Xu H J, Quinlan D C, Davidson A G, Hu S X, Summers C L, Li J, Benedict W F
Center for Biotechnology, Baylor College of Medicine, The Woodlands, Tex. 77381.
J Natl Cancer Inst. 1994 May 4;86(9):695-9. doi: 10.1093/jnci/86.9.695.
Altered retinoblastoma (RB [also known as RB1]) gene expression was initially found in a small cohort study to occur in five (22%) of 23 patients with primary stage I and II non-small-cell lung carcinomas (NSCLCs). Putative mutation of the p53 gene (also known as TP53) has also been found to occur frequently in stage I and II NSCLCs and to be associated with more aggressive disease and a poorer prognosis.
Our purpose was to determine the Rb protein status in the same cohort that had been previously studied for their p53 protein status and to document whether loss of Rb protein expression was also an important factor in overall survival.
One hundred one stage I or II NSCLC specimens were analyzed by immunohistochemical staining. These paraffin-embedded tumor sections were obtained from individual paraffin blocks prepared for each patient in the previous study. Patient survival status was obtained from hospital and tumor registry records.
Altered Rb protein expression was found in 24 of 101 stage I and II NSCLCs. The median survival was 32 months for patients with Rb-positive (Rb+) tumors and 18 months for individuals in whom expression of Rb protein was absent or altered (Rb-) in tumor cells. Log-rank analysis of the differences in overall survival was statistically significant (P = .007). When these results were combined with the p53 status in the same tumor, the median survival was 12 months for those individuals who had theoretically the worst pattern (Rb-/p53+) and 46 months for those patients with theoretically the best pattern (Rb+/p53-) (P < .001). The Rb+ and Rb- groups in this cohort were well balanced with respect to the distribution of age, disease stage, histologic types, p53 status, and sex. Using a multivariate proportional hazards regression model, both altered Rb and p53 status were found to be significantly associated with poor prognosis (P = .005 and .012, respectively) in the overall cohort.
Altered Rb protein expression is an independent prognostic marker for overall decreased survival in early-stage NSCLC as detected by absence of nuclear Rb protein staining. There appears to be a poorer prognosis when loss of Rb protein function and mutated p53 protein occur in the same tumor.
If these findings can be confirmed in larger prospective studies, the results would suggest that both the Rb and p53 status should be utilized as independent prognostic factors in early-stage NSCLC.
在一项小型队列研究中，最初发现23例Ⅰ期和Ⅱ期原发性非小细胞肺癌（NSCLC）患者中有5例（22%）的视网膜母细胞瘤（RB [也称为RB1]）基因表达发生改变。p53基因（也称为TP53）的推定突变在Ⅰ期和Ⅱ期NSCLC中也经常出现，并与更具侵袭性的疾病和更差的预后相关。
我们的目的是确定在先前已研究过p53蛋白状态的同一队列中的Rb蛋白状态，并记录Rb蛋白表达缺失是否也是总生存期的一个重要因素。
通过免疫组织化学染色分析101例Ⅰ期或Ⅱ期NSCLC标本。这些石蜡包埋的肿瘤切片取自先前研究中为每位患者制备的单个石蜡块。患者生存状态来自医院和肿瘤登记记录。
在101例Ⅰ期和Ⅱ期NSCLC中，有24例Rb蛋白表达发生改变。Rb阳性（Rb+）肿瘤患者的中位生存期为32个月，肿瘤细胞中Rb蛋白表达缺失或改变（Rb-）的个体中位生存期为18个月。总生存期差异的对数秩分析具有统计学意义（P = 0.007）。当将这些结果与同一肿瘤中的p53状态相结合时，理论上模式最差（Rb-/p53+）的个体中位生存期为12个月，理论上模式最佳（Rb+/p53-）的患者中位生存期为46个月（P < 0.001）。该队列中的Rb+组和Rb-组在年龄、疾病分期、组织学类型、p53状态和性别分布方面平衡良好。使用多变量比例风险回归模型，在整个队列中发现Rb和p53状态改变均与不良预后显著相关（分别为P = 0.005和0.012）。
通过核Rb蛋白染色缺失检测到的Rb蛋白表达改变是早期NSCLC总生存期降低的独立预后标志物。当同一肿瘤中发生Rb蛋白功能丧失和p53蛋白突变时，预后似乎更差。
如果这些发现能够在更大规模的前瞻性研究中得到证实，结果将表明Rb和p53状态都应作为早期NSCLC的独立预后因素。
