Background. Renal cell carcinoma (RCC) metastasis to the salivary glands is extremely rare. Most cases reported previously have involved the parotid gland and only six cases involving the submandibular gland exist in the current literature. Metastasis of RCC to thyroid gland is also rare but appears to be more common than to salivary glands. Methods and Results. We present the first case of simultaneous metastasis to the submandibular and thyroid glands from clear cell RCC in a 61-year-old woman who presented seven years after the primary treatment. The submandibular and thyroid glands were excised completely with preservation of the marginal mandibular and recurrent laryngeal nerves, respectively. Conclusion. Metastatic disease should always be considered in the differential diagnosis for patients who present with painless salivary or thyroid gland swelling with a previous history of RCC. If metastatic disease is confined only to these glands, prompt surgical excision can be curative.
Lymphoid tissue located in the head and neck region include multiple regional lymph node chains as well as mucosa associated lymphoid tissue of the conjunctiva, buccal and nasopharyngeal cavities (Waldeyer’s ring), and thyroid and salivary glands. This region is a rich source of antigenic stimuli including infectious agents coming from the outside environment. Many reactive conditions that affect lymphoid tissue in this region may mimic neoplasia. In fact, distinguishing between benign and malignant lymphoid proliferations in the head and neck region is a relatively frequent diagnostic challenge and in many instances, this distinction is not straightforward. It therefore behooves the practicing pathologist to be able to recognize the benign lymphoproliferative disorders that affect this region so as to effectively guide the appropriate clinical management of such patients. Kimura disease, Epstein Barr lymphadenitis, HIV associated salivary gland disease and chronic sialadenitis are benign conditions that not infrequently affect lymphoid tissue in the head and neck region and that share certain overlapping features with malignant lymphoma. In this brief review, we discuss these conditions and highlight clinicopathological features that may help distinguish them from neoplastic lymphoproliferations that may share similar features.
Kimura; HIV; EBV; Chronic sialadenitis; MALT
Nuclear DNA ploidy studies were performed by flow cytometry on extracted nuclei from 12 oncocytic tumours of the salivary gland, 65 oncocytic tumours of the kidney, and 37 oncocytic tumours of the thyroid gland from the pathology archives of the Mayo Clinic. In order to provide an interesting clinical spectrum, three different classes of well-differentiated oncocytic tumours were selected for examination. Salivary gland oncocytic tumours were chosen for their generally benign behaviour. Oncocytic thyroid cancers exhibiting malignant potential because of local invasion, were thought to represent the opposite extreme of aggressiveness. Renal oncocytic tumours were known to demonstrate an intermediate degree of malignancy. All of the oncocytic salivary gland tumours showed a 'normal' DNA histogram and had a benign clinical course. For the oncocytic tumours of the kidney, 45% of DNA histograms were normal, 40% exhibited a significant increase in the DNA tetraploid/polyploid (4C) peak, and 15% showed a DNA aneuploid peak. Three patients with a DNA tetraploid pattern developed tumour metastasis and two have died from metastatic renal cancer. Among the oncocytic thyroid cancers, 27% were normal, 22% exhibited an increased DNA tetraploid peak, and 51% had a distinct DNA aneuploid peak. None of the thyroid tumour patients with a normal DNA pattern or with an increased DNA tetraploid peak died as a result of thyroid malignancy. In contrast, 58% of patients whose thyroid tumours showed a DNA aneuploid peak subsequently died from thyroid cancer.
The lower lip is a very rare emerging site for pleomorphic adenoma. The present review is to accentuate the definition, frequency, clinical and histopathological features, differential diagnosis, prognosis, and treatment choices of pleomorphic adenoma. We reviewed the English-language literature addressing pleomorphic adenoma of the lower lip. The tumors of minor salivary glands are not frequent among whole salivary glands tumors. Pleomorphic adenoma is the most common neoplasm among the minor salivary glands. A wide excision is recommended if there is no cosmetic care and no risk of damage to the functional structures of head and neck. Malignancy of the minor salivary glands are not rare. In addition, malignant transformation of pleomorphic adenoma involved in the benign tumors of minor salivary glands are possible. Thus, awareness of the possibility of existence of a pleomorphic adenoma or a malignant tumor within a mass located on the lower lip has a mentionable importance.
Pleomorphic; adenoma; salivary glands; lip
Head and neck cancer is the fifth most common malignancy and accounts for 3% of all new cancer cases each year. Despite relatively high survival rates, the quality of life of these patients is severely compromised because of radiation-induced impairment of salivary gland function and consequential xerostomia (dry mouth syndrome). In this study, a clinically applicable method for the restoration of radiation-impaired salivary gland function using salivary gland stem cell transplantation was developed. Salivary gland cells were isolated from murine submandibular glands and cultured in vitro as salispheres, which contained cells expressing the stem cell markers Sca-1, c-Kit and Musashi-1. In vitro, the cells differentiated into salivary gland duct cells and mucin and amylase producing acinar cells. Stem cell enrichment was performed by flow cytrometric selection using c-Kit as a marker. In vitro, the cells differentiated into amylase producing acinar cells. In vivo, intra-glandular transplantation of a small number of c-Kit+ cells resulted in long-term restoration of salivary gland morphology and function. Moreover, donor-derived stem cells could be isolated from primary recipients, cultured as secondary spheres and after re-transplantation ameliorate radiation damage. Our approach is the first proof for the potential use of stem cell transplantation to functionally rescue salivary gland deficiency.
Salivary gland tumors are relatively uncommon and account for approximately 3-6% of all neoplasms of the head and neck. Tumors mostly involve the major salivary glands, 42.9-90% of which occur in the parotid glands and 8-19.5% in the sub-mandibular glands; tumors in the sub-lingual glands being uncommon. Despite the plethora of different malignant salivary gland tumor presented to pathologists for diagnosis, there is consensus on a limited number of pathologic observations that determine treatment and outcome. There are few absolutes in salivary gland tumor diagnosis given the marked spectrum and overlap of differentiated cell types that participate in the numerous benign and malignant tumors. Thus, there are enumerating antibodies that may be helpful in resolving difficult differential diagnoses when applied with astute morphologic correlation. In general, immunohistochemistry as an ancillary diagnostic tool should be used sparingly and wisely as a morphologic adjunct because of the lack of specificity of many markers for specific histologic tumor types. The aim of this review is to discuss the molecular profiling of salivary gland neoplasms and correlate this with histogenesis of salivary gland neoplasms. We have elected to discuss and illustrate some of the unusual salivary gland tumors that the practicing pathologist find difficult to diagnose. These have been selected because they readily simulate each other but have very different clinical therapies and, therefore, should be included routinely in differential diagnosis.
Histogenesis; IHC; unusual salivary gland
Malignant tumors affecting minor salivary glands present a wide range of histopathologic types. The present study sought to design a protocol for management of patients with malignancy of minor salivary glands. The data of 22 patients with malignant tumors of the minor salivary glands, surgically treated at our department in the past 10 years, were accumulated and studied. All patients underwent a diagnostic workup prior to surgery. The most useful examinations were magnetic resonance imaging of the head and neck and computerized tomography of the thorax. Wide local excision was sufficient for the majority of patients. Adjuvant treatment is indicated for high-grade, tumor-positive lymph nodes and residual disease. Malignant tumors of minor salivary glands are very rare. Therefore, design of management protocols is challenging. Management of the neck is necessary in evidence of metastasis and in high-grade and advanced-stage disease. Adjuvant treatment should be included in the treatment protocol in certain indications. Most importantly, long-term follow up is very important for all patients with malignant minor salivary tumors.
Minor salivary gland malignancy; adenoid cystic carcinoma; mucoepidermoid carcinoma
Because of the infrequence of salivary gland tumours and their complex histopathological diagnosis it is still difficult to exactly predict their clinical course by means of recurrence, malignant progression and metastasis. In order to define new proliferation associated genes, purpose of this study was to investigate the expression of human α-defensins (DEFA) 1/3 and 4 in different tumour entities of the salivary glands with respect to malignancy.
Tissue of salivary glands (n=10), pleomorphic adenomas (n=10), cystadenolymphomas (n=10), adenocarcinomas (n=10), adenoidcystic carcinomas (n=10), and mucoepidermoid carcinomas (n=10) was obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of DEFA 1/3 and 4 were analyzed by quantitative realtime PCR and compared with healthy salivary gland tissue. Additionally, the proteins encoded by DEFA 1/3 and DEFA 4 were visualized in paraffin-embedded tissue sections by immunohistochemical staining.
Human α-defensins are traceable in healthy as well as in pathological altered salivary gland tissue. In comparison with healthy tissue, the gene expression of DEFA 1/3 and 4 was significantly (p<0.05) increased in all tumours – except for a significant decrease of DEFA 4 gene expression in pleomorphic adenomas and a similar transcript level for DEFA 1/3 compared to healthy salivary glands.
A decreased gene expression of DEFA 1/3 and 4 might protect pleomorphic adenomas from malignant transformation into adenocarcinomas. A similar expression pattern of DEFA-1/3 and -4 in cystadenolymphomas and inflamed salivary glands underlines a potential importance of immunological reactions during the formation of Warthin’s tumour.
DEFA 1/3; DEFA 4; Salivary gland; Tumour; Defensins
Aims: Molecular genetic changes involved in tumorigenesis and malignant transformation of human tumours are novel targets of cancer diagnosis and treatment. This study aimed to analyse the expression of putative tumour suppressor genes, FHIT and WT-1, and tumour rejection genes, BAGE, GAGE-1/2, MAGE-1, MAGE-3, and HAGE (which are reported to be important in human cancers), in salivary gland neoplasms.
Methods: Gene expression was analysed by reverse transcription polymerase chain reaction (RT-PCR) in normal salivary gland tissue and 44 benign and malignant salivary gland tumours.
Results: Aberrant FHIT transcripts were found in one of 38 normal salivary glands, three of 28 adenomas, and two of 16 carcinomas. WT-1 mRNA was detectable in two adenomas and five carcinomas. Immunoblotting showed that WT-1 mRNA expression was associated with raised WT-1 protein concentrations. RT-PCR for detection of BAGE, GAGE, and MAGE gene expression was positive in two adenomas and nine carcinomas, but negative in normal salivary gland tissue. HAGE mRNA was found in two normal salivary glands, 11 benign, and eight malignant tumours.
Conclusions: FHIT mRNA splicing does not appear to be involved in the genesis of salivary gland neoplasms. The upregulation of WT-1 mRNA in tumours of epithelial/myoepithelial phenotype may imply a potential role of WT-1 in the genesis and/or cellular differentiation of these salivary gland tumours. The tumour rejection genes were more frequently, but not exclusively, expressed in malignant salivary gland tumours than in benign neoplasms, although none was suitable as a diagnostic marker of malignancy in salivary gland neoplasms.
salivary gland neoplasms; FHIT; WT-1; BAGE; GAGE; MAGE; HAGE
Radiation is a primary or secondary therapeutic modality for treatment of head and neck cancer. A common side effect of irradiation to the neck and neck region is xerostomia caused by salivary gland dysfunction. Approximately 40,000 new cases of xerostomia result from radiation treatment in the United States each year. The ensuing salivary gland hypofunction results in significant morbidity and diminishes the effectiveness of anti-cancer therapies as well as the quality of life for these patients. Previous studies in a rat model have shown no correlation between induction of apoptosis in the salivary gland and either the immediate or chronic decrease in salivary function following γ-radiation treatment.
A significant level of apoptosis can be detected in the salivary glands of FVB mice following γ-radiation treatment of the head and neck and this apoptosis is suppressed in transgenic mice expressing an activated mutant of Akt (myr-Akt1). Importantly, this suppression of apoptosis in myr-Akt1 mice preserves salivary function, as measured by saliva output, three and thirty days after γ-radiation treatment. In order to translate these studies into a preclinal model we found that intravenous injection of IGF1 stimulated activation of endogenous Akt in the salivary glands in vivo. A single injection of IGF1 prior to exposure to γ-radiation diminishes salivary acinar cell apoptosis and completely preserves salivary gland function three and thirty days following irradiation.
These studies suggest that apoptosis of salivary acinar cells underlies salivary gland hypofunction occurring secondary to radiation of the head and neck region. Targeted delivery of IGF1 to the salivary gland of patients receiving head and neck irradiation may be useful in reducing or eliminating xerostomia and restoring quality of life to these patients.
Metastatic malignancy to the thyroid gland is generally uncommon due to an unfavourable local thyroid micro-environment which impairs the ability of metastatic cells to settle and thrive. Metastases to the thyroid gland have however been reported to occur occasionally particularly if there has been disruption to normal thyroid tissue architecture.
We report a patient with a history of surgically resected rectal adenocarcinoma who presents with a rising serum CEA level and an 18F-FDG PET scan positive thyroid nodule which was subsequently confirmed at surgery to be a focus of metastatic rectal adenocarcinoma within a primary poorly differentiated papillary thyroid carcinoma.
Subsequent treatment involved right hemi-thyroidectomy, pulmonary wedge resection of oligometastatic metastatic colorectal cancer and chemotherapy.
Metastatic rectal carcinoma to the thyroid gland and in particular to a primary thyroid malignancy is rare and unusual. Prognosis is likely to be more dependent on underlying metastatic disease rather than the primary thyroid malignancy hence primary treatments should be tailored towards treating and controlling metastatic disease and less emphasis placed on the primary thyroid malignancy.
Diagnostic Role of Ultrasonography in Neck Swellings The study of ultrasonographic features of various neck swellings in fifty patients was done. There were 22 thyroid and thyroid related swelling, 8 salivary gland lesions, 9 lymph nodes and 14 swellings of miscellaneous origin. Various ultrasonographic features like echogenicity, echotextures were noted. There were no specific echogenicity in benign and malignant thyroid neoplasms. Various ultrasonographic features of benign and malignant salivary neoplasms and lymph nodes are described. Specific sonographic features of various miscellaneous neck swellings are also described.
Introduction. Collision tumor of the thyroid gland is defined when independent and histologically distinct tumors coexist within the gland. The presence of both papillary and squamous cell carcinoma in the thyroid gland is unusual. Suggested etiologies include embryonic remanents of squamous epithelium, chronic inflammation, or thyroid malignancies promoting squamous metaplasia. Case Presentation. An elderly patient presented with a rapid enlargement of a long-standing right thyroid nodule. The tumor was locally invasive and unresectable. Pathology revealed the diagnosis of papillary and squamous cell carcinoma of the thyroid gland. Possible primary sites for squamous cell carcinoma in upper aerodigestive tract were excluded. The patient outcome was fatal although palliative chemoradiotherapy. Discussion. Collision tumor of papillary and squamous cell carcinoma of the thyroid gland is a rare entity that may imply bad prognosis, as to the presence of the squamous portion. The best treatment includes resection of the tumor; unfortunately it is not possible in most cases.
Mucoepidermoid carcinoma is a common malignant epithelial tumor of salivary glands, but relatively rare in lung. The histological features of mucoepidermoid carcinoma of the lung are similar to its counterpart arising from the salivary glands. Here, we reported a special tumor that occurred in the medial segment of the right lower lobe in a 22-year-old man. This tumor exhibited typical features of mucoepidermoid carcinoma with 3 cell types: squamoid cells, mucin-secreting cells and cells of intermediate type. These 3 types of cells organized into cysts, nests, glands and solid patterns. Specially, the inner lining cells of some glandular structures were uniform cuboidal and hobnail-like, similar to the alveolar epithelial cells. Immunohistochemistry staining revealed that the inner lining cells of glandular structures were positive for thyroid transcription factor-1 and surfactant protein-B, used as markers of alveolar epithelial cells, and were negative for p63. These findings for the first time demonstrated a rare alveolar epithelial differentiation of glandular inner lining cells in a mucoepidermoid carcinoma of the lung.
The virtual slide(s) for this article can be found here:
Mucoepidermoid carcinoma; Lung neoplasm; Thyroid transcription factor-1; Surfactant protein-B
Salivary duct carcinoma of the parotid gland is an uncommon tumor, highly aggressive. About 200 cases have been reported in the English literature. Pathomorphologically, these tumors showed great similarities to ductal carcinoma of the female breast, which is why they described this tumor as “salivary duct carcinoma.” The authors describe a new case of salivary duct carcinoma of the parotid gland. We present the case of a 50-year-old patient with progressive facial paralysis. The MRI examination of the head showed two ill-defined formations. A malignant tumor was strongly suspected, so that a total left parotidectomy with excision of the adjacent facial nerve and left lymph node dissection was performed. Microscopic examination concluded to a salivary duct carcinoma of the left parotid gland negative with Her2/neu antibody with lymph node metastasis. There were no recurrences or metastases within 3 years of follow-up. Salivary duct carcinoma of the parotid gland is a rare tumor with an aggressive behavior. This is due to its propensity to infiltrate distant organs. The diagnosis is based on microscopic examination. Treatment modalities are non-consensual, but some authors advocate the necessity of aggressive approach, especially in tumors negative with Heur2/neu antibody. This is due to the fact that the overexpression of this antigen was reported to be associated with a poor prognosis.
Parotid gland; salivary duct carcinoma; treatment
Mucosa-associated lymphoid tissue (MALT) is a type of extra nodal malignant lymphoma seen in organs such as the stomach, thyroid and salivary glands. Furthermore, occurrence of colorectal MALT lymphoma is extremely rare. We report a case of a solitary rectal MALT lymphoma treated by surgical resection and radiotherapy. Lymphoma should be considered as a rare differential diagnosis when dealing with large bowel pathology. We would advocate the use of surgery as a primary treatment option for a medically fit patient.
The epithelial salivary gland tumours have for many years been categorised according to the 1972 World Health Organisation (WHO) classification. In 1990 a proposed revision of this classification was elaborated. In this study 101 intraoral salivary gland tumours were reclassified accordingly. In 29 of the cases the original histological diagnosis was changed, which in most cases, occurred in the benign or malignant tumour groups. In seven cases the diagnosis was changed from benign to malignant or vice versa. The results of this study show that the histological classification of intraoral salivary gland tumours remains difficult, even when applying the new WHO classification.
Local control in malignant salivary gland tumours is dose dependent. High local control rates in adenoid cystic carcinomas could be achieved by highly conformal radiotherapy techniques and particle (neutron/carbon ion) therapy. Considering high doses are needed to achieve local control, all malignant salivary gland tumours probably profit from the use of particle therapy, which in case of carbon ion treatment, has been shown to be accompanied by only mild side-effects.
The COSMIC trial is a prospective, mono-centric, phase II trial evaluating toxicity (primary endpoint: mucositis ≥ CTCAE°3) and efficacy (secondary endpoint: local control, disease-free survival) in the combined treatment with IMRT and carbon ion boost in 54 patients with histologically proved (≥R1-resected, inoperable or Pn+) salivary gland malignancies. Patients receive 24 GyE carbon ions (8 fractions) and IMRT (50 Gy at 2.0 Gy/fraction).
The primary objective of COSMIC is to evaluate toxicity and feasibility of the proposed treatment in all salivary gland malignancies.
Clinical trial identifier NCT 01154270
Myoepithelioma is a rare neoplasm of the salivary glands, generally occurring in the parotid gland and less often in the minor accessory salivary gland of the oral cavity. The histological appearance includes solid, myxoid and reticular growth patterns. Vimentin and S-100 protein are very sensitive but non-specific immunohistochemical markers of neoplastic myoepithelium. Conservative surgery is the treatment of choice. A case of myoepithelioma of the minor salivary gland of the cheek with low grade malignancy is described, focusing on clinical behaviour, histopathological and immunohistochemical features and differential diagnosis.
Salivary gland tumour; Minor salivary gland; Myoepithelioma; Diagnosis
Confusion still prevails regarding the selection of patients with thyroid nodules for surgical treatment. Classical features of malignancy do not apply to growths of the thyroid gland. Duration, size, presence of calcification, scintiscanning and response to thyroid feeding are not, in themselves, reliable indicators of the absence or presence of malignancy. In 78 personal thyroidectomies there was a 60% overall neoplasm rate and a 25% malignancy rate. Operation is indicated for the thyroid lesion which is solitary, cold, unresponsive to thyroid feeding or accompanied by obvious evidence of malignancy. Recent experience indicates that thyroid surgery has a low morbidity and negligible mortality. Surgical treatment of the common forms of thyroid cancer yields excellent results if it is complete and is expertly done.
Micro–single-photon emission computed tomography (SPECT) provides a noninvasive way to evaluate the effects of genetic and/or pharmacological modulation on sodium-iodide symporter (NIS)–mediated radionuclide accumulation in mouse thyroid and salivary glands. However, parameters affecting image acquisition and analysis of mouse thyroids and salivary glands have not been thoroughly investigated. In this study, we investigated the effects of region-of-interest (ROI) selection, collimation, scan time, and imaging orbit on image acquisition and quantification of thyroidal and salivary radionuclide accumulation in mice.
The effects of data window minima and maxima on thyroidal and salivary ROI selection using a visual boundary method were examined in SPECT images acquired from mice injected with 123I NaI. The effects of collimation, scan time, and imaging orbit on counting linearity and signal intensity were investigated using phantoms filled with various activities of 123I NaI or Tc-99m pertechnetate. Spatial resolution of target organs in whole-animal images was compared between circular orbit with parallel-hole collimation and spiral orbit with five-pinhole collimation. Lastly, the inter-experimental variability of the same mouse scanned multiple times was compared with the intra-experimental variability among different mice scanned at the same time.
Thyroid ROI was separated from salivary glands by empirically increasing the data window maxima. Counting linearity within the range of 0.5–14.2 μCi was validated by phantom imaging using single- or multiple-pinhole collimators with circular or spiral imaging orbit. Scanning time could be shortened to 15 minutes per mouse without compromising counting linearity despite proportionally decreased signal intensity. Whole-animal imaging using a spiral orbit with five-pinhole collimators achieved a high spatial resolution and counting linearity. Finally, the extent of inter-experimental variability of NIS-mediated radionuclide accumulation in the thyroid and salivary glands by SPECT imaging in the same mouse was less than the magnitude of variability among the littermates.
The impacts of multiple variables and experimental designs on micro-SPECT imaging and quantification of radionuclide accumulation in mouse thyroid and salivary glands can be minimized. This platform will serve as an invaluable tool to screen for pharmacologic reagents that differentially modulate thyroidal and salivary radioiodine accumulation in preclinical mouse models.
A new series of inoculations into cats of the filtered sterile salivary secretions derived from cases of parotitis has been described. They confirm the observations made in 1915–1916 and extend them to include the epidemic parotitis occurring in our military forces. Incidentally confirmatory evidence of the filterable nature of the causative agent of mumps has been obtained. It has been determined that the saliva of man and of inoculated cats, and the inoculated glands of the latter animals, contain the filterable, infective agent. The lesions present in the inoculated organs conform to those described in our first publication. In addition, the lymph glands adjacent to the salivary glands on the uninoculated side were sometimes found to be swollen and to exhibit microscopic lesions. Probably the involvement resulted from salivary and lymphatic infection. The "virus" of parotitis was detected most readily in the saliva during the first 3 days of the disease, less easily on the 6th day, and not at all on the 9th day. It was detected also in the blood of patients showing marked constitutional symptoms, and in the saliva of a case of recurrent mumps at the periods of enlargement of the parotid glands, but not 2 weeks after the swelling had subsided. It was not detected in the cerebrospinal fluid.
Malignant salivary gland tumors are rare. They represent less than one percent of all head and neck tumors. Approximately three fourths of all salivary gland tumors occur in the major salivary glands.
Traditionally, the treatment of choice for these tumors is surgery. The majority of these tumors reoccur after curative surgical procedures. Local recurrence rate following surgery varies with the histology, grade, and extent of the disease.
In spite of high local recurrence rate following curative surgical treatment of these tumors, radiotherapy has seldom been used as an adjuvant to surgery. The value of elective postoperative radiation therapy for subclinical microscopic disease was not recognized. Review of the literature supports the improved local control rate with the use of immediate postoperative radiotherapy. Radiation therapy proved to be effective as an adjuvant to surgery. A local control rate of better than 40 percent can be achieved by radiation therapy as a sole modality in inoperable and locally advanced cases. Radiation therapy provides an excellent palliation for locally advanced tumors or symptomatic metastases.
Among salivary gland neoplasms, metastasizing pleomorphic adenoma (MPA) constitutes an extremely rare group of tumors. The present paper reports a case of pleomorphic adenoma (PA) in submandibular gland that, after more than 30 years of initial treatment, recurred and metastasized to ipsilateral neck lymph nodes and parotid gland. In an attempt to elucidate the malignant behavior of metastasizing pleomorphic adenoma, we performed Ki-67, p53, p16, and bcl-2 immunohistochemistry staining of our case sample. Many immunohistochemistry staining studies have been done on malignant salivary gland tumors. However, to the best of our knowledge no immunohistochemistry staining of the aforementioned markers has been previously performed on metastasizing pleomorphic adenoma.
Salivary adenoid cystic carcinoma (SACC) is one of the most common malignancies of salivary gland. Recurrence or/and early metastasis is its biological properties. In SACC, neoplastic myoepithelial cells secrete proteoglycans unconventionally full of the cribriform or tubular and glandular structures of SACC. Literatures have demonstrated that extracellular matrix provided an essential microenvironment for the biological behavior of SACC. However, there is rare study of the effect of proteoglycans on the potential metastasis of SACC.
In this study, human xylosyltransferase-I (XTLY-I) gene, which catalyzes the rate-limited step of proteoglycans biosynthesis, was knocked down by RNA interference (RNAi) to inhibit the proteoglycans biosynthesis in SACC cell line with high tendency of lung metastasis (SACC-M). The impact of down-regulated proteoglycans on the metastasis characters of SACC-M cells was analyzed and discussed. This research could provide a new idea for the clinical treatment of SACC.
The eukaryotic expression vector of short hairpin RNA (shRNA) targeting XTLY-I gene was constructed and transfected into SACC-M cells. A stably transfectant cell line named SACC-M-WJ4 was isolated. The XTLY-I expression was measured by real-time PCR and Western blot; the reduction of proteoglycans was measured. The invasion and metastasis of SACC-M-WJ4 cells were detected; the effect of down-regulated proteoglycans on the potential lung metastasis of nude mice was observed, respectively.
The shRNA plasmid targeting XTLY-I gene showed powerful efficiency of RNAi. The mRNA level of target gene decreased by 86.81%, the protein level was decreased by 80.10%, respectively. The silence of XTLY-I gene resulted in the reduction of proteoglycans significantly in SACC-M-WJ4 cells. The inhibitory rate of proteoglycans was 58.17% (24 h), 66.06% (48 h), 57.91% (72 h), 59.36% (96 h), and 55.65% (120 h), respectively. The reduction of proteoglycans suppressed the adhesion, invasion and metastasis properties of SACC-M cells, and decreased the lung metastasis of SACC-M cells markedly either.
The data suggested that the silence of XTLY-I gene in SACC-M cells could suppress proteoglycans biosynthesis and secretion significantly. The reduction of proteoglycans inhibited cell adhesion, invasion and metastasis of SACC-M cells. There is a close relationship between proteoglycans and the biological behavior of SACC.