P53 ALTERATIONS IN THYMIC EPITHELIAL TUMORS

The prognosis of thymic epithelial rumours depends on malignant behavi our that cannot always be predicted on histological grounds. This stud y aimed at identifying a molecular marker that would be useful in over coming the drawbacks of histopathology. Forty-four thymic epithelial r umours were analysed for alterations of the tumour suppressor gene p53 using immunohistochemistry (antibodies D0-1 and CM-1) and PCR-based s ingle-strand conformation polymorphism and DNA sequencing. Histologica l and clinical evaluation and also p53 analysis revealed three major t umour groups: non-organotypic thymic carcinomas with frequent p53 alte rations (7/9) and occurrence of p53 gene mutations (2/9); malignant th ymomas with frequent p53 alterations but without p53 gene mutations (1 1/18); and benign thymomas with rare p53 alterations and without p53 g ene mutations (2/17). In non-organotypic thymic carcinomas p53 was det ected with both antibodies. In contrast, thymomas lacked immunoreactio n with D0-1 suggesting alteration of the antibody-binding site. Overal l immunohistochemical results correlated with clinical stages (P < 0.0 1), pathohistology (P < 0.01), and survival times (P < 0.05). We consi der immunohistochemical p53 detection to be a useful new prognostic fa ctor for the evaluation of thymic epithelial rumours.