Prognostic value of proliferation, apoptosis, defective DNA mismatch repair, and p53 overexpression in patients with resected dukes' B2 or C colon cancer: A North Central Cancer Treatment Group study
Prognostic value of proliferation, apoptosis, defective DNA mismatch repair, and p53 overexpression in patients with resected dukes' B2 or C colon cancer: A North Central Cancer Treatment Group study
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DOI：
10.1200/jco.2004.10.042
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发表时间：
2004-05-01
影响因子：
45.3
通讯作者：
Witzig, TE
中科院分区：
文献类型：
--
作者：
Garrity, MM;Burgart, LJ;Witzig, TE
目的结肠癌的分子生物学研究为阐明其发病机制提供了新的思路，但其重要性尚不清楚。标志物在预测预后中的作用。本研究探讨了TUNEL，bcl-2，p53，增殖标记Ki-67和DNA错配修复（MMR）状态与Dukes'B2和C期结直肠adenocarcinoma.Patients和方法肿瘤组织从366例（75%Dukes' C，25%Dukes ' 132）从四个随机北中央癌症治疗组III期手术辅助试验的预后意义。81%的患者接受了辅助治疗，主要是氟尿嘧啶（FU）（90%）。肿瘤位置主要为结肠（87%）。采用免疫组化法检测TUNEL法、Ki-67、p53、bcl-2和MMR。探讨肿瘤分期、分级、MMR、Ki-67和流式细胞术标记物（倍体和S期）之间的相互关系以及与总生存期（CS）和无病生存期（DFS）的关系。结果单因素分析显示，B2期、低分级、二倍体、Ki-67> 27%、p53正常和FU为基础的辅助治疗与OS和DFS的改善显著相关（P < 0.05）。
Purpose Molecular studies of colon cancer have provided insights into pathogenesis, yet it is unclear how important these. markers are in predicting prognosis. This study investigated the prognostic significance of TUNEL, bcl-2, p53, proliferation marker Ki-67 and DNA mismatch repair (MMR) status in patients with Dukes' stage B2 and C colorectal adenocarcinomas.Patients and Methods Tumor tissue from 366 patients (75% Dukes' C, 25% Dukes' 132) from four randomized North Central Cancer Treatment Group phase III surgical adjuvant trials were used. Eighty-one percent of patients received adjuvant treatment, which was primarily fluorouracil (FU) based (90%). Tumor location was predominantly (87%) the colon. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), Ki-67, p53, bcl-2, and MMR were assayed using immunohistochemistry. Stage, grade, MMR, Ki-67, and previously determined flow cytometry markers (ploidy and S phase) were explored for associations with each other and with overall survival (CS) and disease-free survival (DFS).Results Univariately, stage B2, low grade, diploid, Ki-67 more than 27%, normal p53, and FU-based adjuvant treatment were significantly associated with improved OS and DFS (P