Human epidermal growth factor receptor 2/neu expression in urothelial carcinomas

Abstract

Urothelial carcinomas of the bladder are more common in males, making them the sixth-most common cancer in men and the tenth-most common cancer overall, worldwide. Current guidelines do not recommend routine testing for human epidermal growth factor receptor (HER2/neu) expression on the biopsy specimens of patients with urothelial carcinoma. This study was aimed at determining the expression pattern of HER2/neu and its usefulness in muscle-invasive and nonmuscle-invasive urothelial carcinoma. HER2/neu expression was assessed in 89 specimens of urothelial cancer by immunohistochemistry (IHC), and equivocal cases were subjected to fluorescent in situ hybridization (FISH). On IHC for HER2/neu, 17.9% (7/39) of the muscle-invasive bladder cancers (MIBCs) showed a 3+ expression, whereas 22% (11/50) of the non-muscle invasive cancers were positive with a score of 3+. A significant correlation between HER2/neu status and muscle invasion could not be established in the current study (P = 0.74, Fisher’s exact test). Three cases of muscle-invasive (7.7%) and 2 cases (4%) among nonmuscle invasive cancers showed equivocal expression. All the cases with equivocal (2+) expression on IHC were subjected to FISH and none showed gene amplification on hybridization and were considered as negative. Overexpression of HER-2/neu was seen in 17.9% of MIBCs and 22% of non-MIBCs. There are no norms for routine testing of HER2/neu expression in the biopsy specimens of urothelial carcinoma. There is an unmet need to establish guidelines for HER2/neu scoring, similar to that for breast and gastric cancers, to determine the proportion of positive cases and help in identification of those who may benefit from targeted therapies.