Akkiprik Mustafa, Ataizi-Celikel Cigdem, Düşünceli Fikret, Sönmez Ozgür, Gulluoglu Bahadir M, Sav Aydin, Ozer Ayşe
Marmara University, School of Medicine, Department of Medical Biology, Tibbyie C. no. 49, 34668 Haydarpasa, Istanbul, Turkey.
J Gastrointestin Liver Dis. 2007 Mar;16(1):11-7.
Genetic alterations of p53, K-ras and DCC genes have a pivotal role in the colorectal cancer progression. The aim of this study was to clarify the association between K-ras mutations, p53 aberrations and DCC loss of heterozygosity (LOH), with the patient outcome and tumor characteristics in 43 stage I-II colorectal cancer patients.
Mutations in exons 5-8 of the p53 gene and codon 12 and/or 13 of the K-ras gene were assayed by PCR-SSCP and then confirmed by DNA sequencing. DCC LOH was studied by PCR-RFLP, while p53 immunohistochemistry was also made.
Mutations of the p53 gene were found in 14 (32.5%) tumors. Five (12%) cases showed mutation of the K-ras gene. Nuclear staining of p53 was found in 22 (51 %) cases. DCC LOH was found in 5 (12%) cases. Cases with guanine to thymine substitution that occurred in K-ras codon 12 and DCC LOH were found to be more aggressive than other cases with codon 12 mutations or DCC wild-type phenotype. Many tumors with p53 over-expression were localized on the left side of the colon (p=0.005). The stage of the tumor was higher in patients who died during the follow-up period, when compared to the ones who have survived.
Although none of these genetic alterations showed a significant prognostic value, specific mutation of K-ras gene and DCC LOH phenotype might have a predictive prognostic implication in colorectal cancer. Furthermore, different etiopathogenetic mechanisms might be involved in the tumorigenesis of the left and right colon.
p53、K-ras和DCC基因的遗传改变在结直肠癌进展中起关键作用。本研究旨在阐明43例I-II期结直肠癌患者中K-ras突变、p53异常和DCC杂合性缺失（LOH）与患者预后及肿瘤特征之间的关联。
采用PCR-SSCP检测p53基因外显子5-8及K-ras基因密码子12和/或13的突变，然后通过DNA测序进行确认。采用PCR-RFLP研究DCC LOH，同时进行p53免疫组化检测。
14例（32.5%）肿瘤发现p53基因突变。5例（12%）病例显示K-ras基因突变。22例（51%）病例发现p53核染色阳性。5例（12%）病例发现DCC LOH。发现K-ras密码子12发生鸟嘌呤到胸腺嘧啶替代且存在DCC LOH的病例比其他密码子12突变或DCC野生型表型的病例更具侵袭性。许多p53过表达的肿瘤位于结肠左侧（p = 0.005）。与存活患者相比，随访期间死亡患者的肿瘤分期更高。
尽管这些遗传改变均未显示出显著的预后价值，但K-ras基因的特定突变和DCC LOH表型可能对结直肠癌具有预测预后的意义。此外，左右结肠癌的肿瘤发生可能涉及不同的病因发病机制。
