Expression of p21(waf1/cip1) protein in transitional cell bladder tumours and its prognostic value
Expression of p21(waf1/cip1) protein in transitional cell bladder tumours and its prognostic value
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DOI：
10.1159/000019721
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发表时间：
1998-09-01
期刊：
影响因子：
23.4
通讯作者：
Kosma, VM
中科院分区：
文献类型：
--
作者：
Lipponen, P;Aaltomaa, S;Kosma, VM
目的：p21（waf 1/cip 1）蛋白是一种细胞周期蛋白依赖性激酶抑制剂，能够通过与增殖细胞核抗原（PCNA）相互作用抑制DNA复制而将细胞阻滞在G（1）期。对人膀胱癌细胞系的实验分析表明，p21可能被认为是一种肿瘤抑制基因，因为它能够像p53一样诱导凋亡。p21（waf 1/cip 1）在膀胱癌中的表达及其预后价值目前研究尚不完全。研究方法：应用免疫组化方法对186例原发性膀胱移行细胞肿瘤石蜡包埋标本中p21蛋白的表达进行了分析。免疫组化分析的结果与已知的预后因素和完整的长期临床随访数据（超过11年）有关。结果如下：p21（waf 1/cip 1）蛋白的表达与肿瘤的DNA倍体、S期细胞比例、有丝分裂指数、凋亡指数、形态计量学核因子、p53和PCNA蛋白的表达显著相关，而与肿瘤的分级和TNM分期无关。单因素生存分析显示p21（waf 1/cip 1）蛋白表达与预后无明显相关性。独立的预后因素是T分类，乳头状状态和有丝分裂指数。结论：结果表明，尽管p21（waf 1/cip 1）蛋白表达与细胞增殖、凋亡和p53表达的指标相关，但其在膀胱癌中的预后价值并不比已经建立的预后因素更好。
Objectives: p21(waf1/cip1) protein is a cyclin-dependent kinase inhibitor able to arrest the cell at the G(1) phase by inhibiting DNA replication through interaction with proliferating cell nuclear antigen (PCNA). Experimental analyses of human bladder cancer cell lines show that p21 might be considered a tumour suppressor gene since it is able to induce apoptosis like p53. The prognostic value and expression of p21(waf1/cip1) is incompletely studied in bladder cancer at present. Methods: The expression of p21 protein was immunohistochemically analysed in paraffin-embedded specimens of 186 patients with primary transitional cell bladder tumours. The results of immunohistochemical analysis were related to known prognostic factors and complete long clinical follow-up data (over 11 years). Results: The expression of p21(waf1/cip1) protein was significantly related to DNA ploidy, S phase fraction, mitotic index, apoptotic index, morphometric nuclear factors, and the expression of p53 and PCNA proteins, whereas it was unrelated to grade or TNM classification. In univariate survival analysis, the expression of p21(waf1/cip1) protein was not significantly related to prognosis. Independent prognostic factors were T category, papillary status and mitotic index. Conclusion: The results indicate that although the expression of p21(waf1/cip1) protein is related to indicators of cell proliferation, apoptosis and p53 expression, it has no better prognostic value than already established prognostic factors in bladder cancer.