Immunohistochemical localization of c-erbB-2 in human breast carcinomas

This study was carried out to assess the utility of antibodies raised to synthetic peptides of the predicted sequence of the c-erbB-2 gene product to identify immunocytochemically those tumours overexpressing this putative transmembrane receptor. Staining with rabbit antiserum 21N gave the best correlation with gene amplification and did not stain the membrane of any of the normal tissues at the dilution which strongly stained the amplified tumours. No significant correlation was found with lymph node involvement, epidermal growth factor receptor status or with oestrogen receptor levels. Of the 12 out of 34 cases which demonstrated c-erbB-2 gene amplification in the primary tumour, two had lymph node metastases which were also positive immunocytochemically. Fourteen other cases which had lymph node metastases were negative in the primary tumour and in the metastases. These tumours all showed strong membrane positivity. A comparison of modified methacarn and formol saline fixation demonstrated an increased sensitivity with the former, but the staining pattern was unaltered. This small but extensively studied group of cases has indicated that increased c-erbB-2 protein can be identified routinely in fixed tissue sections, making it possible to carry out extensive studies to look for clinical correlates, but also to assess the stage in tumour progression at which the increased expression occurs and whether it correlates with any potentially premalignant condition.