Korean J Pathol.
2000 Apr;34(4):288-299.
Significance of Expression of p16, Cyclin D1, Rb, and p53 Protein and Correlation with
Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast
- Affiliations
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- 1Departments of Pathology, Chosun University College of Medicine, Kwangju 501-759, Korea.
- 2Departments of General Surgery, Chosun University College of Medicine, Kwangju 501-759, Korea.
Abstract
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The retinoblastoma (Rb)/cyclin D1/p16 pathway is an important constituent of cell cycle
regulation. Perturbations in this pathway due to a variety of genetic aberrations have been
reported in many human cancers including breast cancer. We examined the significance of
immunoexpression of p16 protein, cyclin D1 protein, Rb protein (pRb), and p53 protein in 128 cases
of invasive breast carcinoma. The results were correlated with survival rate and clinicopathological
variables, including age, histologic grade, lymph node status, tumor size, estrogen receptor (ER),
and progesterone receptor (PR) content. Abnormal expressions of p16 and pRb which were defined
as negative staining were seen in 21% and 43% of tumors, respectively. There was a significant
inverse relationship between p16 and pRb expression. There was no correlation between p16
staining and any other parameters, including survival rate, cyclin D1, p53, and clinicopathologic
variables. Surprisingly, there was a trend for tumors which were positive for pRb to be grade III
ductal carcinomas. Cyclin D1 positivity was noted in 46% of cases. The expression of cyclin D1
protein was significantly higher in lower histologic grade, higher ER and PR expression. The
expression of p53 protein showed a significant correlation with high tumor grade. In a Cox
multivariate analysis, neither p16, pRb, cyclin D1 nor p53 was an independent predictor, but tumor
size and lymph node status were independent predictors of patient outcome.