MDM2 and p53 protein expression in the histologic subtypes of endometrial carcinoma.
The frequency of p53 protein overexpression differs among the histologic subtypes of endometrial carcinoma, from 21 to 48% in endometrioid carcinoma but from 80 to 86% in papillary serous carcinoma. Although p53 gene mutation can closely correlate with p53 protein overexpression in papillary serous carcinomas, high expression of p53 protein may also occur without detectable gene mutation in endometrioid carcinomas. Because MDM2 protein can bind mutant and wild-type p53 protein, we examined MDM2 and p53 protein expression in 27 endometrioid carcinomas and compared their expression patterns with those of 25 uterine papillary serous carcinomas. We detected p53 protein in 14 (52%) of the 27 endometrioid carcinomas but in 21 (84%) of the 25 papillary serous tumors (P = 0.02). MDM2 expression was more commonly detected in the endometrioid carcinomas. Nineteen (70%) of the 27 cases showed expression compared with 9 (36%) of the 25 papillary serous carcinomas (P = 0.03). p53 Expression correlated closely with MDM2 expression in endometrioid carcinomas but not in the papillary serous carcinomas. In endometrioid carcinomas, 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 carcinomas but in none of the 4 p53-negative tumors (P value not significant). These findings suggest that although high rates of p53 protein overexpression are most frequently associated with p53 gene mutation in uterine papillary serous carcinoma, p53 protein overexpression in endometrioid carcinoma is frequently associated with MDM2 overexpression. The selective correlation of MDM2 expression with p53 expression in endometrioid carcinomas but not in papillary serous carcinomas suggests an active role for MDM2 in binding and inactivating p53 in endometrioid carcinomas, leading to its overaccumulation and potentially impeding repair to damaged DNA. Additional study as to the cause of increased MDM2 expression in endometrial carcinoma, e.g., gene amplification, enhanced translation, or rearrangement, is indicated.
Ambros
R A
RA
Department of Pathology, Albany Medical College, New York 12208, USA.
Sheehan
C E
CE
Kallakury
B V
BV
Ross
J S
JS
Malfetano
J
J
Paunovich
E
E
Figge
J
J
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D018283:Cystadenocarcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2