Journal Article

Immunohistochemical Analysis of HER2, EGFR, and Nectin-4 Expression in Upper Urinary Tract Urothelial Carcinoma

Mamoru, Hashimoto, Kazuhiro, Yoshimura, Norio, Nonomura, Tetsuya, Takao, Kazutoshi, Fujita, Shogo, Adomi, Hirotsugu, Uemura, Masahiro, Nozawa, Hiroaki, Fushimi, Takafumi, Minami, Eisuke, Tomiyama, Saizo, Fujimoto, Eri, Banno

2023

Overview

Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, often discovered at an advanced stage at diagnosis. Nectin-4 is expressed in a broad range of patients with UTUC and is associated with poor progression-free survival. The receptors of the erythroblastosis oncogene B (ErbB) family are potential therapeutic targets for urothelial carcinoma. Herein, we aimed to investigate the relationship of nectin-4 and ErbB family receptors, namely epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in patients with UTUC. Targeted therapies for these receptors could be used in sequence or in combination for increasing treatment efficiency. We performed immunohisto-chemical analysis for HER2, EGFR, and nectin-4 using tissue microarrays. A total of 98 UTUC patients were included in the study. We investigated the impact of EGFR and HER2 expression status on recurrence-free survival (RFS) and cancer-specific survival (CSS) of all patients. The percentages of patients positive for HER2, EGFR, and nectin-4 were 97%, 70%, and 65%, respectively. The co-expression rates of HER2-EGFR, HER2-nectin-4, and EGFR-nectin-4 were 69%, 64%, and 47%, respectively. The number of patients positive for all three receptors was 47%. Higher HER2 levels were significantly associated with worse CSS and RFS. Higher EGFR levels were associated with a worse CSS. HER2, EGFR, and nectin-4 were highly expressed in UTUC. Combination of HER2-, EGFR-, and nectin-4-targeted therapy may be an effective option for the treatment of patients with UTUC.

• Publisher: Anticancer Research USA Inc,International Institute of Anticancer Research
• Subject: Bladder cancer / Breast cancer / Cancer / Cancer therapies / Carcinoma, Transitional Cell / Carcinoma, Transitional Cell - genetics / Carcinoma, Transitional Cell - metabolism / Cell growth / Chemical analysis / Chemotherapy / Clinical trials / Epidermal growth factor / Epidermal growth factor receptors / ErbB protein / ErbB Receptors / ErbB Receptors - genetics / ErbB Receptors - metabolism / ErbB-2 protein / Growth factors / Humans / Ligands / Medical prognosis / Medical research / Metastasis / Nectin / Nectins / Nectins - genetics / Nectins - metabolism / Prognosis / Receptor, ErbB-2 / Receptor, ErbB-2 - genetics / Receptor, ErbB-2 - metabolism / Receptors / Retrospective Studies / Review boards / Survival / Survival analysis / Therapeutic targets / Ureteral Neoplasms / Ureteral Neoplasms - genetics / Ureteral Neoplasms - metabolism / Urinary Bladder Neoplasms / Urinary Bladder Neoplasms - genetics / Urinary Bladder Neoplasms - metabolism / Urinary Tract / Urinary Tract - pathology / Urogenital system / Urothelial carcinoma