Salivary Gland Adenocarcinoma Research Articles

Searching for mammary analog secretory carcinoma of salivary gland among its mimics

Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly. Positivity for mammaglobin and S-100, and negativity for ANO1 are useful screening tools before confirmatory molecular studies.

Transglutaminase 2 mRNA Expression in Salivary Gland Tumor Cell Line

Purpose: Transglutaminase 2 (TGase 2) is expressed by tumor necrosis factor-<TEX>${\alpha}$</TEX> in various carcinoma. The role of TGase 2 expression in salivary gland tumors is not clear yet. Established slaivary gland tumor (SGT)cell line has been used to study the pathogenesis of salivary gland adenocarcinoma on a cellular level in vitro. The pupose of this study were to examine mRNA expression of TGase 2 in SGT cell line compared to other tumor cell lines, and to apply these results to the pathogenesis of salivary gland tumor. Materials and Methods: After SGT, SCC-15, HN 4, and HeLa tumor cell lines were cultured under preconfl uency, and 3 days after postconfl uency, the cells were harvested for total RNA extraction and cDNA preparation. Result: Reverse transcription polymerase chain reaction for semiquantitative mRNA analysis was done. TGase 2 mRNA expression was not induced by confl uency in all the cell lines. TGase 2 mRNA expression was variable but markedly enhanced in SGT cell line. Conclusion: mRNA expression of TGase 2 should play an important role in the pathogenesis of SGT cell line originated from ductal cell.

Basal Cell Adenocarcinoma of the Minor Salivary Glands Involving Palate and Maxillary Sinus

Basal cell adenocarcinoma (BCAC) is a rare neoplasm accounting for only 2.9% of all salivary gland neoplasms. BCAC involving palatal minor salivary glands are exceedingly rare, and only 10 cases have been reported in the literature. The treatment of choice is surgical excision. Here, we report a case of a 55-year-old male patient with massive BCAC of palatal minor salivary gland extending into the maxillary sinus. This is the first case of BCAC treated by radiotherapy followed by chemotherapy. A follow-up check conducted after 14-months showed good prognosis.

Salivary Gland Adenocarcinoma in a Domestic Rabbit (Oryctolagus cuniculus)

A 2.4kg, 7-year-old, female Rex rabbit was presented with a 4-month history of a left-sided head tilt, difficulty in mastication, lethargy, and chronic wasting. Diagnostic testing of the patient revealed a severe heterophilic leukocytosis and radiographic images of the skull radiographs indicated irregularity of the left tympanic bulla. A computed tomographic scan highlighted a heterogeneously contrast-enhancing mass, ventral and rostral to the left tympanic bulla, with contrast enhancement of the meninges on the left, consistent with an aggressive neoplasm. The patient was euthanized and the mass was identified as a salivary gland adenocarcinoma. The gland of origin is suspected to be the left parotid, owing to its location and close association with normal parotid tissue. To the authors' knowledge, this is the first report of a salivary gland adenocarcinoma in a domestic rabbit. A computed tomography (CT) scan and histopathology examination were useful modalities for identifying the neoplasm in this case.

Human papillomavirus–associated adenocarcinoma of the base of the tongue

Human papillomavirus (HPV) is a major cause of oropharyngeal squamous cell carcinoma with characteristic clinical and pathologic features relative to their non-HPV-associated counterparts. Here we describe 2 cases of HPV-associated adenocarcinoma of the oropharynx. Both cases arose at the base of the tongue, and neither had the histologic or immunohistochemical features of a primary salivary gland tumor or metastasis from another location. One patient had metastases to neck lymph nodes and the lungs and died of disease 37 months after diagnosis. Evidence for an HPV association consisted of strong diffuse expression of p16, polymerase chain reaction-based detection of HPV16 DNA sequences, and localization of HPV by in situ hybridization within tumor cells of both primary and metastatic lesions. These results further expand the spectrum of HPV-associated head and neck malignancy. This rare entity should be distinguished from primary salivary gland adenocarcinoma and may be a candidate for HPV-specific targeted therapies.

Primary intestinal‐like adenocarcinoma of major salivary glands: 2 instances of previously undocumented phenotype

Primary intestinal-like adenocarcinoma of the major salivary glands has not previously been reported. The clinical and radiological findings of 2 patients with primary submandibular and sublingual tumors are presented. Histopathologic and immunohistochemical examinations of tumor sections were performed. Metastatic workup for distant occult primary was carried out. The light-optic and the immunomarkers revealed intestinal-like adenocarcinoma consistent with upper respiratory tract origin. Metastatic workup of both patients was negative for primary gastro-intestinal primary. Primary intestinal-like adenocarcinoma can develop in major salivary glands and should be considered in the differential diagnosis.

Cribriform adenocarcinoma of minor salivary glands may express galectin-3, cytokeratin 19, and HBME-1 and contains polymorphisms of RET and H-RAS proto-oncogenes

The aim of the study was to further elucidate the immunohistochemical and genetic characteristics of cribriform adenocarcinoma of minor salivary glands (CAMSG). The study comprised five CAMSG from two males and three females, aged 21-72 years. Four tumors were localized at the base of tongue and one in the floor of mouth. At the time of diagnosis, four tumors had metastasised to regional lymph nodes. After tumor resection, two patients were treated by radiotherapy and one by chemoradiotherapy. During the follow-up (median 14 months), two patients developed lymph node metastasis. Microscopically, all tumors showed cribriform, papillary, follicular, and microcystic growth patterns. The tumor cells displayed vesicular nuclei with intranuclear grooves. Immunohistochemically, all tumors showed expression of cytokeratin (CK) 7, CK8, CK18, vimentin, smooth muscle actin, calponin, S-100 protein, and p16 protein. In addition, we observed expression of galectin-3, CK19, and HBME-1, but not of thyroglobulin and TTF-1. No mutations of RET, BRAF, K-RAS, H-RAS, and N-RAS proto-oncogenes were detected. However, in RET proto-oncogene, we found polymorphisms Gly691Ser (exon 11) and Ser904Ser (exon 15) in one case, p.Leu769Leu (exon 13) in one case, and variant p.IVS14-24 G/A of intron 14 in two cases, and in H-RAS proto-oncogene we found polymorphism 81 T-C (exon 1) in three cases. Thyroglobulin and TTF-1 are the only useful markers in the differential diagnosis between CAMSG and papillary thyroid carcinoma as both tumors may express galectin-3, CK19, and HBME-1. The RET, H-RAS, and N-RAS proto-oncoogenes are not mutated in CAMSG.

Adenocarcinoma of the sublingual salivary gland – A case report

BackgroundThis report and review of literature aimed to assess a case of adenocarcinoma of sublingual salivary gland. MethodWe present a case of a 52-year-old female with adenocarcinoma of sublingual salivary gland displaying painful swelling in the floor of the mouth, which was affecting her speech and mastication. ConclusionSurgery is the treatment of choice for malignant sublingual gland tumors, but the type of surgical intervention depends on the extent of the primary tumor itself. Even though the tumors of the sublingual salivary gland are rare, they are a diagnostic challenge to every head and neck surgeon.

Adenocarcinoma of the parotid salivary gland in a cow

A 6-year-old Girolando dairy cow was presented for evaluation of a large subcutaneous facial mass. Fine-needle aspirates of the mass contained many neoplastic cells with high nuclear:cytoplasmic ratios arranged in sheets and loosely cohesive clusters with streaming erythrocytes and neutrophils in the background. Neoplastic cells were 13-25 μm in diameter and were round to cuboidal with variably distinct borders. Based on the signalment, anatomic location, and cytologic findings, differential diagnoses included salivary adenocarcinoma, squamous cell carcinoma, and mucoepidermoid carcinoma. The cow was euthanized and a necropsy was performed. The primary neoplasm arose from the left parotid salivary gland and meastatic tumor was found in the regional lymph nodes and lung. Histologically, the tumor was composed of anastomosing and irregular solid islets surrounded by scant stroma. Cells were negative for periodic acid-Schiff (PAS), PAS-diastase, and Alcian blue pH 2.5 stains, used to detect mucin. On immunohistochemical analysis, neoplastic luminal salivary gland cells expressed cytokeratin, but not S100, α-smooth muscle actin, or vimentin. Peripheral cells of neoplastic islets were immunoreactive for p63. The final diagnosis was nonsecretory adenocarcinoma of the parotid salivary gland.

Mucinous Adenocarcinoma of Minor Salivary Gland: Case Report and Literature Review

Mucinous adenocarcinoma (MAC) is a glandular tumor characterized by large pools of extracellular mucin. The tumor can arise as a primary tumor of the major salivary glands. However, its occurrence is exceedingly rare and has only recently been recognized. Only few cases in the major salivary glands have been reported. This report is an additional case of MAC with origin in minor salivary gland at the oral floor. Immunohistochemical analysis of the tumor for cytokeratins 7, 8, 10, 13, 14, 18 e 20, vimentin, SMA, CEA, EMA, p53, ki-67 e histochemical analysis for PAS, Alcian blue e mucicarmin was performed. Predominantly, the tumor expressed cytokeratins 7, 18 and 20 that are commonly found in simple epithelia. Therefore, was observed positivity to PAS, Alcian blue and mucicarmin. No other cancer has been detected. The tumor is considered to be a primary mucinous adenocarcinoma, being the twenty-third case in minor salivary gland reported in the literature and the fourth MAC located in the mouth floor.

A massive basal cell adenocarcinoma of the palatal minor salivary gland that progressed into the pterygopalatine fossa

Basal cell adenocarcinoma (BCAC) is a rare malignant neoplasm in the salivary glands and BCAC of the minor salivary glands is exceedingly rare. Only nine cases of palatal BCACs of the minor salivary gland have been reported. BCAC is a low-grade malignant tumour which shares many histologic characteristics with basal cell adenoma. Histological differentiation between the two is difficult and they are often discriminated only by invasion of local structures or by perineural or vascular invasive figures. The authors describe the case of a 69-year-old man with a massive BCAC of a palatal minor salivary gland that progressed into the nasal cavity and pterygopalatine fossa and was treated by a subtotal maxillectomy. This is a highly locally advanced case which required a wider surgical excision range than other previously reported BCAC cases of the palatal minor salivary glands. In this case, the proper diagnosis could not be made by local biopsy alone. It should be kept in mind that it may be difficult to distinguish BCAC from basal cell adenoma by microscopic examination of biopsy specimens alone.

Signet ring carcinoma parotid gland: A case report

Signet ring adenocarcinoma is a recently characterized entity occurring in the minor salivary glands. All reported cases have occurred in minor salivary gland. Pure signet ring adenocarcinoma of a major salivary gland has not been reported in the literature. A 38-year-old woman presented with a mass in the parotid region. Microscopy showed signet ring cells positive for mucicarmine. Immunohistochemistry showed cytokeratin and focal smooth muscle actin (SMA) positivity; an exhaustive search for primary elsewhere did not reveal any suspicious focus. A diagnosis of low-grade signet ring adenocarcinoma of the parotid gland was made. On 6-month follow-up the patient was alive and well. The present case highlights a rare occurrence of this tumor in the parotid gland, which until now was labeled as a tumor exclusive to minor salivary glands. Thus this entity should be kept as a differential while investigating mucinous tumors of parotid.

Head and Neck Pathology

Most malignant tumors in the head and neck are conventional keratinizing squamous cell carcinomas, and their microscopic diagnosis usually pose little challenge for pathologists. However, other conditions including rare malignancies can be encountered so infrequently that diagnosis or grading may be challenging. This issue of Pathology Case Reviews attempts to answer some of the more common questions that pathologists ask of their colleagues with an expertise in oral and/or head and neck pathology. These include the diagnosis and grading of oral epithelial dysplasia, the differential diagnosis of basaloid squamous carcinoma, and the relevance of HPV infection in squamous cancer of the oropharynx. Complementary articles discuss the diagnosis and grading of mucoepidermoid carcinoma, the clinical and pathologic features of salivary duct carcinoma, the diagnostic criteria of parathyroid carcinoma, and the microscopic and immunophenotypic features of marginal zone (MALT) lymphoma of the parotid gland. The diagnosis and terminology of precursor lesions to carcinomas of the upper aerodigestive tract is a challenging area for many pathologists because of the subtle microscopic features that form the basis of grading. This area is important because grading often guides clinical management for patients with premalignant disease. In their article, Drs Speight and Torres-Rendon present a case of squamous dysplasia of the oral tongue that progressed to squamous cell carcinoma. They clarify the clinical presentation of oral epithelial dysplasia and provide terminology and the histologic criteria for grading. The practical differential diagnosis and clinical management of oral epithelial dysplasia is also covered. Mucoepidermoid carcinoma is the most common primary malignancy of the salivary glands. Microscopic grading seems to play an important role in treatment selection and patient prognosis, and yet no common grading system has been agreed on. Drs Griffith and Seethala present a case of mucoepidermoid carcinoma arising in a minor salivary gland of the buccal mucosa. They present the differential diagnosis for mucoepidermoid carcinoma and then compare competing microscopic grading systems, problems in their application, and the clinical significance of grading. Salivary duct carcinoma is a rare, high-grade adenocarcinoma of the major salivary glands with a poor prognosis. Despite the distinctive cytologic and histologic features of this tumor and its resemblance to apocrine-type ductal carcinoma of the breast, salivary duct carcinoma can be mistaken for several other high-grade malignancies including mucoepidermoid carcinoma. We present a case of salivary duct carcinoma of the parotid gland and discuss the diagnostic features in fine needle aspirate and histologic samples, including the important role immunohistochemical assessment plays in establishing the diagnosis. Given the prevalence of primary hyperparathyroidism and the routine nature of parathyroid specimens in surgical pathology, a clear understanding of the diagnostic criteria for parathyroid carcinoma is required. Drs Khanafshar and van Zante discuss a case of parathyroid carcinoma, present the diagnostic criteria for a diagnosis of carcinoma and the diagnostic category of atypical adenoma. The applicability of a limited panel of immunostains is additionally reviewed. Another challenging area of head and neck pathology is the diagnosis of marginal zone (MALT) lymphoma, especially given the overlapping findings between long-standing autoimmune sialadenitis and MALT lymphoma. Drs McAlhany, Etzell, and Treseler present a case of MALT lymphoma of the parotid and discuss the histologic features, immunophenotype, and differential diagnosis. Recent advances in the understanding of the etiology of squamous cell cancer of the head and neck has shown that this group of tumors is made up of distinct subtypes with unique biological and histologic features. It has now been established that most squamous cell carcinomas arising in the oropharynx (base of tongue and lingual tonsils) are etiologically associated with oncogenic strains of human papillomavirus (HPV) rather than tobacco and alcohol, the traditional risk factors for head and neck cancer. Many HPV-associated squamous cell carcinomas are nonkeratinizing with a basaloid appearance. In their article, Drs Mills, Stelow, and Mills discuss the diagnosis of basaloid squamous cell carcinoma and highlight the broad differential that must be considered when a basaloid or small cell malignancy is encountered in the head and neck region. Finally, given that treatment paradigms may soon rely on pathologists to differentiate HPV-driven tumors and HPV-negative tumors, pathologists should make an effort now to understand the typical clinical presentation and histology of HPV-associated squamous cell carcinoma. A basic understanding of the indications for and limitations of immunohistochemistry for p16 and in situ hybridization for the identification of high-risk HPV is also required. The final article in this journal is an orientation to HPV-associated squamous cell carcinoma of the oropharynx and provides practical advice on how to evaluate and report squamous cancers of the oropharynx and the clinical implications of the diagnosis.FIGUREFIGURE

The Potential Role of MT and Vimentin Immunoreactivity in the Remodeling of the Microenvironment of Parotid Adenocarcinoma

A tumor stimulates the remodeling of its microenvironment in order to control and accelerate its own growth and to initiate metastases. To create metastases the tumor cells must first acquire the ability to detach from the main tumor and to adhere to, invade, and degrade the adjacent extracellular matrix. The cells must then be able to enter the lumen of the vessels where they home the distant tissues and organs by forming secondary tumors. The acquisition of this phenotype is related to the phenomenon of epithelial-to-mesenchymal transition. On the molecular level, this process is typified by a change in the expression of epithelial markers and by the enhancement of the expression of mesenchymal markers like vimentin that are responsible for cell migration and invasion. Metallothioneins have been shown to help protect against apoptosis. The expression of MT by tumor cells plays an important and complex role not only because of its pro-proliferative, anti-apoptotic activity, but also because it inhibits the immune response. The aim of the present study was to evaluate the immunoreactivity of vimentin and MT in the salivary gland adenocarcinoma and its stroma in order to observe the phenomenon of stromal remodeling. The tissue samples of salivary gland adenocarcinomas and their stromas and the palatine tonsils which constituted the reference group were obtained during routine surgical procedures. The immunoreactivity of vimentin, metalothionein, CD56, CD57 antigens was evaluated by the immunohistochemistry method in 30 tissue samples of parotid adenocarcinoma. The patient’s consent was obtained in each case. A statistically significantly higher level of MT immunoreactivity was observed in the adenocarcinoma tissue slides than in either the stromal slides or the reference slides while no differences in MT immunoreactivity were detected when the stroma and reference tissue slides were compared. A statistically significantly higher vimentin immunoreactivity level was identified in the tumor microenvironment tissue slides than in the tumor tissue slides, and a statistically significantly higher level of vimentin immunoreactivity was identified in the tumor microenvironment slides than in the slides of the reference tissue, while no differences were identified between the adenocarcinoma tissue slides and the reference slides with respect to vimentin immunoreactivity. A statistically significantly higher number of CD56- and CD57-expressing cells were identified in the reference tissue slides than in either the adenocarcinoma or stromal slides. In conclusion, the stroma of salivary gland adenocarcinoma in this study has been characterized by remodeling. The remodeling is represented by the expression of both vimentin and MT and by a deficit of CD57- and CD58-expressing cell infiltration. This situation would seem to be the result of immune tolerance for the tumor developing within the tumor microenvironment. Furthermore, the presence of MT and vimentin immunoreactivity in the fibroblasts of the tumor stroma may constitute a marker of active tissue remodeling.

Polymorphous low-grade adenocarcinoma of salivary glands: report of nine cases

IntroductionPolymorphous low-grade adenocarcinoma is the second most common type of malignant tumour in the minor salivary glands. Its occurrence in major salivary glands is rare. It is characterized by architectural diversity, a uniform cytological, and a low degree of malignancy.Materiel and methodsWe have done a retrospective histopathological review of 200 benign and malignant salivary gland tumours to list all the cases of polymorphous low-grade adenocarcinoma of salivary glands, in the Laboratory of Anatomopathology specialities hospital for five years.ResultsWe identified nine cases of polymorphous low-grade adenocarcinoma of salivary glands. The average age of the patients, five women and four men, was 58.3 years. The tumours were 30 to 100 mmlarge; five were in minor salivary glands, and four in the parotid. Histologically, all the tumours had a polymorphous architectural pattern. The tumour cells were uniform, and showed a low mitotic count.ConclusionThe principal interest in studying this tumour is its favourable prognosis, with a low degree of malignancy, and a rare tendency to recur or metastasize.

Cribriform adenocarcinoma of the base of the tongue and low-grade, polymorphic adenocarcinomas of the salivary glands

Low-grade, polymorphic adenocarcinomas occur mainly in females and are usually associated with the small salivary glands of the palate. The tumors are malignant, but not aggressive. Regional neck as well as distant metastasis is rare and the mortality rate is low. Cribriform adenocarcinoma of the salivary glands is a rare tumor, currently ranked among low-grade, polymorphic adenocarcinomas of the salivary glands. However, it differs from carcinomas in this group as it metastasizes to the cervical lymph nodes and exhibits frequent primary localization in the small salivary glands at the base of the tongue. Despite the tendency to metastasize, patient prognosis remains favorable. A case of a 72-year-old woman with neck metastases of cribriform adenocarcinoma, of unknown primary origin, is reported. The primary tumor origin was ultimately determined using nuclear magnetic resonance, histological verification was difficult due to the presence of an intact mucosal cover over the tumor. Cribriform adenocarcinoma is known to have a number of characteristics in common with a typical low-grade, salivary gland adenocarcinoma. However, in contrast to low-grade adenocarcinomas, the tumor presented with neck lymph node metastasis.

Cytoplasmic expression of survivin is an independent predictor of poor prognosis in patients with salivary gland cancer

The expression of the inhibitor of apoptosis protein survivin has been shown to be a significant prognostic indicator in various human cancers. The aim was to assess its expression and prognostic value in salivary gland adenocarcinoma and muco-epidermoid carcinoma. Survivin expression was analysed in 48 patients with parotid gland cancer (21 muco-epidermoid, 27 adenocarcinomas) by means of immunohistochemistry. The experimental findings were correlated with clinicopathological and survival parameters. A high cytoplasmic expression of survivin was found in 30% of the examined tumours without any significant correlation with the patients' clinicopathological characteristics (P > 0.05). Within all patients, the estimated overall survival rate of muco-epidermoid carcinomas was significantly better than that of adenocarcinomas (P = 0.013). A high cytoplasmic survivin expression significantly indicated a poor 5-year disease-free survival rate compared to patients with a low cytoplasmic survivin expression in the whole group (P = 0.001) and in adenocarcinomas (P = 0.004). In a multivariate analysis, a high cytoplasmic survivin expression was the only independent prognostic indicator for a significantly poorer 5-year disease-free survival rate (P = 0.001). The correlation between cytoplasmic survivin expression and survival in salivary gland malignancies might make this an effective tool in patient follow-up, prognosis and targeted therapy in future.

Signet-ring cell (mucin-producing) adenocarcinoma of minor salivary glands: report of a case

Salivary gland tumors account for a significant group of head and neck neoplasms. Signet-ring cell (mucin-producing) adenocarcinoma of minor salivary glands was described by Ghannoum and Freedman in 2004. We report a case of this extremely rare minor salivary gland neoplasm in an 18-year-old male. To our knowledge, this patient is the youngest to ever be reported having this tumor.

Toll-like receptor 5 activation promotes migration and invasion of salivary gland adenocarcinoma

Toll-like receptor (TLR) signaling has been found to be closely associated with tumor development. The aim of this study was to examine whether activation of TLRs promote migration and invasion of salivary gland adenocarcinoma. TLR expression in SGT and HSG cells was examined by RT-PCR. Wound scratch and chemotaxis cell migration assay were performed. Invasiveness was determined by Matrigel invasion assay. All the tested TLRs including TLR1, TLR2, TLR4, and TLR5 and myeloid differentiation factor-2 (MD-2) were expressed on SGT and HSG cells. Treatment of flagellin, but not Pam(3) CSK(4) and LPS, led to the production of IL-6 and IL-8, suggesting TLR5 is functional in both cells. Stimulation by flagellin also accelerated wound closure of SGT and HSG cells in a dose-dependent manner. In addition, flagellin promoted migration and invasion ability of SGT cells. Blocking of TLR5 using antibody restored the promoting effect of flagellin on migration and invasion of SGT cells. These findings suggest that TLR5 activation by flagellin can promote migration and invasion of salivary gland adenocarcinoma.

The Involvement of RCAS1 in Creating a Suppressive Tumor Microenvironment in Patients with Salivary Gland Adenocarcinoma

The tumor microenvironment is the tissue that determines the growth and progression of the tumor as well as its ability to initiate metastases. The aim of the present study has been to evaluate the role of RCAS1 in creating the suppressive tumor microenvironment in cases of parotid adenocarcinoma. The tissue samples of salivary gland adenocarcinomas and their stroma and the palatine tonsils which constituted the reference tissue sample group were obtained during routine surgical procedures. The immunoreactivity of RCAS1, CD3, CD25, CD68, CD69, and Foxp3 antigens was then evaluated by using the immunohistochemistry method. The patient’s consent was obtained in each case. A statistically significantly higher RCAS1 immunoreactivity level was found in the adenocarcinoma tissue samples in comparison to that found in the stromal tissue samples. A statistically significantly higher RCAS1 immunoreactivity was also identified in the adenocarcinoma tissue samples derived from patients who had lymph node metastases in comparison to patients without such metastases. Additionally, we observed the presence of RCAS1-positive macrophages in the stromal tissue samples. The infiltration of CD68-positive cells was significantly stronger in the adenocarcinoma and stromal tissue slides than in the reference group tissue slides; moreover, the infiltration was a good deal more prominent in the stromal tissue than in the adenocarcinoma tissue. The CD68 immunoreactivity levels in both the tumor and stromal tissue samples were found to be significantly higher in those patients who had lymph node metastases than in the patients without such metastases. Additionally, the infiltration of CD3- and CD25-positive cells was more prominent in the reference tissue slides than in the adenocarcinoma and stromal tissue slides, and was stronger in the adenocarcinoma tissue than in the stromal tissue. Furthermore, the infiltration of Foxp3-positive cells was seen exclusively in the stroma whereas it was not even detected in the adenocarcinoma tissue. Lastly, the Foxp3-positive cell infiltration was more prominent in the stromal tissue than in the reference group tissue. The present study demonstrates that RCAS1 expression by both tumor cells and tumor-associated macrophages may participate in creating the immunosuppressive microenvironment in parotid gland adenocarcinoma, thus promoting tumor development as well as metastases.