Cell turnover in apocrine metaplasia of the human mammary gland epithelium:: apoptosis, proliferation, and immunohistochemical detection of Bcl-2, Bax, EGFR, and c-erbB2 gene products

Apocrine metaplasia is considered to be a benign lesion of human mammary epithelium. However, it is not known how apocrine differentiation develops, and whether there is a relationship with particular subtypes of mammary carcinoma. In order to investigate cell turnover in apocrine metaplasia, apoptosis was detected by terminal transferase nick-end-labelling, and Ki-67 was used as proliferation marker. Bcl-2, Bax, epidermal growth factor receptor (EGFR), and c-erbB2-encoded protein were detected by immunohistochemistry. The proliferative activity was low (<1%). Frequency and intraepithelial localization of apoptotic cells resembled those of normal mammary epithelium. Bax immunostaining was inconstant and weak, and Bcl-2 was not detectable in apocrine metaplasia. Immunoreactivity of the c-erbB2 gene product was membrane-bound and showed a moderate to strong intensity, whereas staining; for EGFR was weak and inconsistent. When compared with normal breast epithelium, apocrine metaplasia shows a regular cell turnover at a low rate, although the expression patterns of regulatory proteins are clearly altered. Our data suggest that changes in the expression of Bcl-2 or c-erbB2 protein do not result in a significant imbalance of apoptosis and proliferation, and thus should not be interpreted as indicator for increased risk of neoplastic transformation.