Stability of HER-2/neu Expression Over Time and at Multiple Metastatic Sites

Abstract

Amplification and over-expression of the HER-2/neu oncogene (also known as c-erbB-2) occurs in 20%-30% of invasive breast carcinomas. The extent to which HER-2/neu expression changes over time in association with tumor progression or is heterogeneous at different metastatic sites has received only limited study. Our purpose was to determine whether primary tumors differ from metastases in HER-2/neu protein content or whether metastases are heterogeneous in regard to HER-2/neu expression. In a retrospective study, we examined tumor tissue obtained at autopsy from two to five metastatic organ sites in each of 30 patients who died with metastatic breast carcinoma. Using an immunoperoxidase technique, we stained archival formalin-fixed, paraffin-embedded tissue sections with a monoclonal antibody to the 185-kilodalton protein product (p185) of the HER-2/neu gene. The tissue from eight of 30 patients showed strong diffuse reactivity for p185 at all metastatic sites examined. Tissues from six patients showed faint staining and tissues from 15 were negative, again with a congruent staining pattern. A single case showed discordant staining, in that two of four metastases showed faint staining, whereas the other two showed strong immunoreactivity. In 14 cases, we were able to obtain paraffin blocks from the original biopsy or surgical resection of the primary breast lesion. For these 14 patients, the average length of time between initial diagnosis and death was 4 years (range, 2-9). There was good correlation between results from autopsy and original surgical tissues. Expression of HER-2/neu appears to be relatively stable over time and is generally congruent at different metastatic sites. The fact that p185 immunoreactivity is rarely heterogeneous is encouraging, both for the potential use of HER-2/neu-related proteins as serum tumor markers and for innovative therapies targeted at p185 expression.