Sgambato A, Migaldi M, Leocata P, Ventura L, Criscuolo M, Di Giacomo C, Capelli G, Cittadini A, De Gaetani C
Centro di Ricerche Oncologiche, Giovanni XXIII, Institute of General Pathology, Catholic University, Rome, Italy.
Cancer. 2000 Dec 1;89(11):2247-57. doi: 10.1002/1097-0142(20001201)89:11<2247::aid-cncr13>3.0.co;2-5.
p27KiP1 is a cyclin-dependent kinase inhibitor and is a potential tumor suppressor gene. Reduced expression of p27Kip1 is a powerful negative prognostic marker in primary lung, breast, colon, bladder, and prostate carcinomas. In the current study, the prognostic value of p27Kip1 in gastric cancer was evaluated and compared with other histopathologic parameters and p53 expression.
p27Kip1 and p53 protein expression were determined by immunohistochemistry in 96 gastric carcinomas. The tumors were from a low incidence population and were selected for the absence of lymph node involvement.
Reduced expression of p27KiP1 (< or = 50% positive cells) and nuclear p53 accumulation (> 30% positive cells) were observed in 67 (69.8%) and 9 (9%) tumors, respectively, and were not related to either the pT category or tumor histology. Kaplan-Meier analyses revealed a significant impact on survival by p27Kip1 (P = 0.0001 by log rank test), p53 (P < 0.0001) expression, and the pT category (P < 0.0001). On multivariate analysis, reduced p27Kip1 protein expression was the strongest independent predictor of reduced survival (P = 0.005; relative risk = 3.348) out weighing the pT category (P = 0.010; relative risk = 2.257) and p53 overexpression (P = 0.016; relative risk = 2.618).
These data indicated that immunohistochemical detection of p27Kip1 could help to identify gastric carcinoma patients who are at high risk of death, even in the absence of lymph node involvement, and who might benefit from an adjuvant treatment following surgery.
p27KiP1是一种细胞周期蛋白依赖性激酶抑制剂，是一种潜在的肿瘤抑制基因。p27Kip1表达降低是原发性肺癌、乳腺癌、结肠癌、膀胱癌和前列腺癌中有力的不良预后标志物。在本研究中，评估了p27Kip1在胃癌中的预后价值，并与其他组织病理学参数及p53表达进行比较。
采用免疫组织化学法检测96例胃癌中p27Kip1和p53蛋白表达。这些肿瘤来自低发人群，因无淋巴结受累而入选。
分别在67例（69.8%）和9例（9%）肿瘤中观察到p27KiP1表达降低（阳性细胞≤50%）和核p53积聚（阳性细胞>30%），且二者均与pT分类或肿瘤组织学无关。Kaplan-Meier分析显示，p27Kip1（对数秩检验P=0.0001）、p53（P<0.0001）表达及pT分类（P<0.0001）对生存率有显著影响。多因素分析显示，p27Kip1蛋白表达降低是生存率降低的最强独立预测因素（P=0.005；相对危险度=3.348），其影响超过pT分类（P=0.010；相对危险度=2.257）和p53过表达（P=0.016；相对危险度=2.618）。
这些数据表明，即使在无淋巴结受累的情况下，免疫组织化学检测p27Kip1有助于识别死亡风险高的胃癌患者，这些患者可能从术后辅助治疗中获益。
