Clinical Significance of Cyclin D1 and p16 Protein Expression in Primary Breast Carcinoma

Shin, Myeong Jun; Lee, Soo Jung; Suh, Bo Yang; Kwun, Koing Bo; Kim, Dong Suk

Abstract

BACKGROUND: There is experimental evidence that overexpression of cyclin D1 accelerates the entry of cells into the S-phase, but that p16 inhibits the CDK4 and CDK6 by binding in competition with the cyclin D1. Previous attempts to correlate cyclin D1 amplification with prognoses have frequently drawn associations with adverse outcome or a more aggressive phenotype. Recently, overexpression of cyclin D1 has been associated with improved relapse-free survival and overall survival rates. To elucidate whether the expressions of the cyclin D1 and the p16 protein might be of clinical value as prognostic factors, we used the chi-square test to compare the immunoreactivities of the cyclin D1 and the p16 proteins with the histopathologic findings and with such known prognostic factors as the estrogen receptor, progesteron receptor, c-erbB-2, p53 and Ki-67.
METHODS
The expressions of the cyclin D1 and the p16 proteins were analysed using immunohistochemical methods in formalin-fixed and paraffin-embedded tissue samples of 340 invasive breast carcinomas accumulated between 1990 to 1997 at Yeungnam University Hospital. Disease-free survival and overall survival were compared to cyclin D1 and p16 status by using the Kaplan-Meier method.
RESULTS
Nuclear immunoreactivities of the cyclin D1 and the p16 proteins were detected in 75.6% (257/340) and 70.5% (208/295) cases, respectively. Cyclin D1 was found to have a strong correlation with lower histologic grade, lower nuclear grade, lower mitotic index, and lower Scarff-Bloom-Richardson (SBR) and Modified-Scarff-Bloom-Richardson (MSBR) grade (p<0.05). Cyclin D1 was more common in non-ductal carcinomas than ductal carcinomas, though this difference did not reach statistical significance. Cyclin D1 was also correlated with positive estrogen receptor, negative c-erbB-2, and positive p16 protein. P16 protein expression was found to have a correlation with positive estrogen receptor and progesterone receptor. The expressions of the cyclin D1 and the p16 proteins were not significantly correlated with overall survival and disease-free survival.
CONCLUSIONS
These results show that the expressions of the cyclin D1 and the p16 proteins can not be used as prognostic indicators in primary breast carcinomas.