Xu Wei, Cheng Yong, Shen Xiong-Fei
Department of Gastrointestinal Surgery, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2012 Nov;43(6):821-6.
To investigate the incidence of P53 and K-ras gene mutation in colorectal adenomas and primary colorectal carcinomas.
There were 25 normal samples, 38 samples of colorectal adenoma, 78 samples of single primary colorectal cancer and 19 samples of multiple primary colorectal carcinomas (7 synchronous colorectal carcinomas and 12 metachronous colorectal carcinomas) collected in this study. With the analysis of clinico-pathologic features for each patient, exon 5-8 of P53 gene and codon 12-13 of K-ras gene of each sample were extended by real-time PCR. Multi-factor correlation analysis was carried out between the clinicopathologic features and the mutation of P53 and K-ras gene in colorectal adenoma and primary colorectal cancer.
The P53 gene mutation is 0% (0/25),44.8%(17/38), 43.6% (34/78) and 42.1% (8/19) respectively in normal mucosa tissue, colorectal adenomas, single lesion and multiple lesion of primary colorectal carcinomas, while the proportion of K-ras gene mutation was 0% (0/25), 18.4%(7/38), 39.7% (31/78), 47.4% (9/19) respectively. In our investigation there were obvious statistical differences as to the proportion of mutation of the P53 and K-ras gene between normal mucosa tissue and other three groups respectively (P<0.05), while statistical differences as to the proportion of mutation of K-ras gene were found between colorectal adenomas group and single or multiple colorectal carcinoma group (P<0.05). There was significant statistical difference between P53 and K-ras gene mutation in colorectal adenomas (P<0.05). In addition, there were no statistical differences as to the proportion of mutation of the P53 and K-ras gene between the stage I , II and well-differentiated ones of primary colorectal cancers and the stageIII IV and poorly-differentiated ones. There was no relationship between the age, gender, family history and tumor locations of the patients and the mutation of the P53 and K-ras gene. The stage and grade of differentiation of cancer was not the risky factor of the mutation of the P53 and K-ras gene in primary colorectal cancers.
The cancers.
results of this study not only suggest that mutation of P53 suppressor gene and K-ras play a significant role in the procedure of colorectal tumorigenesis, but also indicate that the mutation of P53 gene occurs earlier than K-ras mutation does during tumorigenesis.
探讨P53和K-ras基因突变在大肠腺瘤及原发性结直肠癌中的发生率。
本研究收集了25份正常样本、38份大肠腺瘤样本、78份单发原发性结直肠癌样本以及19份多发原发性结直肠癌样本（7份同时性结直肠癌和12份异时性结直肠癌）。对每位患者的临床病理特征进行分析，通过实时荧光定量PCR扩增各样本P53基因的第5-8外显子和K-ras基因的第12-13密码子。对大肠腺瘤和原发性结直肠癌的临床病理特征与P53和K-ras基因突变进行多因素相关性分析。
P53基因突变在正常黏膜组织、大肠腺瘤、单发原发性结直肠癌和多发原发性结直肠癌中的发生率分别为0%（0/25）、44.8%（17/38）、43.6%（34/78）和42.1%（8/19），而K-ras基因突变率分别为0%（0/25）、18.4%（7/38）、39.7%（31/78）、47.4%（9/19）。本研究中，正常黏膜组织与其他三组之间P53和K-ras基因突变率差异均有统计学意义（P<0.05），而大肠腺瘤组与单发或多发结直肠癌组之间K-ras基因突变率差异有统计学意义（P<0.05）。大肠腺瘤中P53和K-ras基因突变有显著统计学差异（P<0.05）。此外，原发性结直肠癌的Ⅰ、Ⅱ期及高分化者与Ⅲ、Ⅳ期及低分化者之间P53和K-ras基因突变率无统计学差异。患者的年龄、性别、家族史及肿瘤部位与P53和K-ras基因突变无关。癌症的分期及分化程度不是原发性结直肠癌中P53和K-ras基因突变的危险因素。
本研究结果不仅提示P53抑癌基因和K-ras基因的突变在结直肠癌发生过程中起重要作用，而且表明在肿瘤发生过程中P53基因突变早于K-ras基因突变。
