The KIP/CIP family members p21^{Waf1/Cip1} and p57^{Kip2} 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 p57^Kip2 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.
['Zohny|Samir F|SF|', 'Baothman|Othman A|OA|', 'El-Shinawi|Mohamed|M|', 'Al-Malki|Abdulrahman L|AL|', 'Zamzami|Mazin A|MA|', 'Choudhry|Hani|H|']
D000328:Adult D014408:Biomarkers, Tumor D001943:Breast Neoplasms D050759:Cyclin-Dependent Kinase Inhibitor p21 D050761:Cyclin-Dependent Kinase Inhibitor p57 D019175:DNA Methylation D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008875:Middle Aged D011401:Promoter Regions, Genetic D018719:Receptor, ErbB-2
p21^{Waf1/Cip1} p57^{Kip2} Breast cancer clinicopathological factors gene promoter methylation