Nishio M, Koshikawa T, Yatabe Y, Kuroishi T, Suyama M, Nagatake M, Sugiura T, Ariyoshi Y, Mitsudomi T, Takahashi T
Departments of Internal Medicine, Aichi Cancer Center Hospital, Nagoya 464, Japan.
Clin Cancer Res. 1997 Jul;3(7):1051-8.
This study was conducted to evaluate the prognostic significance of cyclin D1 and retinoblastoma (Rb) expression in combination with abnormal p53 accumulation in primary, resected non-small cell lung cancers (NSCLCs). We evaluated immunohistochemically the expression of cyclin D1 and Rb in 208 NSCLC patients whose resections were consecutively performed between January 1984 and December 1988 and determined their prognostic significance by comparison with follow-up data. Expression of cyclin D1 and Rb was detected immunohistochemically in 39 and 80% of the 208 NSCLCs, respectively. The Kaplan-Meier survival curve demonstrated that absence of cyclin D1 expression was significantly associated with shortened survival (P = 0.01 by the log-rank test), particularly in adenocarcinomas (n = 100; P = 0.004). Expression status of the Rb protein was not significantly associated with clinical outcome in any of the cohorts. The predictive power of these prognosticators was also assessed in combination with findings for abnormal p53 accumulation by multivariate analysis using the Cox proportional hazards modeling. Patients with cyclin D1-negative tumors had a significantly greater risk of earlier death than those with cyclin D1-positive tumors (risk ratio, 1.61; P = 0.03), particularly in adenocarcinomas (risk ratio, 2.49; P = 0.002). Cases showing abnormal p53 accumulation tended to have a shortened survival only when the tumors were adenocarcinomas (risk ratio, 1.75; P = 0.06). Absence of cyclin D1 expression may be a useful prognosticator for shortened survival in primary, resected NSCLCs with particular significance for adenocarcinomas. In contrast, Rb expression status is not a useful prognostic factor for any type of NSCLC.
本研究旨在评估细胞周期蛋白D1和视网膜母细胞瘤（Rb）表达联合p53异常积聚在原发性、已切除非小细胞肺癌（NSCLC）中的预后意义。我们对1984年1月至1988年12月期间连续进行手术切除的208例NSCLC患者进行免疫组织化学评估，检测细胞周期蛋白D1和Rb的表达，并通过与随访数据比较确定其预后意义。在208例NSCLC中，分别有39%和80%通过免疫组织化学检测到细胞周期蛋白D1和Rb的表达。Kaplan-Meier生存曲线显示，细胞周期蛋白D1表达缺失与生存期缩短显著相关（对数秩检验P = 0.01），尤其是在腺癌中（n = 100；P = 0.004）。Rb蛋白的表达状态在任何队列中均与临床结局无显著相关性。还通过使用Cox比例风险模型进行多变量分析，结合p53异常积聚的结果评估了这些预后指标的预测能力。细胞周期蛋白D1阴性肿瘤患者比细胞周期蛋白D1阳性肿瘤患者更早死亡的风险显著更高（风险比，1.61；P = 0.03），尤其是在腺癌中（风险比，2.49；P = 0.002）。仅当肿瘤为腺癌时，显示p53异常积聚的病例生存期往往缩短（风险比，1.75；P = 0.06）。细胞周期蛋白D1表达缺失可能是原发性、已切除NSCLC生存期缩短的有用预后指标，对腺癌尤为重要。相比之下，Rb表达状态对任何类型的NSCLC都不是有用的预后因素。
