The KIP/CIP family members p21Waf1/Cip1 and p57Kip2 as diagnostic markers for breast cancer

OBJECTIVE: We examined the expression status of p21(Waf1/Cip1) and p57(Kip2) in breast cancer as well as their relationship with clinicopathological factors. Moreover, the diagnostic value of gene promoter methylation of p21(Waf1/Cip1) and p57(Kip2) was assessed in breast cancer patients. METHODS: This study involved 85 patients diagnosed with breast cancer and 36 patients with benign breast lesions. The expression of p21(Waf1/Cip1) and p57(Kip2) in cell lysates was analyzed by ELISA and Western blot, respectively. The gene promoter methylation of p21(Waf1/Cip1) and p57(Kip2) was examined in cell lysates by methylation specific PCR. RESULTS: p21(Waf1/Cip1) expression was higher while p57(Kip2) level was lower in breast cancer patients compared to patients with benign breast lesions. The combined use of p21(Waf1/Cip1) and p57(Kip2) provided sensitivity and specificity of 82.35% and 86.11%, respectively. None of the malignant and benign breast tumors were found to be hypermethylated at p21(Waf1/Cip1) gene promoter. However, aberrant methylation of p57(Kip2) gene promoter was detected in 49 of 85 (57.65%) of breast cancer tumors. High p21(Waf1/Cip1) level was associated with high grade, late stages and lymph node involvement, whereas low p57(Kip2) level was correlated with high grade and HER2 overexpressing breast cancer. Moreover, hypermethylated p(57Kip2) gene promoter was associated with high grade. CONCLUSION: Our findings show that the overexpression of p21(Waf1/Cip1), down-expression of p57(Kip2) and gene promoter methylation of p57(Kip2) could be considered as promising diagnostic markers for breast cancer.