Liang J T, Chang K J, Chen J C, Lee C C, Cheng Y M, Hsu H C, Chien C T, Wang S M
Department of Surgery, National Taiwan University Hospital, Taipei.
Hepatogastroenterology. 1999 Mar-Apr;46(26):883-90.
BACKGROUND/AIMS: DNA replication error (RER) was found to play a role in the carcinogenesis of a subset of sporadic colorectal cancers. This study was conducted to evaluate the clinicopathologic implications of RER in T3N0M0 stage colorectal cancers. To better understand the carcinogenesis of sporadic colorectal cancer, the RER status was further correlated with the alterations of K-ras, p53 and deleted in colorectal cancer (DCC) genes which were frequently involved in the adenoma-carcinoma sequence.
Seventy-eight patients with curatively resected T3N0M0 stage sporadic colorectal cancer were accumulated. The stored frozen tissues were retrieved for analyses of 1) microsatellite instability at 7 distinct chromosomal loci, 2) loss of heterozygosity at DCC gene, 3) K-ras gene mutation, 4) p53 expression, and 5) DNA content. The RER status was correlated with various clinicopathologic and molecular genetic factors. The survival of patients stratified by RER status was analyzed by Kaplan-Meier estimator.
The RER-positive tumor was detected in 32.1% (25/78) of patients. The RER-positive cancer patients presented with distinct clinicopathologic features including young age of tumor onset, proximal tumor location, mucin production in histology, a higher rate of synchronous and metachronous colorectal cancers, and an increased incidence of extracolonic primary cancer. Patients with RER-positive tumor were found to have an improved prognosis with the 5-year survival probability of 76% and 45% in RER-positive and RER-negative groups, respectively (p < 0.05). The RER-positive tumors tended to have normal p53 expression, DNA diploidy, and a lower DNA index. The rate for the loss of heterozygosity of DCC gene was significantly lower in RER-positive tumors. RER status was not associated with K-ras mutation.
The clinicopathologic features and carcinogenesis of RER-positive sporadic colorectal cancers were considered different from those of RER-negative tumors. The presence of RER may identify a subset of less aggressive tumors with good prognosis in T3N0M0 stage colorectal cancers.
背景/目的：DNA复制错误（RER）被发现参与了一部分散发性结直肠癌的致癌过程。本研究旨在评估RER在T3N0M0期结直肠癌中的临床病理意义。为了更好地理解散发性结直肠癌的致癌机制，进一步将RER状态与K-ras、p53和结直肠癌缺失基因（DCC）的改变相关联，这些基因常参与腺瘤-癌序列。
收集78例接受根治性切除的T3N0M0期散发性结直肠癌患者。取出储存的冷冻组织进行以下分析：1）7个不同染色体位点的微卫星不稳定性；2）DCC基因杂合性缺失；3）K-ras基因突变；4）p53表达；5）DNA含量。将RER状态与各种临床病理和分子遗传因素相关联。采用Kaplan-Meier估计法分析按RER状态分层的患者生存率。
32.1%（25/78）的患者检测到RER阳性肿瘤。RER阳性的癌症患者具有独特的临床病理特征，包括肿瘤发病年龄轻、肿瘤位于近端、组织学上有黏液产生、同时性和异时性结直肠癌发生率较高以及结肠外原发性癌发生率增加。RER阳性肿瘤患者的预后较好，RER阳性组和RER阴性组的5年生存率分别为76%和45%（p<0.05）。RER阳性肿瘤倾向于具有正常的p53表达、DNA二倍体和较低的DNA指数。RER阳性肿瘤中DCC基因杂合性缺失率显著较低。RER状态与K-ras突变无关。
RER阳性散发性结直肠癌的临床病理特征和致癌机制被认为与RER阴性肿瘤不同。RER的存在可能在T3N0M0期结直肠癌中识别出一部分侵袭性较小、预后良好的肿瘤。
