Head-to-Head Comparison of the Expression Differences of NECTIN-4, TROP-2, and HER2 in Urothelial Carcinoma and Its Histologic Variants

Yu Fan; Qinhan Li; Qi Shen; Zhifu Liu; Zhenan Zhang; Shuai Hu; Wei Yu; Zhisong He; Qun He; Qian Zhang

doi:10.3389/fonc.2022.858865

Head-to-Head Comparison of the Expression Differences of NECTIN-4, TROP-2, and HER2 in Urothelial Carcinoma and Its Histologic Variants

Front Oncol. 2022 Apr 19:12:858865. doi: 10.3389/fonc.2022.858865. eCollection 2022.

Authors

Yu Fan¹, Qinhan Li¹, Qi Shen¹, Zhifu Liu¹, Zhenan Zhang¹, Shuai Hu¹, Wei Yu¹, Zhisong He¹, Qun He¹, Qian Zhang¹

Affiliation

¹ Department of Urology, Peking University First Hospital, Institute of Urology, National Research Center for Genitourinary Oncology, Peking University, Beijing, China.

Abstract

Background: Antibody-drug conjugates (ADC), such as enfortumab vedotin (EV), sacituzumab govitecan (SG), and RC-48, have shown outstanding response rates to local advanced or metastatic urothelial carcinoma (UC). However, their corresponding target expression characteristics in UC and its histologic variants were unknown.

Methods: We detected the expression of NECTIN-4, TROP-2, and HER2, which are the corresponding targets of ADCs EV, SG, and RC-48 in muscle-invasive UC through immunohistochemistry.

Results: 161 consecutive samples from 2017 to 2021 of muscle-invasive UC and its histologic variants were obtained in Peking University First Hospital. Variant histology types included 72UC, 10 squamous carcinomas, 23 glandular carcinomas, 19 small cell carcinomas, 19 micropapillary variants, and 18 nested variants. NECTIN-4 expression was found to be 57/72 (79.2%), 10/10 (100%), 15/23 (65.2%), 4/19 (21.1%), 15/19 (78.9%), and 16/18 (88.9%) in conventional UC, squamous carcinoma, glandular carcinoma, small cell carcinoma, micropapillary, and nested variant, respectively, compared with 65/72 (90.3%), 8/10 (80.0%), 13/23 (56.5%), 3/19 (15.8%), 16/19 (84.2%), and 15/18 (83.3%) of TROP-2, and 26/72 (36.1%), 0, 5/23 (21.7%), 6/19 (31.6%), 5/19 (26.3%), and 7/18 (38.9%) of HER2.

Keywords: ADC; HER2; Trop-2; histologic variants; nectin-4; urothelial carcinoma.