the injection site. No image taken by HE collimator showed this effect. In two patients the sentinel node was visible only by HE collimator. Tumour location in both of these patients was in the upper lateral quadrant and both had history of excisional biopsy. In two patients additional sentinel node was visible adjacent to the first one only on the LEHR images.
Conclusions
HE collimators can be used for sentinel lymph node mapping and lymphoscintigraphy of the breast cancer patients. This collimator can almost eliminate star-shaped artefacts due to septal penetration which can be advantageous in some cases. However, to separate two adjacent sentinel nodes from each other LEHR collimators perform better.
doi:10.2478/v10019-012-0013-3
PMCID: PMC3423765  PMID: 22933983
sentinel node; lymphoscintigraphy; collimator; HEAP; high energy all purpose; low energy high resolution; LEHR
19.  The First and Second Echelon Sentinel Lymph Node Evaluation in Oral Cancer 
The Indian Journal of Surgery  2012;75(5):377-382.
Sentinel lymph node biopsy shows promise as a minimally invasive technique that samples the first echelon (station) of nodes to predict the need for more extensive neck dissection. This paper discusses the accuracy and feasibility of sentinel node and “station II node” biopsy for predicting the status of neck in 20 patients of oral cancer. We identified sentinel node in these patients. The next higher-order nodes, that is, second echelon of nodes known as “station II nodes” were delineated by further injecting 0.1 ml of isosulfan blue dye in sentinel lymph node. Identification rate for station I nodes was 95 %. Station II nodes were identified in 84 % of patients. One patient had false negative station I node. Station II node status was false negative in two patients. “Station I and station II concept” is feasible in early-stage tumors of oral cavity.
doi:10.1007/s12262-012-0497-5
PMCID: PMC3824774  PMID: 24426480
Sentinel node (station I node); Oral cancer; Second echelon (station) node; Neck dissection
20.  SPECT/CT for Lymphatic Mapping of Sentinel Nodes in Early Squamous Cell Carcinoma of the Oral Cavity and Oropharynx 
Adequate staging and treatment of the neck in squamous cell carcinoma of the oral cavity and oropharynx (OSCC) is of paramount importance. Elective neck dissection (END) of the clinical N0-neck is widely advocated as neck treatment. With regard to the prevalence of 20–40% of occult neck metastases found in the ND specimens, the majority of patients undergo surgery of the lymphatic drainage basin without therapeutic benefit. Sentinel node biopsy (SNB) has been shown to be a safe, reliable and accurate alternative treatment modality for selected patients. Using this technique, lymphatic mapping is crucial. Previous reports suggested a benefit of single photon emission computed tomography with CT (SPECT/CT) over dynamic planar lymphoscintigraphy (LS) alone. SPECT/CT allows the surgeon for better topographical orientation and delineation of sentinel lymph nodes (SLN's) against surrounding structures. Additionally, SPECT/CT has the potential to detect more SLN's which might harbour occult disease, than LS. SPECT/CT is recommended to be used routinely, although SPECT/CT is not indispensable for successful SNB.
doi:10.1155/2011/106068
PMCID: PMC3065910  PMID: 21490726
21.  99Tc nanocolloid sentinel node procedure in papillary thyroid carcinoma: our mono-institutional experience on a large series of patients 
Summary
The sentinel lymph node was defined as the first lymph node to receive drainage from a primary cancer. The aims of this study were to investigate the efficacy of radiocolloid lymphoscintigraphy and of the hand-held gamma probe procedure for sentinel lymph node biopsy in papillary thyroid carcinoma and to evaluate these results in clinical staging. A total of 99 consecutive papillary thyroid carcinoma patients entered the study. Patients underwent radiocolloid lymphoscintigraphy before surgery. Intra-operative sentinel lymph node localization was performed using a hand-held gamma probe. Patients were observed at follow-up at 2 and 6 months and, thereafter, yearly. Sequential lymphoscintigraphy was able to identify at least one sentinel lymph node in 98/99 cases (99%), using intra-operative hand-held gamma probe, the surgeon was able to detect at least one sentinel lymph node in all cases. Sentinel lymph node metastases were diagnosed in 49%. Overall, 79 patients underwent ablative 131I therapy. The median value of thyroglobulin in N0 vs. N1 patients was 1 ng/ml vs. 1.9 ng/ml (p = 0.03) and 0.2 ng/ml vs. 1 ng/ml (p = 0.001) before and after 131I therapy, respectively. The pre-operative lymphoscintigraphy and the intra-operative gamma probe offer significant advantages over the vital dye technique, described in our previous experience. The rate of nodal involvement (49%) is very high considering that no patients had clinically palpable nodes or suspected at echography. 131I whole body scan and thyroglobulin measurements confirmed sentinel lymph node in papillary thyroid carcinoma as a reliable procedure. In patients classified N0, by sentinel lymph node biopsy, ablative 131I therapy could be avoided.
PMCID: PMC2868210  PMID: 20463837
Thyroid; Cancer; Node metastases; Sentinel lymph node; Radiocolloid lymphoscintigraphy
22.  Confirmation of Sentinel Lymph Node Identity by Analysis of Fine-Needle Biopsy Samples Using Inductively Coupled Plasma–Mass Spectrometry 
Annals of Surgical Oncology  2008;15(3):934-940.
Background
The sentinel lymph node (SLN) biopsy technique is a reliable means of determining the tumor-harboring status of regional lymph nodes in melanoma patients. When technetium 99 m-labeled antimony trisulfide colloid (99 mTc-Sb2S3) particles are used to perform preoperative lymphoscintigraphy for SLN identification, they are retained in the SLN but are absent or present in only tiny amounts in non-SLNs. The present study investigated the potential for a novel means of assessing the accuracy of surgical identification of SLNs. This involved the use of inductively coupled plasma–mass spectrometry (ICP-MS) to analyze antimony concentrations in fine-needle biopsy (FNB) samples from surgically procured lymph nodes.
Methods
A total of 47 FNB samples from surgically excised lymph nodes (32 SLNs and 15 non-SLNs) were collected. The SLNs were localized by preoperative lymphoscintigraphy that used 99 mTc-Sb2S3, blue dye, and gamma probe techniques. The concentrations of antimony were measured in the FNB samples by ICP-MS.
Results
The mean and median antimony concentrations (in parts per billion) were .898 and .451 in the SLNs, and .015 and .068 in the non-SLNs, the differences being highly statistically significant (P < .00005).
Conclusions
Our results show that ICP-MS analysis of antimony concentrations in FNB specimens from lymph nodes can accurately confirm the identity of SLNs. Used in conjunction with techniques such as proton magnetic resonance spectroscopy for the nonsurgical evaluation of SLNs, ICP-MS analysis of antimony concentrations in FNB samples could potentially serve as a minimally invasive alternative to surgery and histopathologic evaluation to objectively classify a given node as sentinel or nonsentinel and determine its tumor-harboring status.
doi:10.1245/s10434-007-9693-0
PMCID: PMC2234448  PMID: 18172734
Clinical; Fine-needle biopsy; Melanoma; Pathology; Sentinel lymph node
23.  Reoperative Selective Sentinel Lymphadenectomy Combined With Lymphoscintigraphy Is Technically Feasible for Cutaneous Tumors of the Upper Extremity After Radical Dissection of Regional Lymph Node Basins for Breast Cancer 
Eplasty  2014;14:e32.
Objective: The rising incidence of melanoma and the high prevalence of breast cancer have generated a new scientific problem—how do the regional lymph node basins function after radical lymphadenectomy and are lymphatic drainage patterns altered after radical lymphadenectomy? Furthermore, after radical lymphadenectomy, selective sentinel lymphadenectomy is still a technically feasible and valid staging tool in the upper extremity? Thus, our study asks if selective sentinel lymph node dissection is technically feasible after radical lymph node dissection of the regional draining basin of the upper extremity (axilla). Methods: Retrospective review of a prospectively maintained database of patients was reviewed to identify patients who had lymphoscintigraphy and sentinel lymph node biopsy of the upper extremity after a radical axillary node dissection procedure. Imaging and pathology results were analyzed. Results: Seven patients fulfilling the inclusion criteria were identified. The patients all had either melanoma or invasive squamous cell carcinoma, and sentinel lymph nodes were identified in 6 out of 7 patients. One patient had metastases to 2 sentinel lymph nodes. Alternative drainage pathways were identified in 29% of patients, and 14% of patients had no identifiable drainage basin on lymphoscintigraphy. Conclusions: Sentinel lymph node dissection is technically feasible after previous axillary dissection. Lymphoscintigraphy is an important perioperative tool as lymphatic drainage may be altered or not observed as evidenced in 43% of the studied patients. However, when lymphatic drainage is detected by lymphoscintigraphy, pathologically significant sentinel lymph nodes are surgically identifiable.
PMCID: PMC4166173  PMID: 25328565
lymphadenectomy; lymphoscintigraphy; melanoma; sentinel node; squamous cell carcinoma
24.  Quantitative Measurement of Melanoma Spread in Sentinel Lymph Nodes and Survival 
PLoS Medicine  2014;11(2):e1001604.
In this study, Klein and colleagues investigated the impact of minimal cancer sentinel lymph node spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival. The authors found that cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death and the best predictor of outcome was a model based on combined quantitative effects of DCCD, tumor thickness, and ulceration.
Please see later in the article for the Editors' Summary
Background
Sentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival.
Methods and Findings
We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (n = 52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3–123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61–2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ≤3 had an increased risk of dying from melanoma compared to patients with DCCD = 0 (p = 0.04; hazard ratio 1.63, 95% CI 1.02–2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories.
Conclusions
Cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and ulceration predicted outcome best, particularly at longer follow-up. If these results are validated in an independent study, establishing quantitative immunocytology in histopathological laboratories may be useful clinically.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Because the skin contains many different cell types, there are many types of skin cancer. The most dangerous type—melanoma—develops when mutations occur in melanocytes, the cells that produce the pigment melanin. Less than 5% of skin cancers are melanomas, but melanoma causes most skin cancer deaths. Early signs of melanoma are a change in the appearance of a mole (a pigmented skin blemish) or the development of a new and unusual pigmented lesion. If these signs are noticed and the melanoma is diagnosed before it has spread from the skin into nearby lymph nodes and other tissues, surgery often provides a cure. For advanced melanomas, the outlook is generally poor, although novel therapies may prolong a patient's life.
Why Was This Study Done?
When a person is diagnosed with melanoma, it is important to “stage” the tumor. Knowing the extent and severity of the melanoma helps oncologists plan treatments and estimate their patients' likely outcomes. The detection of isolated melanoma cells in sentinel lymph nodes (the nodes to which cancer cells are most likely to spread from a primary tumor) is included in melanoma staging recommendations. However, finding rare tumor cells in sentinel lymph node biopsies by examining the tissue requires the analysis of many slides from each node removed from the patient and is extremely time-consuming. In this study, the researchers investigate the predictive value of a quantitative immunocytological assay that involves disaggregation of the sentinel node and detection of disseminated cancer cells (DCCs) by immunostaining for gp100 (a marker for melanoma cells). They also use this new assay to examine the effect of increasing numbers of DCCs on melanoma-specific survival.
What Did the Researchers Do and Find?
The researchers used routine histopathology and immunocytology to analyze 1,834 sentinel lymph nodes from 1,027 patients with melanoma who underwent sentinel lymph node biopsy at one German hospital. For immunocytology, the researchers recorded the number of gp100-positive cells per million lymph node cells (the DCC density). During follow-up, 138 patients (13.4%) died from melanoma. The results indicated that increased DCC density was associated with an increased risk of death due to melanoma. Specifically, every 10-fold increase in DCC density + 1 was associated with a near doubling of the risk of death from melanoma (a hazard ratio of 1.81). Even patients with three or fewer gp100-positive cells per million lymph node cells had an increased risk of dying from melanoma compared to patients with no gp100-positive cells (hazard ratio 1.63). When other predictors of outcome such as age and primary tumor location were taken into account, DCC density was a stronger predictor of death than histopathology. Finally, a survival model that included tumor thickness, tumor ulceration, and DCC density provided survival prediction superior to that of a model based on the current standard staging recommendations.
What Do These Findings Mean?
These findings show that quantification of cancer cell dissemination from melanomas to sentinel lymph nodes is feasible and can be combined with other characteristics of the primary tumor to provide an accurate prediction of outcomes for individual patients with melanoma. Notably, the new prediction model identifies a group of patients at high risk of progression for whom the current clinical standard underestimates the risk of death. These patients may benefit from adjuvant therapies, so the new analysis presented in this study may help to stratify patients for clinical trials. Importantly, quantitative immunocytology and the new model, although internally validated in this study, need to be validated in an independent group of patients before they can be considered for routine clinical use. If external validation is successful, quantitative immunocytology, which is much less labor-intensive than histopathology, has the potential to change the routine clinical care of patients with melanoma and probably with other solid tumors, conclude the researchers.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001604.
The US National Cancer Institute provides information for patients and professionals on melanoma, cancer staging, and sentinel lymph node biopsy (in English and Spanish)
The nonprofit organization American Cancer Society provides information in several languages on cancer and how it develops and specific information on melanoma, including the AJCC system for staging and personal stories
The UK National Health Service Choices website includes an introduction to cancer and a page on melanoma that includes personal stories
The nonprofit organization Cancer Research UK provides basic information about cancer and detailed information on melanoma
doi:10.1371/journal.pmed.1001604
PMCID: PMC3928050  PMID: 24558354
25.  Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx 
BMC Cancer  2011;11:217.
Background
Prognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections.
Objectives
To determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease.
Methods
E-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance.
Results
pT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (p = 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (p = 0.005) in univariate and multivariate analysis.
Conclusion
These data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx.
Level of evidence: 2b
doi:10.1186/1471-2407-11-217
PMCID: PMC3128007  PMID: 21639893
Head and Neck squamous cell carcinoma (HNSCC); oral cavity; oropharynx; E-Cadherin (ECAD); Immunohistochemistry; Sentinel node biopsy

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