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BackgroundSalivary Glands Malignant Neoplasms (SGMNs) account for 3-6% of head and neck cancers and 0.3% of all cancers. Tumor cells that express CD44 and CD24 exhibit a stem-cell-like behavior. CD44 is the binding site for hyaluronic acid, and CD24 is a receptor that interacts with P-selectin to induce metastasis and tumor progression. The present study aims to evaluate the expression of CD44 and CD24 on SGMNs and correlated these data with several clinicopathologic features.MethodsImmunohistochemical stains for CD44 and CD24 were performed on tissue microarrays containing SGMN samples from 69 patients. The CD44, CD24 and CD44/CD24 expression phenotypes were correlated to patient clinicopathologic features and outcome.ResultsCD44 expression was associated with the primary site of neoplasm (p = 0.046). CD24 was associated with clinical stage III/IV (p = 0.008), T stage (p = 0,27) and lymph node (p = 0,001). The CD44/CD24 profiles were associated with the primary site of injury (p = 0.005), lymph node (p = 0.011) and T stage (p = 0.023). Univariate analysis showed a significant relationship between clinical staging and disease- free survival (p = 0.009), and the overall survival presents relation with male gender (p = 0.011) and metastasis (p = 0.027).ConclusionIn summary, our investigation confirms that the clinical stage, in accordance with the literature, is the main prognostic factor for SGMN. Additionally, we have presented some evidence that the analysis of isolated CD44 and CD24 immunoexpression or the two combined markers could give prognostic information associated to clinicopathologic features in SGMN.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1284611098470676.

Objective: Salivary gland (SG) development is based on branching morphogenesis, in which programmed cell death has been proposed to play a role in cell signalling and organ shaping.In the mouse salivary gland apoptosis has been suggested to play a key role in lumen formation, removing the central cells of the epithelial stalks. Here we analyse the expression of several anti-and pro-regulators of apoptosis during human SG development in a range of developmental stages.Design: Foetal SGs obtained from the University of São Paulo were analysed by immunohistochemistry to assess the expression of apoptosis-associated proteins: caspases (caspase-6, -7, -9 and cleaved caspase-3), Bcl-2 family members (Bax, Bak, Bad, Bid, Bcl-2, Bcl-x and Bcl-xL), Survivin (BIRC5), Cytochrome C and Apaf-1.Results: Nuclear expression of Bax and Bak was identified in presumptive luminal areas at initial stages, while Bcl-xL showed the most relevant anti-apoptotic activity. Caspase-6, -7 and -9 were expressed during all stages, while interestingly cleaved caspase-3 showed no prominent expression, indicating that caspase-7 is the main effector. Apoptosome complex components Apaf-1 and Cytochrome C, as well as survivin were all positive in developing glands. Conclusions:The particular expression pattern of several apoptotic regulators in human SG development suggests the existence of a fundamental role for apoptosis during duct formation. The absence of Bad and Bid expressions indicates that the instrinsic pathway is more active then the extrinsic during human gland formation. The subcellular localisation of intrinsic-apoptosis proteins correlated with apoptotic activity, but also suggested additional non-apoptotic functions. Highlights: Caspase-7 is the main executioner caspase involved in human SG duct development  Consistent cytoplasmic expression suggest additional non-apoptotic functions  Intrinsic-type apoptotic pathway drives human SG development

Background Mucoepidermoid carcinoma is the most common malignant tumor of salivary glands. Apoptosis plays an important role in organogenesis of glandular structures, and aberrations of apoptotic mechanisms is associated with a wide array of pathologic conditions. Methods The immunoexpression of proteins associated with apoptosis and proliferation was evaluated in 40 mucoepidermoid carcinoma cases. Results Par‐4, Survivin, MUC1, PHLDA1, Fas, and Ki‐67 were predominantly expressed in mucoepidermoid carcinoma. FasL was rarely expressed, and Caspase‐3 expression was observed in almost 50% of the cases. SPARC expression was associated with low‐grade tumors, and Ki‐67 expression was associated with lymph node metastasis. Expression of Fas and decreased expression of Ki‐67 and Caspase‐3 were associated with better overall cancer‐specific survival rates. Conclusions The association of SPARC and Ki‐67 expression with pathological features and the association of Fas, Caspase‐3, and Ki‐67 with survival probabilities suggest that these proteins may be useful prognostic markers for mucoepidermoid carcinoma.

PA and stem cells share the expression of CD24 and CD44; their value as markers of neoplastic cell multipotency and the implications of their expression for tumour behaviour are yet to be determined.

BackgroundCD44 is the binding site for hyaluronic acid, and CD24 is a receptor that interacts with P‐selectin to induce tumor progression. Present study aims to evaluate CD44/CD24 expression on SGMNs and correlated these data with clinicopathologic features.MethodsImmunohistochemical stains for CD44/CD24 were performed on 69 SGMN samples. CD44/CD24 expression was correlated to patient clinicopathologic features and outcome.ResultsCD44 expression was associated with the primary site of neoplasm (p=0.046). CD24 was associated with clinical stage III/IV (p=0.008), T stage (p=0,27) and lymph node (p=0,001). The CD44/CD24 profiles were associated with the primary site of injury (p=0.005), lymph node (p=0.011) and T stage (p=0.023).Conclusionin summary, we have presented some evidence that the analysis of CD44/CD24 expression could give prognostic information associated to clinicopathologic features in SGMN.

Background: Salivary gland neoplasms are originated from the various salivary gland compartments and are histologically related to these structures. Several protein and molecular markers are employed in research and diagnosis in order to classify and understand histogenesis and other aspects of salivary gland neoplastic lesions. Pleomorphic adenoma is a benign salivary gland neoplasm composed by epithelial and myoepithelial cells and a complex stroma. Its varied structural and architectural aspects suggest the participation of stem cells in its composition. Additionally, pleomorphic adenoma originates from intercalated duct of salivary glands, a region reputed to host the regenerative/ stem-cell compartment of these glands. The present work investigated stem-cell markers (CD24, CD44) in pleomorphic adenoma and in specimens of developing human salivary glands using immunohistochemistry and real-time RT-PCR. Material and Methods: 101 cases of pleomorphic adenomas were used - 55 cases were FFPE and 60 specimens were fresh frozen tissue. From the total, 14 were pared (FFPE and frozen tissue). Salivary gland specimens dissected from 20 human foetuses were also included. Results: All cases of pleomorphic adenomas were positive for the stem-cell markers studied. Neoplastic luminal structures were positive for CD24. Modified myoepithelial cells were positive for CD44. In foetal salivary glands, these markers were restricted to the intercalated duct region. Increased expression of CD44 stem-cell marker was observed in pleomorphic adenoma specimens using real-time RT-PCR technique when compared to normal salivary gland controls. An specific expression pattern was not observed for CD24 when compared to the normal salivary gland tissue - in some cases of pleomorphic adenoma there was an increased expression of the protein, whilst in other cases the expression was decreased or normal-like. Conclusion: Pleomorphic adenoma cells share similar markers with stem-cells; it is not possible to confirm that neoplastic cells bear the same characteristics of multipotency. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5352. doi:1538-7445.AM2012-5352

Background: MicroRNAs (miRNAs) are a class of short noncoding RNAs, that regulate the gene expression by binding to the 3′ - untranslated region of target mRNAS and by blocking the translation or degradation of the mRNAs that mediate various pathophysiological process including the pathogenesis of diverse human cancers and important cellular functions such as proliferation, apoptosis, differentiation, and cell signaling. Salivary gland tumors are complex, due to their broad histological spectrum resulting from multiple tumor cell differentiation. We previously detected that the protein c-kit is involved in the process of salivary gland morphogenesis and tumorigenesis; other recent studies reported alterations in KIT gene in adenoid cystic carcinoma. The aim of the present study is to determine the expression of microRNAs targeting KIT in pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC), the most common benign and malignant salivary gland neoplasms, respectively, and that originate from the intercalated duct region. Material and Methods: Twenty-five pleomorphic adenoma, 14 adenoid cystic carcinoma and 10 non-neoplastic salivary gland samples were used and miRNA expression was evaluated by Real Time RT-PCR using TaqMan miRNA Assays (miR- 221 and 222). Results: Expression of miR-221 was detected in 13 CAC samples and 19 PA samples. In CAC, expression of miR-221 was downregulated in 4 out of 13 (30,77%) samples, upregulated in 4 out of 13 (30,77%) samples, and normal in 5 out of 13 (38,46%) samples. In PA, miR-221 expression was downregulated in 7 out of 19 (36,84%) samples, upregulated in 2 out of 19 (10,53%) samples, and normal in 10 out of 19 (52,63%) samples. Expression of miR-222 was detected in 14 CAC samples and 22 PA samples. In the majority of CAC samples, the expression of miR-222 was similar to that observed in non-neoplastic samples. In PA samples, expression of miR-222 was downregulated in 7 out of 22 (31,8%) samples, upregulated in 8 out of 22 (36,4%) samples, and normal in 7 out of 22 (31,8%) samples. Conclusion: The expression of miRNAs 221 and 222 do not present a definite pattern to discriminate PA from ACC. This might be due to different mechanisms involved in their tumor biology or due to their common site of origin (the intercalated duct) which could add some similar biological features to both neoplasms. Citation Format: Renata Carolina Fraga Ianez, Cláudia Coutinho-Camillo, Clóvis Pinto, Fernando Soares, Silvia Lourenço. miR-221 ans miR-222 expression in salivary gland tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4015. doi:10.1158/1538-7445.AM2015-4015