非小细胞肺癌中凋亡指数的临床意义：与p53、mdm2、pRb和p21WAF1/CIP1蛋白表达的相关性

Clinical significance of apoptotic index in non-small cell lung cancer: correlation with p53, mdm2, pRb and p21WAF1/CIP1 protein expression.

作者信息

Dworakowska D, Jassem E, Jassem J, Karmoliński A, Dworakowski R, Wirth T, Gruchała M, Rynkiewicz A, Skokowski J, Yla-Herttuala S, Jaśkiewicz K, Czestochowska E

机构信息

Department of Internal Medicine, Endocrinology and Haemostatic Disorders, Medical University of Gdańsk, Gdańsk, Poland.

出版信息

J Cancer Res Clin Oncol. 2005 Sep;131(9):617-23. doi: 10.1007/s00432-005-0010-7. Epub 2005 Oct 20.

DOI:10.1007/s00432-005-0010-7

PMID:16028106

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12161267/

Abstract

PURPOSE

The aim of this study was to assess the prognostic relevance of apoptotic index (AI), considered alone or together with expression of several proteins controlling G1 check point (p53, mdm2, pRb and p21WAF1/CIP1) in non-small cell lung cancer (NSCLC) patients.

METHODS

Study group included 50 NSCLC patients who underwent curative pulmonary resection. Apoptosis was detected with the use of TUNEL technique and AI was defined as the number of apoptotic cells per 1,000 tumor cells. The expression of p53, mdm2, pRb and p21WAF1/CIP1 was assessed immunohistochemically.

RESULTS

The mean and median AI calculated for all 50 patients was 14 and 9, respectively. Patients with lower (<14) and higher (> or =14) AI constituted 35 (70%) and 15 (30%) of cases, respectively. AI was not correlated with patient clinical characteristics, and expression of p53, pRb and p21WAF1/CIP1 . However, lower AI was correlated with over-expression of mdm2 protein (P=0.04). Median survival for patients with lower and higher AI was 43 months and 22 months, respectively, and 5-year survival probability-60 and 25%, respectively (P=0.03). In multivariate analysis, the only variable associated with shortened survival was AI (P=0.03, HR=2.9, 95% CI 1.95-3.86).

CONCLUSIONS

These results suggest that AI correlates with mdm2 protein expression and influences survival in NSCLC.

摘要

目的

本研究旨在评估凋亡指数（AI）单独或与几种控制G1期检查点的蛋白（p53、mdm2、pRb和p21WAF1/CIP1）的表达共同在非小细胞肺癌（NSCLC）患者中的预后相关性。

方法

研究组包括50例行根治性肺切除术的NSCLC患者。采用TUNEL技术检测凋亡情况，AI定义为每1000个肿瘤细胞中凋亡细胞的数量。采用免疫组织化学方法评估p53、mdm2、pRb和p21WAF1/CIP1的表达。

结果

50例患者的AI均值和中位数分别为14和9。AI较低（<14）和较高（≥14）的患者分别占35例（70%）和15例（30%）。AI与患者的临床特征以及p53、pRb和p21WAF1/CIP1的表达均无相关性。然而，较低的AI与mdm2蛋白的过表达相关（P=0.04）。AI较低和较高的患者中位生存期分别为43个月和22个月，5年生存概率分别为60%和25%（P=0.03）。多因素分析显示，与生存期缩短相关的唯一变量是AI（P=0.03，HR=2.9，95%CI 1.95-3.86）。