p21/WAF1/Cip1 expression in invasive ductal breast carcinoma: relationship to p53, proliferation rate, and survival at 5 years

Abstract

The p21/WAF1/Cipl antibody, DCS-60, was characterized by means of immunoblotting and immunofluorescence on a variety of human breast cancer cell lines. Heterogeneous staining of nuclei was observed with strong staining of cells in early G1. p21/WAF1/Cipl expression in invasive ductal, not otherwise specified breast carcinomas was determined using immunohistochemistry with this antibody and computerized image analysis. Two hundred and twenty-two tumors, including 130 from patients with no axillary node involvement, were examined. p21-positive tumor cell nuclei were found in 30% of the breast carcinomas. The percentage of tumor cell nuclei that were positive ranged from less than 1% to greater than 10%. In the whole cohort of patients, p21 expression was significantly associated with a low histological grade. In the node-negative group, there was a significant negative correlation between p21 positivity and a high (>10%) MIB-1 score. The mean MIB-1 score was significantly lower in p21-positive tumors in the whole cohort of patients (P=0.03) and in the nodenegative group (P=0.02). No association was found between p21 expression and overall survival at 5 years. With respect to p21/p53 phenotype, the significant difference in survival was noted only for the group of patients treated with adjuvant chemotherapy. The p21- p53+ phenotype had the worst survival (58% surviving 5 years), while the p21+ p53- phenotype had good survival (83% surviving 5 years; P<0.05). The results seem to suggest a correlation between p21/p53 phenotype and response to adjuvant chemotherapy.

Correlation between pathological data and the RNA expression of p53 or p53-targeted genes in primary invasive ductal breast carcinomas: A preliminary study

“…It has been shown that concomitantly with DBC growth and invasion of the basement membrane, Hdm2 protein levels increase, while p53-induced proteins including the p21 waf-1 cell cycle inhibitor and TSP-1 are reduced (4)(5)(6)(7)(8). The findings reported above suggested earlier that measuring the expression of p53 or its transcriptional targets could monitor human DBC progression, having a prognostic relevance.…”

“…The findings reported above suggested earlier that measuring the expression of p53 or its transcriptional targets could monitor human DBC progression, having a prognostic relevance. However, studies evaluating this possibility gave contrasting results (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). This could depend on the fact that DBC expression of p53 or its targeted molecules was assayed mostly at the protein level.…”

Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway

“…Uncontrolled cell division and malignancy occur due to an unchecked or hyper-activated cyclin D1/CDK4 complex. Normal p21 function plays a crucial role in the induction of apoptosis and cell cycle G1/S transition checkpoints in human and murine cells following DNA damage (40), and the downregulation of p21 expression is associated with the promotion of tumor formation and a poor prognosis in many types of cancer (41). In this study, we found that NC downregulated the expression of cyclin D1/CDK4 and upregulated the expression of p21 in vivo, suggesting that NC inhibited cancer cell proliferation by inducing arrest at the G1/S phase.…”

Tamoxifen-stimulated growth of breast cancer due to p21 loss

“…Our case report highlights a unique mechanism of tamoxifen growth stimulation whereby p21 loss leads to hyperphosphorylation of ER serine 118 via unopposed cyclin/CDK activity. Although loss of p21 expression in breast cancers can occur at high frequency (15), studies correlating loss of p21 expression with clinical outcome have been conflicting (38). One reason for this may be that loss of p21 is a predominant mechanism of acquired, but not de novo, tamoxifen resistance.…”