HER-2 Amplification in Uterine Serous Carcinoma and Serous Endometrial Intraepithelial Carcinoma

xloma.fota13 shared this article with you from Inoreader HER-2 Amplification in Uterine Serous Carcinoma and Serous Endometrial Intraepithelial Carcinoma Via The American Journal of Surgical Pathology - Published Ahead-of-Print Human epidermal growth factor receptor 2 (HER-2) targeted therapy shows promising results in HER-2-positive uterine serous carcinoma (USC). HER-2 scoring criteria for USC and its associated noninvasive lesion, serous endometrial intraepithelial carcinoma (SEIC), are not well-established. Here, we compare the breast and gastric (GI) HER-2 immunohistochemistry (IHC) scoring criteria for HER-2 with HER-2/neu fluorescence in situ hybridization (FISH) in 68 tumors (17 USC with SEIC, 30 USC, 18 SEIC, 3 metastatic USC). The majority (97%) of lesions displayed intratumoral HER-2 IHC heterogeneity. Breast or GI IHC scoring criteria were performed equivalently. The breast and GI IHC criteria classified 51% and 47% USC as HER-2 negative (IHC 0/1+), 40% and 45% as equivocal (IHC 2+), and 9% each as HER-2 positive (IHC 3+). A quarter of USC classified as HER-2 negative or positive with the breast (25%, n=7/28) or GI IHC criteria (23%, n=6/26) was discordant by FISH. Specifically, 13% to 14% of IHC 0/1+ USC were FISH amplified; 50% of IHC 3+ USC were FISH negative. The majority (77% to 83%) of SEIC were HER-2 IHC 0/1+, and no SEIC was HER-2 IHC 3+. A minority (4% to 7%) of IHC 0/1+ SEIC were FISH positive. Discordant HER-2 status was observed between half (47%,bn=7/15) of synchronous SEIC and USC. In conclusion, USC di splays HER-2 intratumoral heterogeneity, a high IHC/FISH discordance rate, and variation in HER-2 status between the SEIC and invasive components. Caution is required when evaluating HER-2 in small biopsies, which should be repeated on excisions. Both IHC and FISH should be performed on USC until clinical trials correlate HER-2 status with clinical response to HER-2-targeted therapy. N.B. and A.C.-M.: developed the study concept, generated the study's data, and prepared the manuscript. D.B. and R.Y.: performed FISH testing and generated this data. A.N.F.: helped develop the study concept and assisted in manuscript preparation and provided clinical context. M.S.: assisted in data analysis and manuscript preparation. E.J.T.: assisted in study design, manuscript preparation, and provided clinical context. Conflicts of Interest and Source of Funding: Support was provided to facilitate this research from Genentech (A.C.-M.) and the Dr Susan Burgert Research Endowment (A.N.F.). A.C.-M. receives grant funding from Bristol-Myers Squibb and is a paid consultant for Bristol-Meyers Squibb and Roche Diagnostics. The remaining authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Natalie Banet, MD, Department of Pathology and Laboratory Medicine, Women & Infants Hospital and the Warren Alpert Medical School of Brown University, 101 Dudley Street, Providence, RI 02905 (e-mail: nbanet@kentri.org). Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.