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.
Anticancer research. 2023 Jan [Epub]
Mamoru Hashimoto, Kazutoshi Fujita, Eisuke Tomiyama, Saizo Fujimoto, Shogo Adomi, Eri Banno, Takafumi Minami, Tetsuya Takao, Masahiro Nozawa, Hiroaki Fushimi, Kazuhiro Yoshimura, Norio Nonomura, Hirotsugu Uemura
Department of Urology, Kindai University, Faculty of Medicine, Osakasayama, Japan., Department of Urology, Kindai University, Faculty of Medicine, Osakasayama, Japan; ., Department of Urology, Osaka University, Graduate School of Medicine, Suita, Japan., Department of Urology, Osaka General Medical Center, Osaka, Japan., Department of Pathology, Osaka General Medical Center, Osaka, Japan.