p53-Alterations in Thymic Epithelial Tumors
On the basis of histopathology thymic epithelial tumors are subdivided into organotypic thymomas and non-organotypic thymic carcinomas. Although thymomas do not exhibit gross cellular atypia they may behave clinically malignant. To warrant the pathologic detection of malignancy in thymic epithelial tumors the tumor suppressor p53 was analysed whose alterations are known to be a common event during carcinogenesis. The analysis of the p53-protein was carried out by immunohistochemistry using a monoclonal (D0–1) and a polyclonal antibody (CM-1). The p53-gene was analysed by PCR-SSCP of the exons 5–8 and DNA-sequencing. In thymomas including well-differentiated thymic carcinomas p53-protein alterations were detected with the polyclonal antibody CM-1 but not with the monoclonal antibody D0–1, and no mutations were found in exons 5–8 of the p53-gene. In contrast, in non-organotypic thymic carcinomas mutant p53-protein was detected with both the monoclonal and the polyclonal antibodies. The integration of morphological, clinical and p53-analysis data identified three major groups of thymic epithelial tumors: (1) benign thymomas with a low incidence of p53-protein alterations; (2) malignant thymomas (including well-differentiated thymic carcinomas) with a high incidence of p53-protein alterations; in both thymoma groups no p53-gene mutations were found at the genetic level (exons 5–8); (3) non-organotypic thymic carcinomas with a high incidence of p53-protein alteration, simultaneous occurrence of p53-gene mutations and 17p LOH. We consider the immunohistochemical analysis of the p53-protein not only a new useful tool in the pathological evaluation of thymic epithelial tumors. p53-protein alterations are also correlated with shortened survival times and their detection can therefore be used for prognostical judgement. The failure of the monoclonal antibody D0–1 to detect altered p53-protein in thymomas points to an epitope concealing event of the D0–1 binding site in these tumors.
KeywordsThymic Carcinoma Invasive Thymoma Malignant Thymoma Missense Point Mutation Aminoacid Change
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