HER1-HER4 expression and co-expression in advanced urothelial carcinoma
In brief
All four HER receptors were expressed in 61% of advanced urothelial tumors
In this exploratory tumor analysis, 61% of tumors expressed all four HER receptors, and 96% expressed at least two, suggesting targets for antibody-drug conjugate research beyond HER2. HER1, HER3 and HER4 expression tracked with chemotherapy response, but none of the receptors was linked to overall survival; whether these patterns can guide treatment remains unknown.
- Journal
- ESMO open (Q1)
- Published
- 5 August 2026
- Study design
- Phase 2 randomized trial (exploratory)
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- S Coca Membribes, D M Berney, L Beltran, E Nally, F Jackson-Spence, B Szabados, et al.
- PMID
- 42785914
- DOI
- 10.1016/j.esmoop.2026.108317
Why clinicians should know about it
- Picked for Urology (paper of the day, 26 September 2026): HER1‑HER4 expression in advanced UC
Abstract
BACKGROUND: The human epidermal growth factor receptor (HER) family is under evaluation as a therapeutic target in urothelial cancer (UC); the significance of expression patterns beyond those of HER2 is unclear. PATIENTS AND METHODS: Tumour samples from a prospective randomised phase II-III trial (NCT00949455) were analysed by immunohistochemistry (IHC) and RNA profiling. Associations with molecular subtype, chemotherapy response, and overall survival (OS) were explored. The analyses were exploratory, and P values < 0.05 were considered relevant. RESULTS: A total of 446 tumours were tested for HER1/HER2, 77 for HER3, and 79 for HER4 expression. HER1-HER4 were positive (IHC 1-3+) in 89%, 80%, 77%, and 75% of tumours, respectively, with high expression (IHC 3+) in 34%, 12%, 26%, and 29%. Co-expression of all four receptors occurred in 61% of tumours, with concurrent high expression in 9%. Of the tumours, 96% expressed ≥2 receptors. Luminal tumours (n = 109) showed enriched HER2 expression (93% compared with 67%, P < 0.001), and basal tumours (n = 61) showed higher enriched HER3 expression (95% compared with 77%, P = 0.02). HER1 positivity correlated with better chemotherapy responses (P = 0.02) and HER3/HER4 positivity with poorer responses (P = 0.02 and P = 0.03, respectively). No differences in OS were observed. CONCLUSIONS: HER1-HER4 are broadly and concurrently expressed in advanced UC, supporting antibody-drug conjugate development beyond HER2. Receptor expression did not correlate with OS.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.