Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mod Pathol. 2021 Jun;34(6):1194-1202. doi: 10.1038/s41379-021-00746-5. Epub 2021 Feb 3.
Targeted anti-human epidermal growth factor receptor 2 (HER2) therapy has recently been proven to improve progression-free and overall survival of patients with advanced stage or recurrent endometrial serous carcinoma. To date, no specific pathology HER2 testing or scoring guidelines exist for endometrial cancer. However, based on evidence from the recent successful clinical trial and comprehensive pre-trial pathologic studies, a new set of HER2 scoring criteria have been proposed for endometrial serous carcinoma-distinct from the existing breast and gastric cancer-specific criteria. We present the first study assessing interobserver agreement of HER2 scores using the proposed serous endometrial cancer-specific scoring system. A digitally scanned set of 40 HER2-immunostained slides of endometrial serous carcinoma were sent to seven gynecologic pathologists, who independently assigned HER2 scores for each slide following a brief tutorial. Follow-up fluorescent in situ hybridization (FISH) for HER2 gene amplification was performed on cases with interobserver disagreement when a 2+ HER2 score was assigned by at least one observer. Complete agreement of HER2 scores among all 7 observers was achieved on 15 cases, and all but one case had an agreement by at least 4 observers. The overall agreement was 72.3% (kappa 0.60), 77.5% (kappa 0.65), and 83.3% (kappa 0.65), using four (0 to 3+ ), three (0/1+ , 2+ , 3+ ), or two (0/1+ , 2/3+ ) HER2 scoring categories, respectively. Based on the combination of HER2 immunostaining scores and FISH, the interobserver disagreement may have potentially resulted in a clinically significant difference in HER2 status only in three tumors. We conclude, that the proposed serous endometrial cancer-specific HER2 scoring criteria are reproducible among gynecologic pathologists with moderate to substantial interobserver agreement rates comparable to those of previously reported in breast and gastric carcinomas. Our findings significantly strengthen the foundation for establishing endometrial cancer-specific HER2 scoring guidelines in the future.
针对人表皮生长因子受体 2（HER2）的靶向治疗最近已被证明可改善晚期或复发性子宫内膜浆液性癌患者的无进展生存期和总生存期。迄今为止，尚无针对子宫内膜癌的特定病理 HER2 检测或评分指南。然而，基于最近成功的临床试验和全面的术前病理研究的证据，已经提出了一套新的用于子宫内膜浆液性癌的 HER2 评分标准，与现有的乳腺癌和胃癌特异性标准不同。我们首次报告了使用新提出的针对浆液性子宫内膜癌的特异性评分系统评估 HER2 评分的观察者间一致性的研究。一组 40 例 HER2 免疫组化染色的子宫内膜浆液性癌数字扫描幻灯片被发送给 7 位妇科病理学家，他们在接受简短教程后独立为每张幻灯片分配 HER2 评分。当至少一位观察者分配 2+ HER2 评分时，对具有观察者间差异的病例进行后续荧光原位杂交（FISH）检测 HER2 基因扩增。在 15 例中，所有 7 位观察者的 HER2 评分完全一致，所有病例中至少有 4 位观察者的评分一致。当使用 4 个（0 至 3+）、3 个（0/1+、2+、3+）或 2 个（0/1+、2/3+）HER2 评分类别时，总体一致性分别为 72.3%（kappa 0.60）、77.5%（kappa 0.65）和 83.3%（kappa 0.65）。基于 HER2 免疫组化评分和 FISH 的组合，观察者间的差异可能仅导致 3 个肿瘤的 HER2 状态具有潜在的临床显著差异。我们得出结论，针对浆液性子宫内膜癌的新提出的 HER2 评分标准在妇科病理学家中具有可重复性，观察者间的一致性率中等至较高，与之前在乳腺癌和胃癌中报道的相似。我们的研究结果显著加强了未来在子宫内膜癌中建立 HER2 评分指南的基础。
