Ambros R A, Sheehan C E, Kallakury B V, Ross J S, Malfetano J, Paunovich E, Figge J
Department of Pathology, Albany Medical College, New York 12208, USA.
Mod Pathol. 1996 Dec;9(12):1165-9.
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.
p53蛋白过表达的频率在子宫内膜癌的不同组织学亚型中有所差异，在子宫内膜样癌中为21%至48%，而在乳头状浆液性癌中为80%至86%。虽然p53基因突变在乳头状浆液性癌中可能与p53蛋白过表达密切相关，但在子宫内膜样癌中，p53蛋白高表达也可能在未检测到基因突变的情况下发生。由于MDM2蛋白可与突变型和野生型p53蛋白结合，我们检测了27例子宫内膜样癌中的MDM2和p53蛋白表达，并将其表达模式与25例子宫乳头状浆液性癌的表达模式进行比较。我们在27例子宫内膜样癌中的14例（52%）检测到p53蛋白，但在25例乳头状浆液性肿瘤中的21例（84%）检测到p53蛋白（P = 0.02）。MDM2表达在子宫内膜样癌中更常见。27例中的19例（70%）显示有表达，而25例乳头状浆液性癌中的9例（36%）有表达（P = 0.03）。在子宫内膜样癌中，p53表达与MDM2表达密切相关，但在乳头状浆液性癌中并非如此。在子宫内膜样癌中，14例p53阳性癌中的13例（93%）检测到MDM2，但13例p53阴性肿瘤中仅6例（46%）检测到MDM2（P = 0.01）。在乳头状浆液性癌中，21例p53阳性癌中的9例（43%）检测到MDM2，但4例p53阴性肿瘤中均未检测到MDM2（P值无统计学意义）。这些发现表明，虽然子宫乳头状浆液性癌中p53蛋白过表达率高最常与p53基因突变相关，但子宫内膜样癌中p53蛋白过表达常与MDM2过表达相关。MDM2表达与子宫内膜样癌中p53表达的选择性相关性，而不是与乳头状浆液性癌中p53表达的相关性，表明MDM2在子宫内膜样癌中对p53的结合和失活起积极作用，导致其过度积累，并可能阻碍对受损DNA的修复。有必要对子宫内膜癌中MDM2表达增加的原因进行进一步研究，例如基因扩增、翻译增强或重排。
