Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Mod Pathol. 2013 Dec;26(12):1605-12. doi: 10.1038/modpathol.2013.113. Epub 2013 Jun 14.
HER2 overexpression and/or amplification have been reported in endometrial serous carcinoma, suggesting that HER2 may be a promising therapeutic target. However, there is considerable variation in the reported rates of HER2 overexpression and amplification, likely--at least in part--resulting from variability in the testing methods, interpretation, and scoring criteria used. Unlike in breast and gastric cancer, currently there are no established guidelines for HER2 testing in endometrial carcinoma. A total of 108 endometrial carcinoma cases--85 pure serous carcinomas and 23 mixed endometrial carcinomas with serous component--were identified over a 4-year period. All H&E and HER2 immunohistochemical slides were reviewed and HER2 FISH results (available on 52 cases) were retrieved from pathology reports. HER2 immunohistochemical scores were assigned according to the FDA criteria and the current breast ASCO/CAP scoring criteria. Clinical information was retrieved from the patients' medical records. Thirty-eight cases (35%) showed HER2 overexpression and/or gene amplification, 20 of which (53%) had significant heterogeneity of protein expression by immunohistochemistry. Lack of apical membrane staining resulting in a lateral/basolateral staining pattern was observed in the majority of HER2-positive tumors. Five of the HER2-positive cases (13%) demonstrated discrepant immunohistochemical scores when using the FDA versus ASCO/CAP scoring system. The overall concordance rate between HER2 immunohistochemistry and FISH was 75% (39/52) when using the FDA criteria, compared with 81% (42/52) by the ASCO/CAP scoring system. In conclusion, in this largest comprehensive study, 35% of endometrial serous carcinoma harbors HER2 protein overexpression and/or gene amplification, over half of which demonstrate significant heterogeneity of protein expression. The current breast ASCO/CAP scoring criteria provide the highest concordance between immunohistochemistry and FISH. Assessment of HER2 immunohistochemistry on multiple tumor sections or sections with large tumor areas is recommended, due to the significant heterogeneity of HER2 protein expression.
HER2 过表达和/或扩增已在子宫内膜浆液性癌中报道，提示 HER2 可能是一个有前途的治疗靶点。然而，HER2 过表达和扩增的报道率存在相当大的差异，这可能至少部分是由于测试方法、解释和评分标准的可变性。与乳腺癌和胃癌不同，目前尚无子宫内膜癌 HER2 检测的既定指南。在 4 年期间，共确定了 108 例子宫内膜癌病例 - 85 例纯浆液性癌和 23 例伴有浆液性成分的混合性子宫内膜癌。所有 H&E 和 HER2 免疫组化切片均进行了复查，并从病理报告中检索了 HER2 FISH 结果（可用于 52 例）。HER2 免疫组化评分根据 FDA 标准和当前的乳腺癌 ASCO/CAP 评分标准进行分配。临床信息从患者的病历中检索。38 例（35%）显示 HER2 过表达和/或基因扩增，其中 20 例（53%）免疫组化显示蛋白表达存在显著异质性。大多数 HER2 阳性肿瘤中观察到缺乏顶膜染色导致侧向/基底外侧染色模式。在使用 FDA 与 ASCO/CAP 评分系统时，5 例 HER2 阳性病例（13%）的免疫组化评分存在差异。使用 FDA 标准时，HER2 免疫组化与 FISH 的总一致性率为 75%（39/52），而使用 ASCO/CAP 评分系统时为 81%（42/52）。总之，在这项最大的综合研究中，35%的子宫内膜浆液性癌存在 HER2 蛋白过表达和/或基因扩增，其中一半以上显示蛋白表达存在显著异质性。目前的乳腺癌 ASCO/CAP 评分标准在免疫组化和 FISH 之间提供了最高的一致性。由于 HER2 蛋白表达存在显著异质性，建议对多个肿瘤切片或肿瘤面积较大的切片进行 HER2 免疫组化评估。
