p27Kip1 and Ser10-phosphorylated p27Kip1 in breast cancer: clinical significance and expression

Abstract

Wei Song,1* Ruilian Xie,2* Aiyu Zhu,1 Yumei Xu,1 Yaqin Shi,3 Yan Shen,3 Wenwen Zhang,3 Fang Yang,3 Xiaoxiang Guan1,3 1Department of Medical Oncology, Jinling Hospital, Southern Medical University, Guangzhou, 2Department of Medical Oncology, The First Affiliated Hospital of Gannan Medical College, Ganzhou, 3Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: The protein p27 (p27Kip1) is a member of the cyclin-dependent kinase inhibitor family, which negatively regulates cell cycle progression, and the phosphorylation of p27 has been proven to affect its stability and nuclear export. Clinical studies on the relation between p27 and phosphorylated p27 (p-p27Ser10) in breast invasive ductal carcinomas are still scarce. Methods: We examined the expression of p27 and p-p27Ser10 using immunohistochemistry in 107 breast invasive ductal carcinomas and analyzed the relationship of these biomarkers and tumor characteristics. Results: Of the 107 tumor samples, 38.3% (41 of 107) overexpressed p27 and 64.5% (69 of 107) overexpressed p-p27Ser10. Analysis of correlation with clinical characteristics showed that high expression level of p-p27Ser10 was linked to poor differentiation, advanced disease stage, and lymph node metastasis, whereas a contrary trend was observed for p27 (all P<0.05). In addition, the expression of p-p27Ser10 was significantly higher in malignant tumors than in adjacent tissues, while p27 showed the opposite trend. Also, there were different levels of p27 and p-p27Ser10 in different types of breast cancer. Conclusion: p27 and p-p27Ser10 are involved in the development of invasive ductal carcinoma and are potential indicators to judge the degree of malignancy as well as recurrence and metastasis. Keywords: breast cancer, p27, p-p27Ser10, Ki67, ERα, PR, Her2