Sensitivity of HER-2/neu antibodies in archival tissue samples of invasivebreast carcinomas - Correlation with oncogene amplification in 160 cases

Overexpression and amplification of the HER-2 oncogene in patients with bre ast cancer has correlated with early onset of metastasis, resistance to hor monal therapy and some forms of chemotherapy, and shortened survival. There fore, evaluation of this putative prognostic or predictive factor seems cri tical. Because different antibodies are used for the detection of the 185-k d HER-2 oncoprotein, we studied the sensitivity of 3 frequently used antibo dies. Immunohistochemistry results were correlated with gene amplification level as assessed by fluorescence in situ hybridization. Protein overexpres sion was found in 17.2% and 12.5% of cases using antibodies against the ext ernal (TAB250) and internal (CB11) domains of the protein, respectively, an d in 38.0% of cases using a rabbit polyclonal antibody. Fluorescence in sit u hybridization was successful in all 160 tumors, and amplification was fou nd in 37 tumors (23.1%). The monoclonal antibody TAB250 had the lowest misc lassification rate, 9.6% (sensitivity, 67%, specificity, 97.5%).