Sgambato A, Migaldi M, Faraglia B, Garagnani L, Romano G, De Gaetani C, Ferrari P, Capelli G, Trentini G P, Cittadini A
Centro di Ricerche Oncologiche Giovanni XXIII-Istituto di Patologia Generale, Catholic University, Rome, Italy.
Cancer Res. 1999 Jul 1;59(13):3245-50.
p27Kip1 is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. We previously reported a deregulated expression of p27Kip1 in a series of human cancer cell lines and in primary breast and colon cancers. Moreover, p27Kip1 has been reported as an important prognostic factor in primary lung, breast, colon, and prostate cancers. In this study, we evaluated the prognostic value of p27Kip1 in a series of 96 superficial (pTa-1) human bladder carcinomas. High (>50% positive cells), moderate (25-50%), and low (<25%) p27Kip1 staining was observed in 39 (41%), 19 (20%), and 38 (39%) of the 96 primary superficial bladder cancers, respectively. No significant association was found between the expression level of p27Kip1 and tumor stage. Decreased p27Kip1 staining correlated with higher tumor grade (P = 0.001). Interestingly, a significant association was observed between increased expression of p27Kip1 and positivity for p53 (>20% positive cells; P < 0.001). A significant correlation was also observed between low expression of p27Kip1 and decreased disease-free survival (P = 0.0003 by log-rank test) and overall survival (P = 0.01 by log-rank test). Furthermore, on multivariate analysis, low p27Kip1 protein expression was an independent predictor of reduced disease-free survival (P = 0.018; relative risk = 1.95) second only to tumor stage. These data indicate that p27Kip1 protein is frequently expressed at low level in poorly differentiated tumors and suggest that this protein might represent a useful prognostic marker for disease recurrence and overall survival in superficial bladder carcinomas.
p27Kip1是细胞周期蛋白依赖性激酶抑制剂Cip1/Kip1家族的成员，是一种潜在的肿瘤抑制基因。我们之前报道了p27Kip1在一系列人类癌细胞系以及原发性乳腺癌和结肠癌中表达失调。此外，p27Kip1已被报道为原发性肺癌、乳腺癌、结肠癌和前列腺癌的重要预后因素。在本研究中，我们评估了p27Kip1在96例浅表性（pTa-1）人类膀胱癌中的预后价值。在96例原发性浅表性膀胱癌中，分别有39例（41%）、19例（20%）和38例（39%）观察到p27Kip1染色为高（>50%阳性细胞）、中（25%-50%）和低（<25%）。未发现p27Kip1的表达水平与肿瘤分期之间存在显著关联。p27Kip1染色降低与更高的肿瘤分级相关（P = 0.001）。有趣的是，观察到p27Kip1表达增加与p53阳性（>20%阳性细胞；P < 0.001）之间存在显著关联。还观察到p27Kip1低表达与无病生存期降低（对数秩检验P = 0.0003）和总生存期降低（对数秩检验P = 0.01）之间存在显著相关性。此外，在多变量分析中，p27Kip1蛋白低表达是无病生存期降低的独立预测因素（P = 0.018；相对风险 = 1.95），仅次于肿瘤分期。这些数据表明，p27Kip1蛋白在低分化肿瘤中经常低水平表达，并提示该蛋白可能是浅表性膀胱癌疾病复发和总生存期的有用预后标志物。
