p16INK4a and p21Waf1/Cip1 expression correlates with clinical outcome in vulvar carcinomas
p16INK4a and p21Waf1/Cip1 expression correlates with clinical outcome in vulvar carcinomas
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DOI：
10.1016/j.ygyno.2004.07.026
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发表时间：
2004-10-01
影响因子：
4.7
通讯作者：
Holm, R
中科院分区：
文献类型：
--
作者：
Knopp, S;Bjorge, T;Holm, R
客观的。细胞周期激酶抑制剂 p 16、p21 和 p27 的异常表达与多种人类恶性肿瘤的不良预后相关。然而，人们对其对外阴癌患者的临床影响知之甚少。因此，我们分析了更大范围的外阴鳞状细胞癌，并将结果与临床结果进行比较。方法。使用生物素-链霉亲和素-过氧化物酶方法和 OptiMax Plus 自动细胞染色系统，对总共 224 例外阴鳞状细胞癌的 p 16、p21 和 p27 表达进行免疫组织化学研究。结果。 69 例（31%）例中发现高 p16（大于或等于 5%）阳性核免疫染色，95 例（42%）例中检测到高 p21（任何染色）蛋白水平，170 例（76%）例中检测到低 p27（小于或等于 50% 阳性核）染色。 p 16 的高表达与较低的患者年龄和 p53 的低表达有关。 p16的高表达表明在多变量分析中预后较好（RR=0.5，95% CI=0.2-1.0）并且发生淋巴结转移的风险较低（OR=0.3，95% CI=0.2-0.7）。高水平的p21与FIGO I和II期患者的较短生存期显着相关（RR=3.4，95% CI=1.3-9.3）。我们发现 p27 的表达与任何临床病理变量之间没有显着相关性。结论。我们的研究表明 p 16 和 p21 免疫反应性与预后相关。低水平的 p 16 蛋白和高水平的 p21 蛋白与较短的疾病相关生存期相关。我们没有发现 p27 蛋白表达可用作外阴癌患者的预后指标。 (C) 2004 Elsevier Inc. 保留所有权利。
Objective. Aberrant expression of the cell cycle kinase inhibitors p 16, p21, and p27 has been associated with poor prognosis in a variety of human malignancies. Little is known, however, about their clinical impact in vulvar carcinoma patients. Thus, we analyzed a larger series of vulvar squamous cell carcinomas and compared the results with clinical outcome.Methods. A total of 224 vulvar squamous cell carcinomas were immunohistochemically investigated for expression of p 16, p21, and p27 using the biotin-streptavidin-peroxidase method and the OptiMax Plus automated cell staining system.Results. High p16 (greater than or equal to5%) positive nuclear immunostaining was found in 69 (31%) cases, high p21 (any staining) protein levels was detected in 95 (42%) cases, and low p27 (less than or equal to50% positive nuclei) staining was seen in 170 (76%) cases. High expression of p 16 was related to lower patient age and low expression of p53. High expression of p16 indicated abetter prognosis in the multivariate analysis (RR=0.5, 95% CI=0.2-1.0) and less risk of developing lymph node metastasis (OR=0.3, 95% CI=0.2-0.7). High level of p21 was significantly associated with shorter survival in patients staged FIGO I and II (RR=3.4, 95% CI=1.3-9.3). We found no significant correlation between the expression of p27 and any of the clinicopathological variables.Conclusions. Our study indicates a prognostic relevance for p 16 and p21 immunoreactivity. Low level of p 16 protein and high level of p21 protein were associated with a shorter disease-related survival. We did not find p27 protein expression to be useful as a prognostic indicator in vulvar carcinoma patients. (C) 2004 Elsevier Inc. All rights reserved.