Department of Pathology and Laboratory Medicine, Calgary Laboratory Services/Alberta Health Services and University of Calgary, Canada.
J Pathol. 2010 Oct;222(2):191-8. doi: 10.1002/path.2744.
Studies on the p53 expression and outcome for women with ovarian carcinoma have produced conflicting results. The observed heterogeneity may be due to the range of cut-offs used to define overexpression and the mix of histotypes of the study cohorts. We aimed to examine the association between p53 expression and biological properties of tumours as well as outcome in 502 pelvic high-grade serous carcinomas (HGSCs) derived from two population-based cohorts from British Columbia representing cases with or without residual tumour after initial surgery, respectively, and one clinical trial cohort from Germany (AGO-OVAR-3). p53 expression was assessed on tissue microarrays by immunohistochemistry using the DO-7 antibody. p53 expression was scored in three tiers as complete loss of expression, focal expression or overexpression (defined as more than 50% positive tumour cell nuclei) and correlated with survival using multivariate Cox regression models. p53 was completely absent in 30.3%, focally expressed in 12.0%, and overexpressed in 57.7% of HGSCs, which was an inverse pattern compared to clear cell and endometrioid types of ovarian carcinomas, where 76% and 69% of cases showed focal expression, respectively (p < 0.001, chi square test). Pelvic HGSCs show either complete absence of p53 expression or p53 overexpression in 88% of cases; thus, aberrant p53 expression is a ubiquitous feature of HGSCs. HGSCs with p53 overexpression were associated with a reduced risk of recurrence compared to cases with complete absence of p53 in the British Columbia cohort with residual tumour (HR = 0.71, 95% CI 0.51-0.99) and for a combination of all three cohorts (HR = 0.70, 95% CI 0.55-0.89) in multivariate analysis including age, stage, residual tumour, and stratification by cohort. The association of complete absence of p53 expression with unfavourable outcome suggests functional differences of TP53 mutations underlying overexpression, compared to those underlying complete absence of expression.
对卵巢癌患者 p53 表达和结果的研究产生了相互矛盾的结果。观察到的异质性可能是由于用于定义过度表达的截止值范围以及研究队列的组织类型混合所致。我们旨在检查 502 例来自不列颠哥伦比亚省的基于人群队列的盆腔高级别浆液性癌（HGSC）中 p53 表达与肿瘤生物学特性以及结局之间的关联，这些队列分别代表初始手术后有无残留肿瘤的病例，以及来自德国的一项临床试验队列（AGO-OVAR-3）。使用 DO-7 抗体通过免疫组织化学在组织微阵列上评估 p53 表达。p53 表达评分分为三个层次，完全缺失表达、局灶性表达或过度表达（定义为超过 50%的肿瘤细胞核阳性），并使用多变量 Cox 回归模型与生存相关联。在 30.3%的 HGSC 中完全缺失 p53，在 12.0%的 HGSC 中局灶性表达，在 57.7%的 HGSC 中过度表达，与透明细胞癌和子宫内膜样卵巢癌的表达模式相反，其中分别有 76%和 69%的病例显示局灶性表达（p<0.001，卡方检验）。盆腔 HGSC 中 88%的病例要么完全缺失 p53 表达，要么 p53 过度表达；因此，异常的 p53 表达是 HGSC 的普遍特征。与不列颠哥伦比亚省残留肿瘤队列中完全缺失 p53 的病例相比，p53 过度表达的 HGSC 复发风险降低（HR=0.71，95%CI 0.51-0.99），在包括年龄、分期、残留肿瘤和按队列分层的多变量分析中，所有三个队列的组合（HR=0.70，95%CI 0.55-0.89）。完全缺失 p53 表达与不良结局相关，这表明与完全缺失表达相比，TP53 突变导致过度表达的功能差异。
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