STABILITY OF HER-2 NEU EXPRESSION OVER TIME AND AT MULTIPLE METASTATIC SITES/

Background: Amplification and over-expression of the HER-2/neu oncogen e (also known as c-erbB-2) occurs in 20%-30% of invasive breast carcin omas. The extent to which HER-2/neu expression changes over time in as sociation with tumor progression or is heterogeneous at different meta static sites has received only limited study. Purpose: Our purpose was to determine whether primary tumors differ from metastases in HER-2/n eu protein content or whether metastases are heterogeneous in regard t o HER-2/neu expression. Methods: In a retrospective study, we examined tumor tissue obtained at autopsy from two to rive metastatic organ si tes in each of 30 patients who died with metastatic breast carcinoma. Using an immunoperoxidase technique, we stained archival formalin-fixe d, paraffin-embedded tissue sections with a monoclonal antibody to the 185-kilodalton protein product (p185) of the HER-2/neu gene. Results: 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 othe r two showed strong immunoreactivity. In 14 cases, we were able to obt ain paraffin blocks from the original biopsy or surgical resection of the primary breast lesion. For these 14 patients, the average length o f time between initial diagnosis and death was 4 years (range, 2-9). T here was good correlation between results from autopsy and original su rgical tissues. Conclusions: Expression of HER-2/neu appears to be rel atively stable over time and is generally congruent at different metas tatic sites. Implications: The fact that p185 immunoreactivity is rare ly heterogeneous is encouraging, both for the potential use of HER-2/n eu-related proteins as serum tumor markers and for innovative therapie s targeted at p185 expression.