The aim of the study is to investigate the alterations in expression of estrogen receptor alpha (ER), progesterone receptor (PgR), c-erbB2 gene (HER-2/neu), and P53 protein in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinomas (IDC), and the association between their expression and clinicopathologic findings. The mastectomy specimens of 520 cases containing both DCIS and IDC were examined. The expression of ER, PgR, HER-2/neu, and P53 proteins were examined by immunohistochemistry. Linear regression was used to investigate the correlation among ER, PgR, HER-2/neu, P53 protein expression, and the clinicopathologic factors. There was a significant decrease of ER and PgR expression in IDC compared to DCIS (32.81 vs. 21.05%, chi(2) = 4.45, P = 0.035; 26.56 vs. 15.57%, chi(2) = 4.82, P = 0.028, respectively). In contrast, there was a significant increase of HER-2/neu expression in IDC compared to DCIS (10.94 vs. 21.27%, chi(2) = 3.88, P = 0.049). However, there was no significant difference in expression of p53 between DCIS and IDC. In both DCIS and IDC, a significant positive correlation was observed between ER and PgR receptor expression (r = 0.67, P = 0.00; r = 0.56, P = 0.00, respectively). In conclusion, these findings substantiate the notion that breast cancer progression is often associated with alterations in expressions of ER, PgR, and HER-2/neu. The underlying mechanisms of these alterations need further investigation.