MDM2 AND P53 PROTEIN EXPRESSION IN THE HISTOLOGIC SUBTYPES OF ENDOMETRIAL CARCINOMA

The frequency of p53 protein overexpression differs among the histolog ic subtypes of endometrial carcinoma, from 21 to 48% in endometrioid c arcinoma but from 80 to 86% in papillary serous carcinoma Although p53 gene mutation can closely correlate with p53 protein overexpression i n papillary serous carcinomas, high expression of p53 protein may also occur without detectable gem mutation in endometrioid carcinomas, Bec ause MDM2 protein can bind mutant and wild-type p53 protein, we examin ed MDM2 and p53 protein expression in 27 endometrioid carcinomas and c ompared their expression patterns with those of 25 uterine papillary s erous carcinomas. We detected p53 protein in 14 (52%) of the 27 endome trioid carcinomas but in 21 (84%) of the 25 papillary serous tumors (P = 0.02). MDM2 expression was more commonly detected in the endometrio id carcinomas. Nineteen (70%) of the 27 cases showed expression compar ed with 9 (36%) of the 25 papillary serous carcinomas (P = 0.03). p53 Expression correlated closely with MDM2 expression in endometrioid car cinomas but not in the papillary serous carcinomas. In endometrioid ca rcinomas, MDM2 was detected in 13 (93%) of 14 p53-positive carcinomas but in only 6 (46%) of 13 p53-negative tumors (P = 0.01), In papillary serous carcinomas, MDM2 was detected in 9 (43%) of 21 p53-positive ca rcinomas but in none of the 4 p53-negative tumors (P value not signifi cant). These finding suggest that although high rates of p53 protein o verexpression are most frequently associated with p53 gene mutation in uterine papillary serous carcinoma, p53 protein overexpression in end ometrioid carcinoma is frequently associated with MDM2 overexpression. The selective correlation of MDM2 expression with p53 expression in e ndometrioid carcinomas but not in papillary serous carcinomas suggests an active role for MDM2 in binding and inactivating p53 in endometrio id carcinomas, leading to its overaccumulation and potentially impedin g repair to damaged DNA. Additional study as to the cause of increased MDM2 expression in endometrial carcinoma, e.g., gene amplification, e nhanced translation, or rearrangement, is indicated.