COMPARISON OF BENIGN AND MALIGNANT ENDOMETRIAL LESIONS FOR THEIR P53 STATE, USING IMMUNOHISTOCHEMISTRY AND TEMPERATURE-GRADIENT GEL-ELECTROPHORESIS

The aim of this study was to evaluate the presence and distribution of p53 alterations in pure endometrioid adenocarcinomas (n=120) of diffe rent grades and stages, as opposed to normal endometrium (n=13) and va rious risk groups of hyperplasia (n=39). All samples were initially an alysed by immunohistochemistry with the monoclonal antibody Ab-6. Norm al endometria were negative. With increasing degrees of malignancy, th e number of cases with p53 accumulation rose and ranged from 9% to 18% in hyperplasia, through 25% in low-grade carcinomas (G1), to 69% in h igh-grade carcinomas (G3). This increase was also seen when comparing tumours by stage. Of carcinomas in stage IA, only 17% showed p53 immun ostaining, in contrast with 72% in stage IC. Of this material, 34 carc inomas and 8 hyperplasias were analysed for p53 mutations in exons 5-8 by means of polymerase chain reaction and temperature-gradient gel el ectrophoresis (TGGE). In none of 5 hyperplasia and 6 of 12 carcinomas showing p53 accumulation by immunohistochemistry, p53 mutations were d etected by TGGE. In contrast, 4 of 22 carcinomas harboured mutant p53 but were negative by immunohistochemistry. Immunohistochemical and mol ecular investigations revealed that p53 alterations are related to the standard prognostic markers of endometrial cancer, i.e. grading and s taging. TGGE, an indirect screening procedure for p53 mutations, is us ed to detect the type of p53 alteration and may provide additional ins ight into the complex figure of p53 abnormalities in the development a nd progression of malignant endometrial lesions.