Morphologic and Molecular Characteristics of Mixed Epithelial Ovarian Cancers.
Morphologic and Molecular Characteristics of Mixed Epithelial Ovarian Cancers.
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DOI：
10.1097/pas.0000000000000476
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发表时间：
2015-11
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通讯作者：
Anglesio MS
中科院分区：
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作者：
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
上皮性卵巢癌包括5种主要组织型：高级别浆液性癌（HGSC）、类浆液性癌（EC）、透明细胞癌（CCC）、粘液性癌（MC）和低级别浆液性癌（LGSC）。每种组织型都有广泛的形态学表现，一种组织型可以很好地模拟另一种组织型的组织病理学特征。从历史上看，混合型（根据常规组织病理学评估，存在2种或2种以上不同的组织型）的频率相对较高，组织型癌诊断（3-11%），但最近的免疫组织化学研究确定了组织型特异性标记物，并允许更精确的组织型诊断，表明发生率要低得多。我们回顾了871例上皮性卵巢癌的苏木精和伊红染色切片，发现当应用现代诊断标准时，混合癌的频率为1.7%。通过国际合作，我们建立了一个共22例混合性上皮性卵巢癌的队列，包括9例EC/CCC，4例EC/LGSC，3例HGSC/CCC，2例CCC/MC和4例其他组合。我们使用免疫组织化学、基因表达和热点测序分析来询问每个病例不同组分之间的分子差异。仅免疫组化数据表明，22例中有9例不是混合瘤，因为它们呈现出一致的免疫表型，这些病例最可能代表单一组织型肿瘤内的形态学模仿和变异。分子数据的综合进一步降低了混合癌的发生率。基于这些结果，真正的混合癌与形态学和分子支持的存在下，一个给定的肿瘤内的一个以上的组织型代表不到1%的上皮性卵巢癌。
Epithelial ovarian cancer consists of 5 major histotypes: high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC) and low-grade serous (LGSC). Each can have a broad spectrum of morphological appearances, and one histotype can closely mimic histopathological features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present based on routine histopathological assessment, histotype carcinoma diagnoses (3–11%), however recent immunohistochemical studies identifying histotype specific markers and allowing more refined histotype diagnoses suggests a much lower incidence. We reviewed hematoxylin and eosin stained slides from 871 cases of epithelial ovarian cancer 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 epithelial ovarian cancers, 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 immunohistochemistry, gene expression and hotspot sequencing analyses. Immunohistochemical data alone suggested 9 of the 22 cases were not mixed tumors as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphological mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. Based on these results, true mixed carcinomas with both morphological and molecular support for the presence of more than one histotype within a given tumor represent less than 1% of epithelial ovarian cancers.