Expression of apoptosis-related markers and HER-2/neu in thymic epithelial tumours

Aims: To correlate the expression of a series of apoptotic and oncogene markers (including p53, Bcl-2, BAX, Bcl-X_L, p21^WAF.1/CIP1, cyclin D1, HER-2/neu) in thymic epithelial tumours with histological type, stage and resectability and to determine whether the information on HER-2/neu would be valuable in identifying patients who are eligible for anti-HER-2/neu treatment. Methods and results: Immunohistochemical stains were performed on 16 cases of non-neoplastic thymus, 63 thymomas and 17 thymic carcinomas. Fluorescence in-situ hybridization (FISH) for HER2 was performed to validate the gene amplification. Eighteen thymomas were positive for p53 and 14 of them were low-expressors, with positive cells below 10%. All thymic carcinomas revealed over-expression of p53 with positive cells either between 10% and 50% or >50%. The expression of p53 correlated with histological type and stage in thymoma. In both thymoma and thymic carcinoma, there was a statistically significant correlation between p53 status and resectability, with low expressors having a higher likelihood of being resectable. Thymic carcinomas, regardless of the histological subtypes, uniformly expressed Bcl-2, while thymomas showed no or only weak cytoplasmic immunoreactivity. Most thymomas and thymic carcinomas were negative for Bcl-X_L, p21^WAF.1/CIP1 and cyclin D1. The expression of BAX was inconsistent among different histological types. Nine thymic carcinomas revealed membranous positivity for HER-2/neu. but no HER2 gene amplification could be demonstrated by FISH in any of the cases. Conclusions: p53 and Bcl-2 are more implicated in the development of thymic carcinoma than thymoma. The higher level of p53 expression and the strong immunopositive pattern of Bcl-2 in thymic carcinomas have potential value in the differential diagnosis and prediction of aggressiveness and resectability. On account of the absence of HER2 amplification, patients would probably not benefit from anti-HER-2/neu treatment.