RESUMEN
BACKGROUND: Epithelial to mesenchymal transition promotes cell adhesion loss, enabling invasion and metastasis. MicroRNAs are a class of small non-codifying RNAs that regulate gene expression. OBJECTIVES: The aim of this study was to evaluate the expression of microRNAs that could regulate the expression of EMT factors in salivary gland tumors (SGTs). METHODS AND RESULTS: The expression of microRNAs miR-9, miR-34a, miR-101, miR-138, miR-155, and miR-200c-described in the literature to target EMT factors-was evaluated by Real-time RT-PCR (qPCR) in pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) samples. Bioinformatics tools were applied to identify miR targets and immunohistochemistry was used to examine the expression of the proteins E-cadherin, Twist, ZEB-1, ß-Catenin, and c-Kit. Comparing miR expression among SGT types, we observed increased expression of miR-9, and miR-138 in PAs, and increased miR-155 expression in MECs. Low-grade MECs exhibited increased miR-155 expression (p = 0.032). MECs that generated lymph node metastases had increased miR-200c levels (p = 0.018). MECs tended to have decreased expression of EMT-related proteins when compared to the other SGT types (c-Kit p < 0.001, Twist p = 0.014, and ZEB p = 0.012). Notably, increased c-Kit expression was associated with the presence of perineural infiltration in ACC (p = 0.050). CONCLUSIONS: This study provides evidence of alterations in the expression of EMT-factors regulating miRs, especially of miR-9, miR-138, miR-155, and miR-200c. No significant relationships were found between the expression of these miRs and proteins associated with EMT in SGTs.
Asunto(s)
MicroARNs , Neoplasias de las Glándulas Salivales , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de las Glándulas Salivales/genéticaRESUMEN
OBJECTIVES: The aim of this study was to analyze the expression of CD24, CD44, CD133, ALDH1, CD29 (integrin-ß1), and Ki-67 in squamous cell carcinoma of the oral cavity and oropharynx. STUDY DESIGN: Fifty-two tumors and 21 metastatic lymph nodes were evaluated by using immunohistochemistry. RESULTS: Seven of 52 cases (13.5%) showed positive cytoplasmic staining of aldehyde dehydrogenase 1; integrin-ß1 was expressed in 45 of 50 cases (90%); 30 of 52 cases (57.7%) had positive membranous staining of CD44; CD24 was expressed in 44 of 50 cases (88%); and three of 52 cases (5.8%) stained positively for membranous CD133. Median proliferation rate, measured by Ki-67, was 37.1% for tumors. Five-year cancer-specific survival rates for the CD44-negative and CD44-positive groups were 74% and 38%, respectively, although this difference did not reach statistical significance (P = .052). CONCLUSIONS: Our study demonstrated the expression of putative stem cell markers in squamous cell carcinoma of the oral cavity and oropharynx, with participation of CD44-positive cells in association with poor survival outcome.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias de la Boca/metabolismo , Neoplasias Orofaríngeas/metabolismo , Células Madre/metabolismo , Antígeno AC133/metabolismo , Familia de Aldehído Deshidrogenasa 1 , Antígeno CD24/metabolismo , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Receptores de Hialuranos/metabolismo , Inmunohistoquímica , Integrina beta1/metabolismo , Isoenzimas/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Estadificación de Neoplasias , Neoplasias Orofaríngeas/patología , Retinal-Deshidrogenasa/metabolismo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is primarily a locoregional disease in which the cervical lymph nodes are the chief site of metastasis. The purpose of this study was to examine the relationship between lymphangiogenesis and clinicopathological aspects of HNSCC and its metastasis. METHODS: Fifty-two patients with HNSCC and metastatic lymph nodes from 21 of these subjects were analyzed by immunohistochemistry. RESULTS: The HNSCC samples were predominantly negative for vascular endothelial growth factor (VEGF)-C, VEGF-D, and vascular endothelial growth factor receptor (VEGFR)3. There was an association between the density of lymph vessels (measured by D2-40 staining) in the lymph nodes and advanced-stage tumors. There was no link between the expression of these proteins and survival rates. CONCLUSION: Although lymphatic spread is a significant event in the progression of HNSCC, the expression of VEGF-C, VEGF-D, and VEGFR3 does not correlate with clinicopathological characteristics, suggesting that other signaling pathways mediate lymphangiogenesis in HNSCC.