Expression of p21(Waf1), p27(Kip1) and cyclin D1 proteins in breast ductalcarcinoma in situ: Relation with clinicopathologic characteristics and with p53 expression and estrogen receptor status

p21(Waf1) (p21), p27(Kip1) (p27) and cyclin D1 have recently been reported as useful prognostic markers for patients with breast carcinoma. However, s tudies on these cell cycle regulators in ductal carcinoma in situ (DCIS) ha ve been extremely limited. Therefore, we studied the immunohistochemical ex pression of p21, p27 and cyclin D1 proteins in 49 DCIS cases and compared t he findings with the clinicopathologic parameters (age, tumor size, gross t ype, histologic type, histologic grade, necrosis and mitotic index), p53 an d estrogen receptor (ER) status. A significant correlation was found betwee n positive p21 immunoreactivity (67.3% of the cases) and well-differentiate d histologic grade, non-comedo type, ER-positive and p53-negative (p53-) st atus. DCIS with p21+/p53- is likely to be the non-comedo type. The overexpr ession of cyclin D1 (59.2% of the cases) correlated positively with the ER expression (P = 0.001). The p27 protein expression (46.9% of the cases) cor related with the cyclin D1 immunopositivity (P = 0.0003) and ER expression (P = 0.005). No significant associations were seen in the p27 or cyclin D1 expression and other clinicopathologic parameters. Our results suggest that p21 might be more related to the useful biologic markers in DCIS than p27 or cyclin D1. The significant positive association between p21, p27 or cycl in D1 and ER status, and close association of p27 and cyclin D1 expression might be implicated in the tumor biology of DCIS.