RESUMEN
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.
Asunto(s)
Apoptosis/fisiología , Mama/patología , Epitelio/patología , Mama/fisiología , División Celular/fisiología , Femenino , Humanos , Etiquetado Corte-Fin in Situ , Antígeno Ki-67/análisis , Metaplasia , Proteínas Proto-Oncogénicas c-bcl-2/análisisRESUMEN
Cell proliferation, apoptosis, and the expression of Bcl-2 and Bax were investigated in breast tissue of healthy premenopausal women in order to study the effect of the menstrual cycle and reproductive history on the cell turnover in the non-lactating mammary gland epithelium. Immunohistochemistry was used to detect the proliferation-associated antigen Ki-67, as well as Bcl-2 and Bax. Apoptotic cells were identified by enzymatic labelling of fragmentized DNA (TUNEL-technique) and morphologic analysis. Consistent with published data, the proliferative activity and the frequency of apoptotic events as detected by morphologic analysis was higher in the luteal than in the follicular phase of the menstrual cycle. Parity, lactation, and age correlated with lower proliferative activity, whereas the frequency of apoptosis was not significantly influenced by the reproductive history. Staining patterns for Bax and Bcl-2 showed characteristic changes due to the menstrual cycle with a maximum of immunoreactivity for Bcl-2 in the follicular phase and for Bax in the luteal phase. However, there was no statistically significant association between Bcl-2/Bax immunoreactivity and menstrual cycle or reproductive parameters. We conclude that other molecular pathways than the Bax/Bcl-2 antagonism may additionally be involved in the regulation of apoptotic cell death in the breast epithelium. Knowledge of the entire complexity of apoptosis regulation is necessary to understand the observed effects of parity and lactation on mammary epithelial biology, and possibly to be able to influence pathological processes caused by an imbalance between cell renewal and elimination.