Hashem Sherin, Zare Somaye Y, Fadare Oluwole
Int J Gynecol Pathol. 2024 Jan 1;43(1):4-14. doi: 10.1097/PGP.0000000000000943. Epub 2023 Jun 9.
HER2 status is now routinely assessed in endometrial serous carcinoma (ESC) due to the reported predictive value of HER2 protein overexpression and/or gene amplification. Herein the authors compare 2 proposed testing and interpretation guidelines for HER2 in ESC. Forty-three consecutive cases of ESC that had been dually tested by both HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were interpreted using 2 sets of guidelines. Guideline set 1 (GS1) is the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines for breast cancer. Guideline set 2 (GS2) is a recent proposal that is a slight modification of the enrollment criteria for the clinical trial (NCT01367002) that demonstrated a survival benefit for anti-HER2 therapy in ESC. By IHC, GS1 and GS2, respectively classified 39.5% (17/43) and 28% (12/43) of ESC as HER2-negative, 37.2% (16/43) and 53.4% (23/43) as HER2 equivocal, and 23.2% (10/43) and 18.6% (8/43) as HER2-positive ( P > 0.05 for all). IHC and FISH were highly concordant at the extremes using either set of guidelines, as no cases were found to be IHC3+/FISH-negative or IHC 0-1+/FISH-positive. GS1 and GS2 were comparable regarding the proportion of IHC equivocal cases that were HER2 amplified by FISH (19% vs 23% respectively; [ P = 0.71]). GS1 and GS2 displayed 98% (42/43) concordance regarding the final (IHC and/or FISH-based) classification of tumors as being HER2-positive or negative, and the same 13 cases were ultimately classified as HER2 amplified using either GS1 or GS2. One "discordant" case was classified as HER2-positive using GS2 but HER2-negative using GS1 (HER2 IHC score 2+ using both guidelines, HER2:CEP17 signal ratio of 3, HER2 signal number of 3.4). Six (14%) of the 43 cases (FISH Groups: 2, 3, and 4) would require IHC results to interpret the FISH findings using GS1. Because GS1 requires that the HER2 IHC staining be observed within a homogeneous and contiguous invasive cell population, and this is not a requirement in GS2, GS2 may be better suited for ESC given its frequently heterogeneous staining pattern. Additional studies may be required on the optimal interpretation of problematic dual-probe FISH scenarios in GS2 and the necessity for IHC correlation in such scenarios. Using either set of guidelines, our findings support a reflex testing strategy of restricting FISH testing to cases that are IHC equivocal.
由于有报道称HER2蛋白过表达和/或基因扩增具有预测价值，目前在子宫内膜浆液性癌（ESC）中常规评估HER2状态。在此，作者比较了ESC中HER2检测和解读的2种提议指南。对43例连续的ESC病例同时进行HER2免疫组织化学（IHC）和荧光原位杂交（FISH）检测，并使用2套指南进行解读。指南集1（GS1）是2018年美国临床肿瘤学会/美国病理学家学会乳腺癌指南。指南集2（GS2）是最近的一项提议，是对临床试验（NCT01367002）入组标准的轻微修改，该试验证明抗HER2治疗对ESC有生存获益。通过IHC，GS1和GS2分别将39.5%（17/43）和28%（12/43）的ESC分类为HER2阴性，37.2%（16/43）和53.4%（23/43）为HER2不确定，23.2%（10/43）和18.6%（8/43）为HER2阳性（所有比较P>0.05）。使用任何一套指南，在极端情况下IHC和FISH高度一致，因为未发现病例为IHC3+/FISH阴性或IHC 0-1+/FISH阳性。在FISH检测为HER2扩增的IHC不确定病例比例方面，GS1和GS2相当（分别为19%和23%；[P=0.71]）。在肿瘤最终（基于IHC和/或FISH）分类为HER2阳性或阴性方面，GS1和GS2显示98%（42/43）的一致性，使用GS1或GS2最终有相同的13例病例被分类为HER2扩增。1例“不一致”病例使用GS2分类为HER2阳性，但使用GS1分类为HER2阴性（两套指南的HER2 IHC评分均为2+，HER2:CEP17信号比值为3，HER2信号数为3.4）。43例病例中的6例（14%）（FISH组：2、3和4）使用GS1时需要IHC结果来解读FISH结果。因为GS1要求在均匀且连续的浸润性细胞群体中观察HER2 IHC染色，而GS2没有这一要求，鉴于ESC的染色模式通常异质性，GS2可能更适合ESC。可能需要对GS2中有问题的双探针FISH情况的最佳解读以及此类情况下IHC相关性的必要性进行进一步研究。使用任何一套指南，我们的研究结果支持一种将FISH检测限制在IHC不确定病例的反射性检测策略。
