Immunohistochemical Analysis of Abnormal p16INK4A Protein Expression in Human Breast Cancer

Song, Tae Jin; Moon, Jeong Seok; Lee, Eun Suk; Lee, Jae Bok; Choi, Won Jun; Chae, Gi Bong; Mok, Young Jae; Bae, Jeoung Won; Won, Nam Hee; Koo, Bum Hwan

Abstract

BACKGROUND: The p16 protein is a cyclin-dependent kinase inhibitor (CDKI) that inhibits cell cycle progression from phase G1 to phase S in the cell cycle. Many p16 gene mutations have been noted in many cancer-cell lines and in some primary cancers. These mutated genes caused abnormal or aberrant expression of the p16 protein, which might have contributed to the malignant progression of the cells by deranging the cell cycle. This study was to examine the abnormal or aberrant expression of the p16 protein in breast cancer tissue by using p16 protein specific immunohistochemical staining.
METHODS
p16-protein-specific immunohistochemical staining was performed on 31 breast-cancer tissue samples. Twenty-four cases among the 31 tissue staining slides simultaneously showed a normal breast-tissue portion on the same staining slide. Microscopic photographs of both the breast-cancer and the normal- tissue portion were taken at the same magnification to compare the statistically analyzed fraction of red or brown colored p16 stained nuclei.
RESULTS
In the breast cancer tissue, 7 (22.6%) showed totally negative, with less than 5% of the nuclei staining. The completely negative cases were not related to the stage of the disease (p=0.096) or to the histopathologic grade (p=0.20). The staining ratios of the breast-cancer tissue and the normal tissue were 26.2 ( +/- 18.7)% and 72.4 ( +/- 18.8)%, respectively. In the breast-cancer tissue, the ratio of expression of the p16 protein was significantly lower than in the normal tissue (p=0.001).
CONCLUSIONS
In the carcinogenesis of some breast cancers, low expression of the p16 protein may play an important role in the unlimited proliferation of tumor cell due to a loss of the cell-cycle-regulating role of the p16 protein.