DNA, RNA and Immunohistochemical Characterization of the HER-2/neu Oncogene in Transitional Cell Carcinoma of the Bladder

Abstract

HER-2/neu overexpression appears to play a role in determining the malignant potential of some human cancers. To date, no urothelial malignancies appear to have been evaluated for HER-2/neu DNA amplification, mRNA expression and protein overproduction. By Southern hybridization we detected DNA amplification and a possible structural rearrangement of the HER-2/neu oncogene in one of 12 bladder tumors. A 14 kb DNA fragment in addition to the expected 12.5 Kb fragment was found. Additionally, the HER-2/neu oncogene was amplified sixfold in the tumor compared to placental DNA. Five of 14 (36%) bladder tumors overexpressed HER-2/neu mRNA three to 38-fold compared to normal urothelium. HER-2/neu overexpression occurred in superficial and invasive tumors. Immunohistochemical analysis was performed on the one tumor with DNA amplification and the 14 tumors evaluated for mRNA expression. The tumor with DNA amplification and three of the five tumors with HER-2/neu mRNA overexpression stained positively for the p185HER-2/neu protein. These findings suggest that DNA amplification occurs infrequently in bladder cancer. Thirty-six percent of bladder cancers overexpress HER-2/neu mRNA. Immunohistochemical analysis with a p185HER-2/neu polyclonal antibody, on formalin fixed, paraffin embedded tissue, was specific for HER-2/neu overexpression but not as sensitive as Northern analysis.