Hoang Lien N, McConechy Melissa K, Köbel Martin, Anglesio Michael, Senz Janine, Maassen Malden, Kommoss Stefan, Meng Bo, Postovit Lynne, Kelemen Linda E, Staebler Annette, Brucker Sara, Krämer Bernhard, McAlpine Jessica N, Gilks C Blake, Huntsman David G, Lee Cheng-Han
*Department of Pathology and Laboratory Medicine, and Genetic Pathology Evaluation Center, Vancouver General Hospital; †University of British Columbia, Vancouver; ‡Department of Pathology and Laboratory Medicine, Calgary Laboratory Services; §University of Calgary, Calgary, Canada; ∥Department of Gynecology and Obstetrics, Tübingen University, Tübingen, Germany; ¶Department of Laboratory Medicine and Pathology, Royal Alexandra Hospital; #University of Alberta; **Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada; ††Department of Public Health Sciences, Medical University of South Carolina; ‡‡Hollings Cancer Center, Charleston, SC; and §§Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, Canada.
Int J Gynecol Cancer. 2015 Sep;25(7):1187-93. doi: 10.1097/IGC.0000000000000492.
Polymerase epsilon (POLE) is a DNA polymerase with a proofreading (exonuclease) domain, responsible for the recognition and excision of mispaired bases, thereby allowing high-fidelity DNA replication to occur. The Cancer Genome Atlas research network recently identified an ultramutated group of endometrial carcinomas, characterized by mutations in POLE, and exceptionally high substitution mutation rates. These POLE mutated endometrial tumors were almost exclusively of the endometrioid histotype. The prevalence and patterns of POLE mutated tumors in endometrioid carcinomas of the ovary, however, have not been studied in detail.
In this study, we investigate the frequency of POLE exonuclease domain mutations in a series of 89 ovarian endometrioid carcinomas.
We found POLE mutations in 4 of 89 (4.5%) cases, occurring in 3 of 23 (13%) International Federation of Gynecology and Obstetrics (FIGO) grade 1, 1 of 43 (2%) FIGO grade 2, and 0 of 23 (0%) FIGO grade 3 tumors. All mutations were somatic missense point mutations, occurring at the commonly reported hotspots, P286R and V411L. All 3 POLE-mutated FIGO grade 1 tumors displayed prototypical histology, and the POLE-mutated FIGO grade 2 tumor displayed morphologic heterogeneity with focally high-grade features. All 4 patients with POLE-mutated tumors followed an uneventful clinical course with no disease recurrence; however, this finding was not statistically significant (P = 0.59).
The low rate of POLE mutations in ovarian endometrioid carcinoma and their predominance within the low FIGO grade tumors are in contrast to the findings in the endometrium.
聚合酶ε（POLE）是一种具有校对（核酸外切酶）结构域的DNA聚合酶，负责识别和切除错配碱基，从而实现高保真DNA复制。癌症基因组图谱研究网络最近鉴定出一组超突变的子宫内膜癌，其特征是POLE发生突变，且替换突变率异常高。这些POLE突变的子宫内膜肿瘤几乎均为子宫内膜样组织学类型。然而，卵巢子宫内膜样癌中POLE突变肿瘤的患病率和模式尚未得到详细研究。
在本研究中，我们调查了89例卵巢子宫内膜样癌中POLE核酸外切酶结构域突变的频率。
我们在89例病例中的4例（4.5%）发现了POLE突变，其中国际妇产科联盟（FIGO）1级的23例中有3例（13%）、FIGO 2级的43例中有1例（2%）、FIGO 3级的23例中无1例（0%）发生突变。所有突变均为体细胞错义点突变，发生在常见报道的热点区域P286R和V411L。所有3例POLE突变的FIGO 1级肿瘤均表现为典型组织学，POLE突变的FIGO 2级肿瘤表现为形态学异质性，具有局灶性高级别特征。4例POLE突变肿瘤患者的临床过程均顺利，无疾病复发；然而，这一发现无统计学意义（P = 0.59）。
卵巢子宫内膜样癌中POLE突变率较低，且主要发生在FIGO低级别肿瘤中，这与子宫内膜癌的研究结果形成对比。
