Mutation and expression of the TP53 gene in early stage epithelial ovarian carcinoma
Mutation and expression of the TP53 gene in early stage epithelial ovarian carcinoma
复制标题
DOI：
10.1016/j.ygyno.2004.01.043
复制
发表时间：
2004-05-01
影响因子：
4.7
通讯作者：
Boyd, J
中科院分区：
文献类型：
--
作者：
Leitao, MM;Soslow, RA;Boyd, J
目标。上皮性卵巢癌的早期自然历史仍然知之甚少。TP53基因突变在晚期（III-IV）卵巢癌中很常见，但在早期（I-II）肿瘤中描述较少。本研究旨在全面分析早期卵巢癌中TP53突变及p53表达状况。对73例不同组织学类型的肿瘤（I期46例，II期27例）进行了TP53全编码区和外显子-内含子连接的直接序列分析，并对p53的表达进行了免疫组化评价。总体而言，73例中有24例（34%）发现了突变。然而，观察到不同组织学类型的突变分布有显著差异；21例浆液性癌中有14例（67%）存在TP53突变，52例非浆液性癌中有II例（21%）存在TP53突变（P = 0.0002）。突变在I期和II期浆液组织学肿瘤中同样常见。关于TP53突变与p53免疫阳性之间的相关性，敏感性（58%）、特异性（71%）、阳性预测值（64%）和阴性预测值（83%）不足以证明p53表达作为替代或突变筛查的合理性。这些数据表明，TF53突变在浆液组织学的早期卵巢癌中很常见，其突变频率与晚期肿瘤的突变频率相当，因此可能发生在卵巢癌最常见的组织学变异进展的早期。(C) 2004爱思唯尔公司版权所有。
Objective. The early natural history of epithelial ovarian carcinoma remains poorly understood. Mutation of the TP53 gene is common in advanced-stage (III-IV) ovarian cancers, but less well described in early stage (I-II) tumors. The purpose of this study was to perform a comprehensive analysis of TP53 mutation and p53 expression status in early stage ovarian carcinomas.Methods. Seventy-three cases of various histologic types, including 46 stage I and 27 stage II tumors, were subjected to direct sequence analysis of the entire TP53 coding region and exon-intron junctions as well as immunohistochemical assessment of p53 expression.Results. Overall, mutations were identifi--d in 24 of 73 (34%) cases. However, a significant difference in the distribution of mutations among histologic types was observed; TP53 mutations were present in 14 of 21 (67%) serous cancers and II of 52 (21%) non-serous cancers (P = 0.0002). Mutations were equally common between stage I and stage II tumors of serous histology. With respect to the correlation between TP53 mutation and p53 immunopositivity, the sensitivity (58%), specificity (71%), positive predictive value (64%), and negative predictive value (83%) were not sufficiently robust to justify use of p53 expression as a surrogate or screen for mutation.Conclusions. These data indicate that TF53 mutation is common in early stage ovarian carcinomas of serous histology, with a mutation frequency comparable to that reported for advanced-stage tumors, and is therefore likely to occur early in the progression of the most common histologic variant of ovarian carcinoma. (C) 2004 Elsevier Inc. All rights reserved.