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author:("Ko, Young-heh")
1.  Prediction of Lymph Node Metastasis by Tumor Dimension Versus Tumor Biological Properties in Head and Neck Squamous Cell Carcinomas 
Purpose
Lymph node metastasis (LNM) is a strong prognostic factor in many solid cancers, including head and neck squamous cell carcinomas (HNSCC), and LNM can be dependent upon primary tumor biology, as well as tumor dimension. Here, we investigate the relative risk of LNM in accordance to tumor dimension and biology in HNSCC subsites.
Materials and Methods
Medical data of 295 HNSCC patients who had undergone the initial curative surgery (oral tongue 174, oropharynx 75, hypopharynx 46) were analyzed to identify the significant predictive factor for LNM. Tumor volume and thickness were set as tumor dimensional variables, and biological variables included lymphovascular, perineural invasion, and tumor differentiation. Statistical analyses were conducted to assess the predictability of LNM from variables, and subgroup analyses according to the tumor subsites. In addition, we evaluated the impacts of tumor dimension and biological variables on the treatment outcomes and survival in HNSCC subsites.
Results
The overall tumor dimension and biological variables had a similar impact on the prediction of LNM in HNSCC (area under the curve, 0.7682 and 0.7717). The prediction sensitivity of LNM in oral tongue cancer was mainly dependent on tumor dimension, while LNM in oroand hypo-pharynx cancers was more influenced by biological factors. Survival analyses also confirmed that biological factor was more powerful in estimating disease-free survival of hypopharyngeal cancer patients, while tumor dimension was more significant in that of oral cancer patients.
Conclusion
Tumor dimension and biology have a significant, tumor subsite-dependent impact on the occurrence of LNM and disease-free survival in HNSCC.
doi:10.4143/crt.2014.332
PMCID: PMC4720059  PMID: 25761475
Lymphatic metastasis; Head and neck neoplasms; Tumor burden; Tumor biological markers; Neoplasm metastasis
2.  High-throughput profiling identifies clinically actionable mutations in salivary duct carcinoma 
Background
Salivary duct carcinoma (SDC) is a highly aggressive subtype of salivary gland cancers and there is no established standard therapy for this disease. Thus, development of molecular markers for SDC will be important to guide the diagnosis and therapy of this aggressive tumor.
Methods
We performed next-generation sequencing using the Ion Torrent AmpliSeq cancer panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes, and we analyzed copy number variations (CNVs) of 21 genes by NanoString nCounter for 37 patients with SDC. Fluorescent in situ hybridization was also conducted to confirm ERBB2 gene amplification. Clinical records and tumor histopathology of the patients were retrospectively reviewed.
Results
Genetic alterations were detected in 29 of 37 (78.3%) tumors, including mutations in PIK3CA (N = 9, 24.3%), ERBB2 (N = 4, 10.8%), and EGFR (N = 4, 10.8%). To our knowledge, this is the first time that ERBB2 mutations have been reported in this tumor type. Both PIK3CA and ERBB2 mutation status were associated with poor overall survival, but without statistical significance. ERBB2 amplification was strong and common in SDC and almost all cases also exhibited EGFR and ERBB3 amplifications.
Conclusions
This study reports the largest and most comprehensive analysis of DNA aberrations in SDC. Our results show that PIK3CA and/or ERBB2 alterations in the development of SDC might be a useful diagnostic tool and could serve as a potential therapeutic target.
doi:10.1186/s12967-014-0299-6
PMCID: PMC4216375  PMID: 25343854
Salivary duct carcinoma; Next-generation sequencing; Molecular markers; PIK3CA; ERBB2; EGFR
3.  Spontaneous regression of metastatic cancer cells in the lymph node: a case report 
BMC Research Notes  2014;7:293.
Background
Spontaneous regression of a malignant tumor is the phenomenon of disappearance of cancer cells without any treatments and it can be induced by an enhanced tumor-targeting immune response. However, there has not been a comprehensive immunological overview to compare the tumor-regressed lymph nodes and metastatic lymph nodes in the same patient.
Case presentation
We conducted a histologic analysis of various immune cells in an Asian female patient with buccal cancer (squamous cell carcinomas), in which the spontaneous regression of metastatic lymphadenopathy was confirmed by surgical pathology. The immune cell profiles between the metastatic nodes and the tumor-regressed nodes were compared. Tumor regression was confirmed by hematoxylin & eosin and cytokeratin/Ki-67 staining. Distinct differences were observed in Foxp3(+) regulatory T (Treg) cells and CD56(+) natural killer (NK) cells; a higher density of Foxp3(+) Treg cells was found in metastatic lymph nodes and more infiltration of CD56(+) NK cells in tumor regressed lymph nodes. Other immune cell populations (CD4, CD8, CD20, CD68, CD86, CD123, CD11c, and mannose receptor) showed no discernible differences in marker expression in the nodes examined.
Conclusion
Less recruitment of Treg and high infiltration of NK cells were key features in tumor-regressed lymph nodes. Modulation of Treg or NK cells may be a good therapeutic method to control lymph node metastasis.
doi:10.1186/1756-0500-7-293
PMCID: PMC4025537  PMID: 24885770
Neoplasms; Lymph nodes; Lymphatic metastasis; Spontaneous neoplasm regression; Cellular immunity
4.  The Clinical Usefulness of 18F-FDG PET/CT for the Evaluation of Lymph Node Metastasis in Periorbital Malignancies 
Korean Journal of Radiology  2009;10(1):1-7.
Objective
The aim of this study was to assess the clinical role of 18F-FDG PET/CT for the evaluation of lymph node metastasis in periorbital malignancies, compared with CT alone.
Materials and Methods
We analyzed eighteen PET/CT and CT scans in 15 patients with biopsy-proven periorbital malignancies. We compared the diagnostic capabilities of PET/CT and CT with regard to nodal metastasis by level-by-level analysis and by N staging prediction. The reference standards were surgical pathology (n = 7) from dissected lymph node specimens and the results from radiological follow-up (n = 11, mean 20.5 months; range 10-52 months). Moreover, any changes in patient care as prompted by PET/CT were recorded and compared with treatment planning for CT alone.
Results
PET/CT had a sensitivity of 100%, while CT had a sensitivity of 57% (p = 0.03) for nodal metastasis by level-by-level analysis. PET/CT had a specificity of 97%, positive predictive value of 93%, negative predictive value of 100%, and diagnostic accuracy of 98%, while the CT values for these same parameters were 97%, 89%, 82%, and 84%, respectively. PET/CT correctly predicted N staging with an accuracy of 100%, while CT was only 83% accurate (p = 0.01). Regarding the impact on patient care, the extent of surgery for regional lymph nodes and the treatment decision were modified by PET/CT in 39% of patients.
Conclusion
PET/CT could provide useful information in the management of regional lymph node metastases in patients with periorbital malignancies.
doi:10.3348/kjr.2009.10.1.1
PMCID: PMC2647179  PMID: 19182496
18F-FDG; PET/CT; Computed tomography (CT) scans; Lymphatic Metastasis; Eyelid Neoplasm
5.  Sentinel Lymph Node Radiolocalization with 99mTc Filtered Tin Colloid in Clinically Node-Negative Squamous Cell Carcinomas of the Oral Cavity 
Journal of Korean Medical Science  2006;21(5):865-870.
The objective of this study was to evaluate the feasibility of sentinel lymph node biopsy by using a radiotracer lymphatic mapping technique in patients with squamous cell carcinoma of the oral cavity, and the diagnostic value of this technique. We studied twenty patients with previously untreated squamous cell carcinomas of the oral cavity and N0 necks. After the peritumoral injection of 99mTc filtered tin colloid preop-eratively, lymphoscintigraphy and intraoperative mapping using a gamma detector were performed to localize sentinel nodes. An open biopsy of the sentinel node was followed by complete neck dissection. We identified the sentinel nodes in 19 of 20 patients (95.0%) by lymphoscintigraphy and in all (100%) by intraoperative gamma detector. In all cases, the status of the sentinel node accurately predicted the pathologic status of the neck with the false negative rate being 0%. The negative predictive value for the absence of cervical metastases was 100%. In conclusion, our radio-localization technique of sentinel nodes using 99mTc filtered tin colloid in N0 squamous cell carcinomas of the oral cavity is technically feasible and appears to accurately predict the presence of the occult metastatic disease.
doi:10.3346/jkms.2006.21.5.865
PMCID: PMC2721997  PMID: 17043421
Sentinel Lymph Node Biopsy; Lymphatic Metastasis; Mouth Neoplasms; Radionuclide Imaging

Results 1-5 (5)