c-erbB-2 over-expression in amplified and non-amplified breast carcinoma samples

Abstract

We investigated c‐erbB‐2 oncogene amplification and over‐expression in 79 invasive breast carcinoma samples using fluorescence in situ hybridization (FISH) and immuno‐histochemistry, with the aim of studying relationships between neoplasms over‐expressing c‐erbB‐2 with or without amplification and bio‐pathological parameters used in clinical breast cancer. Nineteen samples showed amplification, and all of these were positive by immuno‐histochemistry. Moderate or intense immunostaining was present in a further 22 samples without c‐erbB‐2 amplification and was not related to any increased number of c‐erbB‐2 signals: 15 samples exhibited chromosome 17 polysomy, 3 monosomy and 4 no FISH abnormalities. Thirty‐eight samples were immunonegative: 18 exhibited chromosome 17 polysomy, 9 monosomy and 11 no alterations. Samples having c‐erbB‐2 over‐expression associated with amplification showed DNA aneuploidy and hormonal receptor loss to a greater extent than those expressing c‐erbB‐2 without amplification or immunonegative samples (χ² test, p = 0.007, 0.008 and 0.008, respectively). The proliferation rate, detected by Ag‐NOR staining, was highest in amplified samples (Kruskal Wallis test, p = 0.009). Our results indicate that tumours showing both c‐erbB‐2 over‐expression and amplification exhibit more aggressive biological characteristics than those with only over‐expression or immunonegative tumours. Since both c‐erbB‐2 amplification and over‐expression have been related to negative responses to chemotherapy and poor prognosis, these differences might have clinical implications. The combination of FISH and immuno‐histochemistry may be helpful to achieve this aim. Int. J. Cancer (Pred. Oncol.) 84:273–277, 1999.