p53 和 BAF-250a（ARID1A）在子宫内膜透明细胞癌中的表达的临床病理意义。
The clinicopathologic significance of p53 and BAF-250a (ARID1A) expression in clear cell carcinoma of the endometrium.
机构信息
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
出版信息
Mod Pathol. 2013 Aug;26(8):1101-10. doi: 10.1038/modpathol.2013.35. Epub 2013 Mar 22.
TP53 mutation (and associated p53 protein overexpression) is probably a negative prognostic marker in endometrial cancers, but its relevance in the rarer histologic subtypes, including clear cell carcinomas, has not been delineated. Preclinical studies suggest functional interactions between p53 and the BAF250a protein, the product of a tumor suppressor gene ARID1A (adenine-thymine (AT)-rich interactive domain containing protein 1A) that is frequently mutated in ovarian clear cell carcinoma. In this study, we evaluated the significance of p53 and BAF250a expression, as assessed by immunohistochemistry, in a group of 50 endometrial clear cell carcinomas. Of 50 cases, 17 (34%) were p53+, and the remaining 33 cases had a p53 wild-type (p53-wt) immunophenotype. Of the 11 relapses/recurrences in the entire data set, 73% were in the p53+ group (P=0.008). On univariate analyses, the median overall survival for the p53-wt patients (83 months) was longer than the p53+ patients (63 months) (P=0.07), and the median progression-free survival for the p53-wt group (88 months) was significantly longer than the p53+ group (56 months) (P=0.01). On multivariate analyses, p53 expression was not associated with reduced overall or progression-free survival. In addition, p53 status was not significantly associated with pathologic stage or morphologic patterns. Of the 50 cases, 10 (20%) showed a complete loss of BAF250a expression. There was no significant correlation between p53 and BAF250a expression. The p53+/BAF250a-, p53+/BAF250a+, p53-wt/BAF250a+ and p53-wt/BAF250a- composite immunophenotypes were identified in 8%, 26%, 54% and 12% of cases, respectively, and neither loss of BAF250a expression nor composite p53/BAF250a expression patterns were associated with reduced overall or progression-free survival. In conclusion, a significant subset of CCC express p53, and these cases are apparently not definable by their morphologic features. P53 expression may be a negative prognostic factor in this histotype, and warrants additional studies. Loss of BAF250a expression has no prognostic significance in endometrial clear cell carcinomas.
TP53 突变（及其相关的 p53 蛋白过表达）可能是子宫内膜癌的一个负预后标志物，但在包括透明细胞癌在内的罕见组织学亚型中，其相关性尚未明确。临床前研究表明，p53 与 BAF250a 蛋白之间存在功能相互作用，BAF250a 蛋白是抑癌基因 ARID1A（富含腺嘌呤-胸腺嘧啶（AT）的相互作用域蛋白 1A）的产物，在卵巢透明细胞癌中经常发生突变。在这项研究中，我们评估了一组 50 例子宫内膜透明细胞癌中 p53 和 BAF250a 表达的意义，这些表达通过免疫组织化学进行评估。在 50 例病例中，17 例（34%）为 p53+，其余 33 例为 p53 野生型（p53-wt）免疫表型。在整个数据集的 11 例复发/复发中，73%发生在 p53+组（P=0.008）。在单因素分析中，p53-wt 患者的中位总生存期（83 个月）长于 p53+患者（63 个月）（P=0.07），p53-wt 组的中位无进展生存期（88 个月）明显长于 p53+组（56 个月）（P=0.01）。在多因素分析中，p53 表达与总生存期或无进展生存期的降低无关。此外，p53 状态与病理分期或形态模式无显著相关性。在 50 例病例中，有 10 例（20%）显示 BAF250a 表达完全缺失。p53 和 BAF250a 表达之间没有显著相关性。p53+/BAF250a-、p53+/BAF250a+、p53-wt/BAF250a+和 p53-wt/BAF250a-复合免疫表型分别在 8%、26%、54%和 12%的病例中发现，并且 BAF250a 表达缺失或复合 p53/BAF250a 表达模式均与总生存期或无进展生存期的降低无关。总之，透明细胞癌的一个重要亚组表达 p53，这些病例显然不能通过其形态特征来定义。p53 表达可能是这种组织类型的一个负预后因素，值得进一步研究。BAF250a 表达缺失在子宫内膜透明细胞癌中无预后意义。
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