Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Mod Pathol. 2017 Dec;30(12):1748-1759. doi: 10.1038/modpathol.2017.81. Epub 2017 Aug 4.
The Cancer Genome Atlas classification divides endometrial carcinoma in biologically distinct groups, and testing for p53, mismatch repair proteins (MMR), and polymerase ɛ (POLE) exonuclease domain mutations has been shown to predict the molecular subgroup and clinical outcome. While abnormalities in these markers have been described in ovarian endometrioid carcinoma, their role in predicting its molecular profile and prognosis is still not fully explored. Patients with ovarian endometrioid carcinomas treated surgically in a 14-year period were selected. Only tumors with confirmation of endometrioid histology and negative WT1 and Napsin-A were included. POLE mutational analysis and immunohistochemistry for p53, MLH1, MSH2, MSH6, and PMS2 was performed in formalin-fixed, paraffin-embedded tissue. Following the molecular classifier proposed for endometrial carcinoma (Br J Cancer2015;113:299-310), cases were classified as POLE mutated, MMR abnormal, p53 abnormal, and p53 wild type. Clinicopathologic information was recorded, including patient outcome. In all, 72 cases were included, distributed as follows: 7 (10%) POLE mutated; 6 (8%) MMR abnormal; 17 (24%) p53 abnormal; and 42 (58%) p53 wild type. The molecular classification correlated with disease-free survival in multivariate analysis (P=0.003), independently of tumor grade and stage. Correlation with overall survival approached statistical significance (P=0.051). POLE-mutated and MMR-abnormal tumors had excellent survival, whereas p53-abnormal tumors had significantly higher rates of recurrence and death. Ovarian endometroid carcinoma can be classified in clinically meaningful subgroups by testing for molecular surrogates, akin to endometrial cancer. MMR and POLE alterations seem to identify a subset of ovarian endometrioid carcinomas with excellent outcome; conversely, abnormal p53 carries a worse prognosis. In the era of personalized medicine, the use of these markers in the routine evaluation of ovarian endometrioid tumors should be considered.
癌症基因组图谱分类将子宫内膜癌分为生物学上不同的组，并且已经证明检测 p53、错配修复蛋白（MMR）和聚合酶ɛ（POLE）外切酶结构域突变可以预测分子亚组和临床结果。虽然已经在卵巢子宫内膜样癌中描述了这些标志物的异常，但它们在预测其分子特征和预后中的作用尚未完全探索。选择了在 14 年内接受手术治疗的卵巢子宫内膜样癌患者。仅纳入肿瘤组织学证实为子宫内膜样、WT1 和 Napsin-A 均为阴性的患者。在福尔马林固定、石蜡包埋的组织中进行 POLE 突变分析和 p53、MLH1、MSH2、MSH6 和 PMS2 的免疫组织化学染色。根据子宫内膜癌（Br J Cancer 2015;113:299-310）提出的分子分类器，将病例分为 POLE 突变、MMR 异常、p53 异常和 p53 野生型。记录了临床病理信息，包括患者的结局。总共纳入 72 例患者，分布如下：7 例（10%）POLE 突变；6 例（8%）MMR 异常；17 例（24%）p53 异常；42 例（58%）p53 野生型。多变量分析显示，分子分类与无病生存率相关（P=0.003），与肿瘤分级和分期无关。与总生存率的相关性接近统计学意义（P=0.051）。POLE 突变和 MMR 异常的肿瘤生存良好，而 p53 异常的肿瘤复发和死亡的风险显著更高。卵巢子宫内膜样癌可以通过检测分子替代物分为具有临床意义的亚组，类似于子宫内膜癌。MMR 和 POLE 改变似乎可以识别出一组具有良好结局的卵巢子宫内膜样癌；相反，异常的 p53 预后较差。在个性化医疗时代，应考虑在卵巢子宫内膜样肿瘤的常规评估中使用这些标志物。
