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 established. To date, the expression of erbB-4 in breast tissue has been determined in only a few cases and, to the best of our knowledge, its amplification has not been examined. We therefore used the double differential polymerase chain reaction (ddPCR) for determination of the amplification profile of erbB-4 and erbB-2, another gene from the ErbB family, in human primary breast cancer specimens. We examined the amplification of the genes in 20 normal breasts and 176 invasive breast cancer samples. Amplification of erbB-2 was detected in 19% and erbB-4 in 13% of the samples studied. Co-amplification of the two oncogenes was found in only five out of 176 samples. Human breast cancer-derived cell lines in most cases overexpress both erbB-2 and erbB-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 overexpression, without overexpression of erbB-4, were also reported (Wosikowski et al., 1997. Clin. Cancer Res. 3, 2405-2414). At the gene level, we found 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 estrogen receptor activity and direct correlation with the tumor size were found. Due to these correlations, erbB-4 oncogene amplification can be assumed to be of prognostic or predictive value in the diagnosis of breast cancer.