Association of p27Kip1 levels with recurrence and survival in patients with stage C prostate carcinoma
Association of p27Kip1 levels with recurrence and survival in patients with stage C prostate carcinoma
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DOI：
10.1093/jnci/90.12.916
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发表时间：
1998-06-17
期刊：
影响因子：
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通讯作者：
Lieskovosky, G
中科院分区：
文献类型：
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作者：
Cote, RJ;Shi, Y;Lieskovosky, G
背景：很少有生物学决定因素可以预测局限性前列腺癌患者的预后。我们研究了前列腺肿瘤中细胞周期蛋白激酶抑制剂p27（Kip 1）（也称为p27）的细胞水平是否可以用来预测这种疾病的进展。研究方法：通过免疫组化分析96例经根治性前列腺癌切除术治疗的C期前列腺癌患者原发肿瘤的组织切片，评估肿瘤细胞核中p27的水平。根据显示核p27反应性的肿瘤细胞百分比，将肿瘤分为以下三组之一：低（0%-10%）、中等（11%-50%）和高（>50%）。采用Mantel-Haenszel检验、Kaplan-Meier分析和对数秩检验计算细胞核p27水平与肿瘤分级和分期、血清前列腺特异性抗原（PSA）复发（定义为根治性前列腺切除术后发现血清PSA可检测水平[0.4 ngl mt或更高]）、临床明显疾病复发和生存率相关的概率。所有报告的P值均为双侧。结果：正常前列腺的腔细胞和基底细胞在所有组织切片中均显示高水平的核p27免疫反应。53例肿瘤显示p27高反应性，31例显示中等反应性，12例显示低或检测不到反应性。p27水平降低与肿瘤分级相关（P = 0.001），肿瘤p27水平与术前前列腺特异性抗原水平无关（P = .360）或肿瘤亚期（P = .320），然而，p27反应性降低与复发概率增加显著相关（P = 0.001）和生存率下降（P = 0.010），显示高、中、低p27反应性的肿瘤患者的中位无复发间隔分别为13.7年、8.4年，高、中和低p27反应性组患者的中位生存时间分别为14年、13.5年和8.1年。结论：原发肿瘤细胞核p27免疫反应性水平可用于预测局限性前列腺癌患者的复发和生存。
Background: There are few biologic determinants that are prognostic for patients with localized prostate cancer. We examined whether cellular levels of the cyclin-kinase inhibitor p27(Kip1) (also known as p27) in prostate tumors could be used to predict progression of this disease. Methods: Levels of p27 in tumor cell nuclei were assessed by immunohistochemical analysis of tissue sections from the primary tumors of 96 patients with stage C prostate carcinoma who had been treated by radical prostatectomy. Tumors were classified into one of the following three groups on the basis of the percentage of tumor cells showing nuclear p27 reactivity: low (0%-10%), moderate (11%-50%), and high (>50%). The Mantel-Haenszel test, Kaplan-Meier analysis, and the log-rank test were used to calculate the probability that nuclear p27 levels were associated with tumor grade and substage, with a serum prostate-specific antigen (PSA) recurrence (defined as the finding of a detectable level [0.4 ngl mt or greater] of serum PSA following radical prostatectomy), with the recurrence of clinically evident disease, and with survival. All reported P values are two-sided. Results: Luminal cells and basal cells of normal prostate glands showed high levels of nuclear p27 immunoreactivity in all tissue sections examined. Fifty-three tumors showed high p27 reactivity, 31 showed moderate reactivity, and 12 showed low or no detectable reactivity, Decreased levels of p27 were associated with tumor grade (P = .001), Tumor levels of p27 mere not associated with preoperative prostate-specific antigen levels (P = .360) or with tumor substage (P = .320), However, decreased p27 reactivity was significantly associated with an increased probability of recurrence (P =.001) and decreased survival (P = .010), The median recurrence-free interval for patients with tumors showing high, moderate, or low p27 reactivity was 13.7 years, 8.4 years, and 4.7 years, respectively, Median survival times were more than 14 years, more than 13.5 years, and 8.1 years for patients in the high, moderate, and low p27 reactivity groups, respectively. Conclusion: Levels of nuclear p27 immunoreactivity in the primary tumor can be used to predict recurrence and survival among patients with localized prostate cancer.