International journal of clinical and experimental medicine

Histopathological alterations during breast carcinogenesis in a rat model induced by 7,12-Dimethylbenz (a) anthracene and estrogen-progestogen combinations.

PMID 25785005


Studies have shown that the development of breast cancer (BC) is a multi-step process that occurs sequentially from normal to usual hyperplasia, atypical hyperplasia, carcinoma in situ, and finally the invasive stages of carcinoma. Our study investigated the histopathological alterations in breast tissue in a Sprague-Dawley (SD) rat model induced by 7,12-Dimethylbenz (a) anthracene (DMBA) and estrogen-progestogen (E-P). Fifty rats were randomly divided into five groups (n = 10 each) and administered the E-P/DMBA combination. After the induction of BC, breast tissue samples were obtained from the rats and stained with hematoxylin-eosin (HE). Breast tissues from 10 rats and 10 human patients were obtained for comparison. The expression of P63, CK5/6 and CK34βE12 was observed and analyzed using the SPSS 17.0 software. The HE results showed ductal epithelial hyperplasia with forming a second lumen or papillary structure, atypical hyperplasia with atypical proliferative cells, forming a cross-bridge or cribriform structure in breast tissues from the rats samples. The IHC results showed that the expression of P63 was not significantly different between rat and human breast tissue (P > 0.05), but its expression in rat and human tissue was significantly different between UDH, ADH, DCIS and IDC (P < 0.01). A similar trend was observed for the expression of CK5/6 and CK34βE12 too. Thus, the findings in this model may reflect the histopathological changes that occur during the progression of human BC. Therefore, this model could be used for the establishment of BC models to investigate the prevention and treatment of BC.