CRITICAL DETERMINATION OF THE FREQUENCY OF C-ERBB-2 AMPLIFICATION IN BREAST-CANCER

Tissues from 323 methacarn-fixed and paraffin-embedded breast cancers were assessed for c-erbB-2 gene amplification by differential polymera se chain reaction (dPCR). The sensitivity of dPCR was ascertained usin g cell lines with c-erbB-2 amplification, and the relationship between dPCR ratio value and gene copy number was established. In clinical ma terial the technique was not affected by the DNA contribution of norma l tissue elements or by cancer DNA ploidy change. c-erbB-2 gene amplif ication was detected in 55% of invasive cancers and in 66% of in situ cancers. c-erbB-2 protein overexpression in breast cancer cells, as de termined by specific immunohistochemistry, was only detected in 11% of invasive cancers and 43% of in situ cancers. Comparisons show that a substantial number of cancers with c-erbB-2 amplification lack detecta ble protein overexpression. This illustrates the complex nature of c-e rbB-2 gene disregulation in cancer and suggests that multiple combinat ions of biological events and consequences are possible.