卵巢癌和腹膜低级别浆液性癌的分子替代亚型

IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY International Journal of Gynecological Pathology Pub Date : 2024-11-01 Epub Date: 2024-06-10 DOI:10.1097/PGP.0000000000001043
Annalyn Da-Anoy, Eun Young Kang, Cheng Han Lee, Dane Cheasley, Marta Llaurado Fernandez, Mark S Carey, Anna Cameron, Martin Köbel
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引用次数: 0

摘要

低级别浆液性癌(LGSC)是一种不常见的卵巢癌组织类型,约占病例的3%。有证据表明,腹膜低级别浆液性癌(pLGSC)的生存期长于卵巢低级别浆液性癌(oLGSC)。LGSC的关键分子改变已经确定,包括CDKN2A和PR表达缺失、MAPK通路改变和USP9X表达缺失。我们假设,可以通过一些类似于子宫内膜样癌的替代检测,根据单个改变的预后关联强度,使用分层决策树将 LGSC 亚分类为临床适用的分子亚型。我们的研究包括 71 例 LGSCs。对 CDKN2A、ER、PR、NF1 和 USP9X 进行了免疫组化,并对 KRAS、NRAS 和 BRAF 进行了测序。我们的数据显示了关键分子改变的共同发生,尽管有提示性趋势,但分子亚型的分层并不能根据患者的生存情况对其进行明显的分层。我们证实,确诊为 pLGSC 的患者比高期 oLGSC 患者的生存期更长,同时发现一个有趣的现象,即 CDKN2A 和 PR 正常与 pLGSC 患者的良好生存期相关。因此,CDKN2A和PR状态可能有助于对不确定的种植体进行分类,在不确定的种植体中,异常结果更倾向于pLGSC而非非浸润性种植体。分子亚型应在更大的队列中进一步评估其预后和潜在的预测价值。
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Molecular Surrogate Subtypes of Ovarian and Peritoneal Low-grade Serous Carcinoma.

Low-grade serous carcinoma (LGSC) is an uncommon histotype of ovarian carcinoma, accounting for ~3% of cases. There is evidence that survival of peritoneal LGSC (pLGSC) is longer than that of ovarian LGSC (oLGSC). Key molecular alterations of LGSC have been established, including loss of CDKN2A and PR expression, MAPK pathway alterations, and loss of USP9X expression. We hypothesized that LGSC could be subclassified into clinically applicable molecular subtypes by a few surrogate tests similar to endometrioid carcinomas using a hierarchical decision tree based on the strength of the prognostic associations of the individual alterations. Our study included 71 LGSCs. Immunohistochemistry for CDKN2A, ER, PR, NF1, and USP9X and sequencing for KRAS , NRAS , and BRAF were performed. Our data showed the co-occurrence of key molecular alterations, and despite suggestive trends, hierarchical molecular subtyping did not provide significantly different stratification of patients according to survival in this cohort. We confirmed that patients diagnosed with pLGSC have a longer survival than high-stage oLGSC, with the intriguing observation that normal CDKN2A and PR status were associated with excellent survival in pLGSC. Therefore, CDKN2A and PR status might aid in the classification of indeterminate implants, where abnormal findings favor pLGSC over noninvasive implants. Molecular subtypes should be further evaluated in larger cohorts for their prognostic and potentially predictive value.

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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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