There is experimental evidence that overexpression 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.

The expression of cyclin D₁ and p16 protein was analyzed 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.

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.

These results showed that expression of cyclin D₁ and p16 protein could not be used as a prognostic indicator in primary breast carcinoma.