Affiliations: [a] Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia | [b] Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt | [c] General Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
Correspondence:
[*]
Corresponding author: Samir F. Zohny, Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia. E-mail:sfmz@hotmail.com
Abstract: 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.
Keywords: Breast cancer, p21^{Waf1/Cip1}, p57^{Kip2}, gene promoter methylation, clinicopathological factors
