GERM-CELL TUMORS OF THE TESTIS OVEREXPRESS WILD-TYPE P53

Several recent studies have suggested that testicular germ cell tumors express high levels of wild-type p53 protein, To clarify and confirm this unexpected result, we have investigated seminomatous and nonsemin ontatous germ cell tumors at the genomic, mRNA, and protein levels. Th irty-five tumors were examined for p53 overexpression using antibodies directed against the p53 (PAb1801, PAb240, and CMI), mdm2 (IF2), and p21(Waf1/Cip1) (EA10) proteins, Thirty-two tumors were screened for p5 3 mutations by single-strand conformation polymorphism analysis. Eight een tumors were screened with a functional assay that tests the transc riptional competence of human p53 protein expressed in yeast On frozen sections, 100, 65, 35, 73, and 0% of tumors reacted with the CMI, PAb 240, PAb1801, IF2, and EA10 antibodies, respectively, No p53 mutations were detected by single-strand conformation polymorphism or by functi onal assay. The fact that ma?ty tumors overexpress wild-type p53 hut n ot mdm2 rules out mdma overexpression as a general explanation for the presence of wildtype p53 in these tumors. The absence of p21 overexpr ession suggests that p53 may be unable to activate transcription of cr itical target genes, which may explain why the presence of wild-type p 53 is tolerated in this tumor type, although the mechanism for this tr anscriptional inactivity remains to be established.