Kim H J, Chang S K
Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea.
Korean J Intern Med. 1998 Jul;13(2):110-6. doi: 10.3904/kjim.1998.13.2.110.
Long standing ulcerative colitis (UC) has been known to be one of the precancerous diseases of colorectal cancer. Although the frequent loss of p53 allele (LOH) and aneuploidy were reported as the molecular events in carcinoma and dysplasia known as the precursor of UC, p53 genetic alteration was not reported in indefinite dysplasia and UC involved mucosa in long standing UC. Therefore, we investigated the mutational inactivation of the p53 gene in UC patients who showed dysplastic mucosa, as well as non-dysplastic mucosa on H & E stain and, secondly, if there is p53 mutation, we examined the relationship between p53 alteration and clinical data.
Sixteen patients with UC who had different duration of colitis were studied by endoscopic examination with rectal mucosal biopsies, p53 gene alterations were detected by PCR-SSCP for exon 4-8 and immunohistochemical staining with p53 monoclonal antibody.
Among 16 patients, 2 patients (12%) showed dysplasia on H-E stain. The p53 point mutations were detected in 4 (two dysplasia and 2 normal looking mucosa) on PCR-SSCP. 4 patients who had p53 gene mutation were positive in immunohistochemical staining. With regard to clinical characteristics, these patients with p53 point mutation showed poor response to medical treatment.
These results suggest that the p53 mutation may be an early molecular event of cancerous change in UC.
长期溃疡性结肠炎（UC）一直被认为是结直肠癌的癌前疾病之一。尽管p53等位基因缺失（LOH）和非整倍体在UC的癌前病变即癌和发育异常中被报道为分子事件，但在长期UC的不确定发育异常和UC累及的黏膜中未报道p53基因改变。因此，我们研究了在苏木精和伊红（H&E）染色显示发育异常黏膜以及非发育异常黏膜的UC患者中p53基因的突变失活情况，其次，如果存在p53突变，我们检查了p53改变与临床数据之间的关系。
对16例患有不同病程结肠炎的UC患者进行内镜检查并取直肠黏膜活检，通过聚合酶链反应-单链构象多态性（PCR-SSCP）检测外显子4-8的p53基因改变，并用p53单克隆抗体进行免疫组织化学染色。
16例患者中，2例（12%）在H-E染色中显示发育异常。通过PCR-SSCP在4例患者（2例发育异常和2例外观正常的黏膜）中检测到p53点突变。4例有p53基因突变的患者免疫组织化学染色呈阳性。关于临床特征，这些有p53点突变的患者对药物治疗反应较差。
这些结果表明p53突变可能是UC癌变的早期分子事件。
