Rosen Daniel G, Yang Gong, Cai Kathy Qi, Bast Robert C, Gershenson David M, Silva Elvio G, Liu Jinsong
Departments of Pathology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):632-7.
The cyclin-dependent kinase inhibitor p27(kip1) regulates cellular progression from G(1) to S phase. Several studies have shown that loss of p27(kip1) protein expression is associated with disease progression in various malignancies. The purpose of this study was to evaluate the subcellular localization of this cyclin-dependent kinase inhibitor in a large cohort of primary ovarian carcinomas and compare the results with clinicopathologic variables and overall survival.
Subcellular localization of p27(kip1) was first assessed by Western blotting in nuclear and cytoplasmic extract from 13 cases of ovarian carcinoma. Subcellular localization of the p27(kip1) protein was evaluated using tissue microarrays containing 421 cases of ovarian carcinoma.
The presence of p27(kip1) in the cytoplasm regardless of the nuclear stain correlated strongly with late-stage disease (P < 0.03), extent of cytoreduction (P = 0.03), and shorter disease-specific survival (P < 0.0001).
Cytoplasmic localization of p27(kip1) predicts poorer prognosis in ovarian carcinoma, particularly in late-stage disease.
细胞周期蛋白依赖性激酶抑制剂p27(kip1)调节细胞从G1期到S期的进程。多项研究表明,p27(kip1)蛋白表达缺失与多种恶性肿瘤的疾病进展相关。本研究的目的是评估这种细胞周期蛋白依赖性激酶抑制剂在一大组原发性卵巢癌中的亚细胞定位,并将结果与临床病理变量和总生存期进行比较。
首先通过蛋白质印迹法在13例卵巢癌的细胞核和细胞质提取物中评估p27(kip1)的亚细胞定位。使用包含421例卵巢癌的组织微阵列评估p27(kip1)蛋白的亚细胞定位。
无论细胞核染色情况如何,细胞质中p27(kip1)的存在与晚期疾病(P < 0.03)、肿瘤细胞减灭程度(P = 0.03)及较短的疾病特异性生存期(P < 0.0001)密切相关。
p27(kip1)的细胞质定位预示卵巢癌预后较差,尤其是在晚期疾病中。