Chen Wenqian, Husain Arjumand, Nelson Gregg S, Rambau Peter F, Liu Shuhong, Lee Cheng-Han, Lee Sandra, Duggan Máire A, Köbel Martin
Department of Pathology and Laboratory Medicine (W.C., P.F.R., S.Liu., S.Lee., M.A.D., M.K.), University of Calgary Division of Gynecologic Oncology (G.S.N.), Tom Baker Cancer Centre, Calgary Department of Pathology and Laboratory Medicine (C.H.L.), University of Alberta Division of Pathology and Laboratory Medicine (A.H.), Chinook Regional Hospital, Lethbridge, AB, Canada.
Int J Gynecol Pathol. 2017 Mar;36(2):128-139. doi: 10.1097/PGP.0000000000000291.
Endometrial serous carcinoma (ESC) is an aggressive neoplasm mainly seen in older women. The objective of this study was to refine immunohistochemical (IHC) panels for the differential diagnoses against endometrial endometrioid grade 3 (EC3), endometrial clear cell, and ovarian high-grade serous carcinoma as well as exploring the prognostic role of selected IHC markers. Fifty-two ESC from a single institution were assessed for 20 IHC markers, including ARID1A, CCNE1, CDKN2A, ERBB2, ESR1, HNF1B, FBXW7, IGF2BP3, MLH1, MSH2, MSH6, NAPSA, PAX8, PGR, PMS2, PTEN, TFF3, TP53, VIM, and WT1. ERBB2 chromogenic in situ hybridization was evaluated on tissue microarrays. Statistical analysis was performed. All ESC showed aberrant TP53, normal mismatch repair protein, and retained ARID1A and PTEN expression. ESR1 expression was present in 80% of ESC. A combination of TP53, PTEN, and CDKN2A had a sensitivity of 93.6% [95% confidence interval (CI), 84%-98%] and specificity of 87.8% (95% CI, 75%-95%) for ESC versus EC3. A combination of NAPSA and ESR1 had a sensitivity of 97.9% (95% CI, 89%-99%) and specificity of 72.2% (95% CI, 46%-90%) for ESC versus clear cell carcinoma. Absence of WT1 alone had a sensitivity of 66.0% (95% CI, 51%-79%) and specificity of 98.0% (95% CI, 94%-99%) for ESC versus ovarian high-grade serous carcinoma. Among all 52 ESCs, ERBB2 amplification was present in 23%, FBXW7 expression was absent in 10%, and CCNE1 was overexpressed in 59%, however, none were associated with prognosis. Our data support the value of IHC marker panels for histotyping of high-grade endometrial carcinomas.
子宫内膜浆液性癌（ESC）是一种侵袭性肿瘤，主要见于老年女性。本研究的目的是完善免疫组织化学（IHC）检测组合，用于与子宫内膜样3级腺癌（EC3）、子宫内膜透明细胞癌和卵巢高级别浆液性癌进行鉴别诊断，并探索所选免疫组化标志物的预后作用。对来自单一机构的52例ESC进行了20种免疫组化标志物检测，包括ARID1A、CCNE1、CDKN2A、ERBB2、ESR1、HNF1B、FBXW7、IGF2BP3、MLH1、MSH2、MSH6、NAPSA、PAX8、PGR、PMS2、PTEN、TFF3、TP53、VIM和WT1。在组织芯片上评估ERBB2显色原位杂交。进行了统计分析。所有ESC均显示TP53异常、错配修复蛋白正常，并保留ARID1A和PTEN表达。80%的ESC存在ESR1表达。TP53、PTEN和CDKN2A联合检测对ESC与EC3的敏感性为93.6%[95%置信区间（CI），84%-98%]，特异性为87.8%（95%CI，75%-95%）。NAPSA和ESR1联合检测对ESC与透明细胞癌的敏感性为97.9%（95%CI，89%-99%），特异性为72.2%（95%CI，46%-90%）。单独WT1缺失对ESC与卵巢高级别浆液性癌的敏感性为66.0%（95%CI，51%-79%），特异性为98.0%（95%CI，94%-99%）。在所有52例ESC中，23%存在ERBB2扩增，10%无FBXW7表达，59%CCNE1过表达，然而，均与预后无关。我们的数据支持免疫组化标志物检测组合对高级别子宫内膜癌组织分型的价值。
