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Morphologic and Molecular Characteristics of Mixed Epithelial Ovarian Cancers.

混合型上皮性卵巢癌的形态学及分子特征

Mackenzie R,Talhouk A,Eshragh S,Lau S,Cheung D,Chow C,Le N,Cook LS,Wilkinson N,McDermott J,Singh N,Kommoss F,Pfisterer J,Huntsman DG,Köbel M,Kommoss S,Gilks CB,Anglesio MS

Abstract

Epithelial ovarian cancer (EOC) consists of 5 major histotypes: high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC), and low-grade serous carcinoma (LGSC). Each can have a broad spectrum of morphologic appearances, and 1 histotype can closely mimic histopathologic features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present on the basis of routine histopathologic assessment, histotype carcinoma diagnoses (3% to 11%); however, recent immunohistochemical (IHC) studies identifying histotype-specific markers and allowing more refined histotype diagnoses suggest a much lower incidence. We reviewed hematoxylin and eosin-stained slides from 871 cases of EOC and found the frequency of mixed carcinomas to be 1.7% when modern diagnostic criteria are applied. Through international collaboration, we established a cohort totaling 22 mixed EOCs, consisting of 9 EC/CCC, 4 EC/LGSC, 3 HGSC/CCC, 2 CCC/MC, and 4 other combinations. We interrogated the molecular differences between the different components of each case using IHC, gene expression, and hotspot sequencing analyses. IHC data alone suggested that 9 of the 22 cases were not mixed tumors, as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphologic mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. On the basis of these results, true mixed carcinomas with both morphologic and molecular support for the presence of >1 histotype within a given tumor represent <1% of EOCs.

摘要

上皮性卵巢癌(EOC)主要包含5种亚型:高级别浆液性癌(HGSC)、子宫内膜样癌(EC)、透明细胞癌(CCC)、粘液性癌(MC)及低级别浆液性癌(LGSC)。每种亚型都有非常宽泛的形态学表现,且不同亚型间的组织病理学特点可能会非常相似。既往基于常规的组织病理学评估,混合型癌(包括两种或两种以上亚型)出现的频率相对较高,达到3%-11%;但是最近由于鉴别不同亚型的特异性免疫组化(IHC)标记物的应用,研究表明混合性癌的发生率相对较低。作者评估了871例经苏木素和伊红染色的EOC切片,发现根据目前的诊断标准,混合型癌的发生率为1.7%。通过国际合作,作者建立了共计22例混合性EOCs的标本库,包含9例EC/CCC,4例EC/LGSC,3例 HGSC/CCC,2 例CCC/MC,及4例其它癌的不同组合。通过采用IHC、基因表达及热点测序分析来研究每例间不同组分之间的分子差异。IHC数据单一的显示22例中有9例不是混合性肿瘤,因为它们具有一致的免疫表型,这些病例极有可能代表一种单一类型肿瘤内部的形态学模拟及变异。综合分子数据,进一步降低了混合型癌的发生率。基于以上研究结果,对于肿瘤中>1种组织学类型、形态学和分子学上属于真正混合型的癌,在EOCs中所占比例<1%。



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