RESUMO
Pleomorphic adenoma (PA) is the most common salivary gland neoplasm and, although mostly benign, recurrences, being called recurrent pleomorphic adenoma (RPA) and malignant transformation to carcinoma ex pleomorphic adenoma (CXPA), do occur. Recently, attention has been focused on molecular targeted cancer therapy in various tumors, including salivary gland tumors. The aim of this study was to investigate the role of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) in PA, RPA, and CXPA. In total, 20 cases of PA, 18 of RPA, and 7 cases of CXPA were immunohistochemically studied for ER, PR, and HER-2. For evaluation of ER and PR, only nuclear expression and greater than 10% positive cells were regarded as cutoff criteria. HER-2 was evaluated semiquantitatively and graded from 0 to 3+. HER-2 amplification was assessed by chromogenic in situ hybridization (CISH). Tumors were negative for ER, PR, and HER-2 in all cases of PA and RPA. A case of CXPA showed moderate and complete membranous staining, and 6 cases were negative. HER-2 amplification was not observed in any case. In conclusion, the lack of ER, PR, and HER-2 expression in PA, RPA, and CXPA suggests that these proteins are not involved in progression, recurrence, or malignant transformation of PA.
RESUMO
Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and while mostly benign, recurrences (RPA) and malignant transformation to carcinoma ex-PA (CXPA) do occur. Cell cycle proteins important in its tumorigenesis have been studied as markers for PA with a high risk of RPA or CXPA. The aim of the present study was to investigate cell cycle markers p-16, cyclin D1, CDK4, E2F, and retinoblastoma (Rb) in this context. Expression of p16, cyclin D1, E2F, CDK4, and Rb was studied by immunohistochemistry in 24 cases of PA, 21 of RPA, and 2 of CXPA. The presence of HPV was assessed by in situ hybridization. Immunostaining for p16 and cyclin D1 was negative or weakly positive in most cases of PA while strongly positive in the majority of RPA and both CXPA cases. Staining for Rb and CDK4 was either negative or weakly positive in PA, RPA, and CXPA. Expression of E2F was stronger in RPA and CXPA than in PA. Nuclear reactivity for HPV was not observed in any case. In conclusion, the strong staining for p16, cyclinD1, and E2F in RPA and CXPA, while weak or negative in PA, suggests that these proteins might be involved in recurrence and malignant transformation of PA.