The Differential p53 Expression in Breast Cancer Development and the Correlation to Proliferative Index of Breast Cancer

Lee, Gyu Ho; Ahn, Sei Hyun; Gong, Kyung Yub; Lee, Moo Song

Abstract

p53 plays an important function as a negative regulator of cell growth and also inhibits transformation. It has been hypothesized that p53, acting as a control gene at a G1 check point, may detect DNA damage, slow the cell devision, and allow time for DNA repair. If damage is irreparable, the cell may be driven down into the apoptotic pathway, thus preventing replication of defective cells. In this retrospective study, we investigated the correlation between p53 protein expression by IHC staining and benign breast disease with or without atypical ductal hyperplasia, DCIS and invasive breast cancer. Also We analyzed the association between p53 protein expression and the following prognostic parameters in breast cancer patients; age, tumor size, axillary node involvement, stage, histologic grade, estrogen receptor, and progesteron receptor, and DNA ploidy. And, we investigated the correlation between p53 protein expression and the proliferative index of S phase fraction in diploid breast cancer. The results were as follows ; 1) In histopathological classification, none out of ten benign breast diseases, none out of seventeen fibrocystic disease with atypical ductal hyperplasia patients were p53 protein positive, 3 out of fifteen DCIS (20%), 29 out of eighty-six (34%) invasive breast cancer patients were p53 protien positive.2) There were no significant differences between p53 positivity and age, tumor size, axillary node involvement, stage, histologic grade, ER and PGR status, and DNA ploidy by Fisher's exact test with chi-squre test for trend, in invasive breast cancer. (n=86) 3) In diploid tumor (n=35), statistically significant differences were noted such that high S-phase fraction tumor revealed increased p53 positivity. (p<0.05) We have found that immunopositivity for p53 was detected in 20% of in situ carcinoma, suggesting that p53 mutation can be acquired early in malignant progression. We have also found that there is a strong direct correlation between the amount of mutant protein and tumor proliferation rate. These results are consistent with the hypothesis that wild-type p53 is involved in suppression of the cell cycle.