RESUMEN
Recently, it has been reported that deregulation of the receptor activator of NFkB ligand (RANKL)/RANK signaling axis results in salivary gland tumor development in a mouse transgenic model. The aim of this study was to ascertain RANKL and RANK protein expression in a series of primary parotid gland carcinomas and to correlate it with clinicopathologic parameters. Formalin-fixed paraffin-embedded tumor samples from 46 consecutive cases of parotid gland carcinoma were selected for this study. For comparison, we examined a group of 40 randomly chosen parotid gland adenomas, including 20 pleomorphic adenomas, 10 myoepitheliomas, and 10 Warthin tumors. Immunohistochemical analysis for RANK and RANKL was conducted on tissue microarrays. Overall, 33 carcinomas (71.7%) were scored as positive for RANK and 25 (54.3%) for RANKL. The expression of both RANK and RANKL was significantly higher in carcinomas than in adenomas as only 6 (15%) adenomas were positive for RANK, and RANKL was negative in all benign tumors (P<0.001 for both, Fisher exact test). Some histologic types, including salivary duct carcinoma, mucoepidermoid carcinoma, and carcinoma ex-pleomorphic adenoma presented a high frequency of RANK and RANKL expression. No significant correlation was observed between RANK/RANKL expression and clinical parameters. Our study indicates that the expression of RANK and RANKL in parotid gland neoplasms is associated with the acquisition of a malignant phenotype and this pathway may represent an attractive therapeutic target in patients with parotid gland carcinomas.
Asunto(s)
Adenoma Pleomórfico , Carcinoma Mucoepidermoide , Regulación Neoplásica de la Expresión Génica , Mioepitelioma , Proteínas de Neoplasias/biosíntesis , Neoplasias de la Parótida , Ligando RANK/biosíntesis , Receptor Activador del Factor Nuclear kappa-B/biosíntesis , Neoplasias de las Glándulas Salivales , Adenoma Pleomórfico/metabolismo , Adenoma Pleomórfico/mortalidad , Adenoma Pleomórfico/patología , Adulto , Anciano , Carcinoma Mucoepidermoide/metabolismo , Carcinoma Mucoepidermoide/mortalidad , Carcinoma Mucoepidermoide/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mioepitelioma/metabolismo , Mioepitelioma/mortalidad , Mioepitelioma/patología , Glándula Parótida/metabolismo , Glándula Parótida/patología , Neoplasias de la Parótida/metabolismo , Neoplasias de la Parótida/mortalidad , Neoplasias de la Parótida/patología , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/mortalidad , Neoplasias de las Glándulas Salivales/patología , Tasa de SupervivenciaRESUMEN
PURPOSE: Adenoid cystic carcinoma (ACC) is a uncommon salivary malignant tumor. Our aim was to review our experience with parotid ACC, to identify clinical-pathological parameters predictive for outcome. MATERIALS AND METHODS: We retrospectively reviewed 228 patients affected by parotid gland carcinomas surgically treated at our Institution. Forty-four ACC were included in this study. Multivariate analysis risk models were built to predict recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and disease free survival (DFS). RESULTS: Twenty-one patients (47.7%) died from ACC and 2.3% for other causes. The 41% presented local-regional recurrence, with a regional-RFP rate of 93%, and the 34% reported distant metastases (DM). The five and ten-year OS rates were 74% and 50%, respectively. CONCLUSIONS: Recurrences were mainly influenced by the presence of perineural invasion and nerve paralysis, whilst female gender and age<50 were predictors for good prognosis.