Synchronous Endometrial and Ovarian Carcinomas: Pathologic and Molecular Analysis Highlights the Monoclonal Origin of the Lesions.

IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY
Angela Guerriero, Margherita Moro, Valentina Angerilli, Giada Munari, Luisa Santoro, Lara Alessandrini, Lara Favero, Giulia Tasca, Matteo Fassan, Angelo Paolo Dei Tos
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Abstract

The diagnosis of synchronous carcinomas, involving both the endometrium and ovaries, is not a rare finding in gynecologic pathology and represents a challenge with implications on tumor staging and therapeutic decision-making. A mono-institutional series of 11 metastatic and 6 paired synchronous endometrial and ovarian carcinomas were reviewed by 2 expert pathologists based on previously published histopathologic criteria. The series was investigated for DNA mismatch repair proteins, p53, and POLE status and was subject to DNA-based next-generation sequencing targeting 67 cancer-related genes. Out of 17 pairs, 16 featured the same histotype (10 endometrioid, 4 serous high-grade, and 2 clear cells). By using WHO 2020 criteria, 11 couples of tumors were confirmed as metastatic and 6 couples were confirmed as independent. Based on next-generation sequencing analysis, 16 of 17 cases (11 metastatic and 5 independent) of our series showed evidence of a clonal relationship between endometrial and ovarian carcinomas. In metastatic cases, the adverse outcome was associated with nonendometrioid/high-grade endometrioid histotype and with the p53-abnormal molecular subtype. Four cases originally fulfilling clinicopathological criteria of independent endometrial and ovarian carcinomas were clonally related, low-grade endometrioid histotype and POLE -mut, mismatch repair deficient, and no specific molecular profile molecular subtypes; no adverse event was recorded in this group. In summary, the molecular characterization of synchronous gynecologic carcinomas confirms their clonal origin in most cases. However, the results of our study point out that the clinical behavior of these tumors seems to be determined by the presence of high-risk WHO 2020 histologic criteria and molecular features (i.e. p53-abnormal), rather than the monoclonal origin.

子宫内膜和卵巢同步癌:病理学和分子分析强调病变的单克隆起源。
同时涉及子宫内膜和卵巢的同步癌的诊断在妇科病理学中并不罕见,对肿瘤分期和治疗决策具有挑战性。2名专家病理学家根据先前发表的组织病理学标准,对11例转移性子宫内膜癌和6例同期子宫内膜癌及卵巢癌的单机构系列进行了审查。该系列研究了DNA错配修复蛋白、p53和POLE状态,并对67个癌症相关基因进行了基于DNA的下一代测序。在17对中,16对具有相同的组织类型(10个子宫内膜样,4个浆液性高级别,2个透明细胞)。根据世界卫生组织2020年标准,11对肿瘤被确认为转移性,6对被确认为独立性。基于下一代测序分析,我们系列的17例病例中有16例(11例转移,5例独立)显示出子宫内膜癌和卵巢癌之间存在克隆关系的证据。在转移病例中,不良结果与非子宫内膜样/高级子宫内膜样组织类型和p53异常分子亚型有关。4例最初符合独立子宫内膜癌和卵巢癌临床病理标准的病例为克隆相关、低度子宫内膜样组织型和POLE-mut、错配修复缺陷和无特定分子谱分子亚型;本组无不良事件记录。总之,同步性妇科癌的分子特征在大多数情况下证实了其克隆起源。然而,我们的研究结果指出,这些肿瘤的临床行为似乎是由世界卫生组织2020年高风险组织学标准和分子特征(即p53-异常)的存在决定的,而不是由单克隆来源决定的。
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来源期刊
CiteScore
3.90
自引率
12.50%
发文量
154
审稿时长
6-12 weeks
期刊介绍: International Journal of Gynecological Pathology is the official journal of the International Society of Gynecological Pathologists (ISGyP), and provides complete and timely coverage of advances in the understanding and management of gynecological disease. Emphasis is placed on investigations in the field of anatomic pathology. Articles devoted to experimental or animal pathology clearly relevant to an understanding of human disease are published, as are pathological and clinicopathological studies and individual case reports that offer new insights.
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