Amplification of erbB-4 oncogene occurs less frequently than that of erbB-2 in primary human breast cancer

ErbB-4 protein is a recently discovered member of the ErbB family. The role of ErbB-4 protein in mammary-gland tissue has not been definitively establ ished. To date, the expression of erbB-4 in breast tissue has been determin ed in only a few cases and, to the best of our knowledge, its amplification has not been examined. We therefore used the double differential polymeras e chain reaction (ddPCR) for determination of the amplification profile of erbB-4 and erbB-2, another gene from the ErbB family, in human primary brea st cancer specimens. We examined the amplification of the genes in 20 norma l breasts and 176 invasive breast cancer samples. Amplification of erbB-2 w as detected in 19% and erbB-4 in 13% of the samples studied. Go-amplificati on of the two oncogenes was found in only five out of 176 samples. Human br east cancer-derived cell lines in most cases overexpress both erbB-2 and er bB-4 (Beerli et al., 1995. Mol. Cell Biol. 15, 6496-6505; Han et al., 1995. Proc. Natl. Acad. Sci. USA 92, 9747-9751), but data on separate erbB-2 ove rexpression, without overexpression of erbB-4, were also reported (Wosikows ki et al., 1997. Clin. Cancer Res. 3, 2405-2414). At the gene level, we fou nd that co-amplification of the genes in the case of human breast cancer is rare. Moreover, an inverse association of the erbB-4 amplification with es trogen receptor activity and direct correlation with the tumor size were fo und. Due to these correlations, erbB-4 oncogene amplification can be assume d to be of prognostic or predictive value in the diagnosis of breast cancer . (C) 1998 Elsevier Science B.V. All rights reserved.