Related Experiment Video
Updated: Sep 26, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
HER1-HER4 expression and co-expression in advanced urothelial carcinoma
S Coca Membribes1, D M Berney2, L Beltran3
1Barts Cancer Institute Biomedical Research Centre/Barts ECMC, Queen Mary University of London, London, UK.
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.
