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

Lee, Soo Jung; Kwun, Koing Bo; Kim, Dong Suk

Abstract

BACKGROUND: There is experimental evidence that overxpression of cyclin D1 accelerates the entry of cells into S-phase, but that p16 inhibits the CDK4 and CDK6 by binding in competition with 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 expression of cyclin D1 and p16 protein might be of clinical value as prognostic factors, the immunoreactivity of cyclin D1 and p16 protein were compared by the chi-square test with histopathologic findings and such known prognostic factors as estrogen receptor, progesteron receptor, c-erbB-2, p53 and Ki-67.
METHODS
The expression of cyclin D1 and p16 protein was 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 Kaplan-Meier method.
RESULTS
The nuclear immunoreactivity of cyclin D1 and P16 protein was 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, lower SBR and MSBR grade(p<0.05). Cyclin D1 was more common in non-ductal carcinomas than ductal carcinomas, though this 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 expression of cyclin D1 and p16 protein was not significantly correlated with overall survival and disease free survival.
CONCLUSIONS
These results showed that expression of cyclin D1 and p16 protein could not be used as a prognostic indicator in primary breast carcinoma.