Genetic analysis in dysplasia and carcinoma accompanied with longstanding ulcerative colitis

Vogelstein等1. 1988年提出了大肠癌的多步致癌模型，许多研究机构已经注意到与大肠癌相关的许多遗传异常。另一方面，随着溃疡性结肠炎（UC）患者的长期增加，已经研究了伴有UC并发症的结直肠癌中K-ras和p53基因的突变，尽管这个问题现在仍有争议。我们研究了癌症合并长期溃疡性结肠炎中ras基因突变、p53蛋白过度表达和密码子201的DCC多态性，以阐明异型增生的诊断，发现在难以判断是否再生的结肠炎异型增生中，如果合并癌症，p53免疫染色阳性率很高，但在DCC和ras异常中，未检测到发育异常和再生上皮之间的差异。ras基因突变率极低，提示尽管DCC基因多态性和ras基因点突变的检测对长期溃疡性结肠炎伴异型增生的诊断意义不大，但监测结肠镜检查中p53阳性的患者很可能有癌症并发症。

Vogelstein et a1. proposed a multistep carcinogenesis model of colorectal cancer in 1988, and a number of genetic abnormalities associated with colorectal cancer have been noted in many institutes. On the other hand, with the increase in patients contracting ulcerative colitis (UC) for a long period, mutation of the K-ras and p53 genes in colorectal cancer with a complication of UC,has been investigated, although this issue now will be controversial. we investigated the ras gene mutations, overexpression of p53 protein and DCC polymorphism in codon 201 in cancer complicated with longstanding ulcerative colitis to elucidate the diagnosis of dysplasia and found that in dysplasia of colitis which are difficult to judge whether to be regenerative, p53 immunostaining was positive at a high rate if complicated with cancer but in DCC and ras abnormalities, no differences between dysplasia and regenerative epithelia were detected. Mutaions of ras gene were extremely low.In conclusion, our studies suggested that p53 positive patients found in surveillance colonoscopy are likely to have complication of cancer although the detection of DCC polymorphism and point mutation of ras genes was not useful for the diagnosis of dysplasia accompanied with longstanding ulcerative colitis.