Bozdoğan Onder, Atasoy Pinar, Batislam Ertan, Başar M Murad, Başar Halil
Pathology Department, Kirikkale University Medical School, Kirikkale, Turkey.
Tumori. 2008 Jul-Aug;94(4):556-62. doi: 10.1177/030089160809400418.
Cyclin-dependent kinase inhibitors have important roles in the oncogenesis of various tumors including urothelial cancer. The aim of this study was to establish the importance of p57(Kip2), a unique cyclin-dependent kinase inhibitor, in the oncogenesis of bladder carcinoma. This article also focused on another cyclin-dependent kinase inhibitor, p27(Kip1), and telomerase enzyme and examined the relationship between these proteins.
Thirty-one patients with urothelial carcinomas of the bladder and 7 cases with normal urinary bladder mucosa were included in the study. Immunohistochemical study was performed by monoclonal antibodies of p27(Kip1), p57(Kip2), and the telomerase subunit (hTERT). All immunohistochemical preparations were evaluated by an immunohistochemical histological score.
p57(Kip2) and p27Kip1) expression were seen in all of the cases of normal mucosa. In carcinoma cases, 8 of 31 (25.8%) showed p57(Kip2) nuclear positivity and 20 of 31 (64.5%) expressed nuclear p27(Kip1). HSCOREs of carcinoma cases showed lower scores of nuclear p57(Kip2) and p27(Kip1) than normal mucosa, but only HSCOREs of nuclear p57(Kip2) (P = 0.001) showed statistical significance. Despite unknown significance, cytoplasmic p57(Kip2) and p27(Kip1) were also evaluated. Immunohistochemical analysis showed that carcinomas expressed higher HSCOREs of hTERT than normal mucosa, and there was a significant difference (P = 0.026) between muscle invasive carcinomas and normal mucosa.
The data showed that p57(Kip2) down-regulation along with p27(Kip1) is a well-established feature of urothelial carcinoma. Probably, this down-regulation of cyclin-dependent kinase inhibitors supports the proliferation phase of oncogenesis. In the study, we also showed that hTERT expression was up-regulated in higher stages of urothelial carcinoma.
细胞周期蛋白依赖性激酶抑制剂在包括尿路上皮癌在内的各种肿瘤的发生发展中具有重要作用。本研究的目的是确定一种独特的细胞周期蛋白依赖性激酶抑制剂p57（Kip2）在膀胱癌发生中的重要性。本文还聚焦于另一种细胞周期蛋白依赖性激酶抑制剂p27（Kip1）和端粒酶，并研究了这些蛋白之间的关系。
本研究纳入了31例膀胱尿路上皮癌患者和7例正常膀胱黏膜病例。采用p27（Kip1）、p57（Kip2）和端粒酶亚基（hTERT）的单克隆抗体进行免疫组织化学研究。所有免疫组织化学标本均通过免疫组织化学组织学评分进行评估。
在所有正常黏膜病例中均可见p57（Kip2）和p27（Kip1）表达。在癌病例中，31例中有8例（25.8%）显示p57（Kip2）核阳性，31例中有20例（64.5%）表达核p27（Kip1）。癌病例的HSCOREs显示核p57（Kip2）和p27（Kip1）的评分低于正常黏膜，但只有核p57（Kip2）的HSCOREs（P = 0.001）具有统计学意义。尽管意义不明，但也对细胞质p57（Kip2）和p27（Kip1）进行了评估。免疫组织化学分析显示，癌组织中hTERT的HSCOREs高于正常黏膜，且肌肉浸润性癌与正常黏膜之间存在显著差异（P = 0.026）。
数据表明，p57（Kip2）与p27（Kip1）一起下调是尿路上皮癌的一个既定特征。细胞周期蛋白依赖性激酶抑制剂的这种下调可能支持肿瘤发生的增殖阶段。在本研究中，我们还表明hTERT表达在尿路上皮癌的较高阶段上调。
