Amplification and over-expression of erbB-2 oncogene in primary human breast tumors

Abstract

erbB-2 is a growth factor receptor gene, and it's product, p185, has tyrosine kinase activity and can transform NIH3T3 cell when overexpressed. erbB-2 oncogene has been reported to be amplified frequently in various human tumors of epithelial origin, such as breast, ovary and stomach. In breast cancer, the amplification and overexpression of erbB-2 protein, p185, have been implicated as parameters for prognosis. In this study, we analyzed 72 primary breast tumors obtained from Korean patients for gene amplification and mRNA over-expression, and 114 tumor tissue sections from paraffin blocks were analyzed for p185 expression using anti-p185 antibody. Ten (13.9%) of 72 DNA samples from primary breast tumors contained multiple copies of erbB-2 gene, ranging from 2 to 27. RNAs were prepared from 23 tumors among 72 tumors, of which 4 (17.4%) had increased amount of erbB-2 mRNA. Thirty-eight percent (43 of 114) of paraffin-embedded tissue sections were strongly reactive to the anti-p185 polyclonal antibody. No p185 was detectable in 37% ( 42 of 114) sections and the rest were weakly stained. Seventy percent (7 of 10) of tumors containing amplified erbB-2 gene were positive for p185 expression. B.ut, 37% (20 of 54) of tumors with single gene copy were strongly reactive to anti-p185 antibody. These results could explain the higher rate of protein expression than gene amplification of erbB-2 in primary breast tumors. We also observed mRNA over-expression in 2 of 15 tumors with single copy erbB-2 gene, and furthermore, strong expression of p185 protein in 4 of 15 tumors without increased mRNA expresseion. These suggest that other mechanisms than gene amplification andlor mRNA over-expression for the over-production of p185 in primary breast tumors may exist.