Usefulness of analysis of p53 alteration and observation of surface microstructure for diagnosis of ulcerative colitis-associated colorectal neoplasia.
Usefulness of analysis of p53 alteration and observation of surface microstructure for diagnosis of ulcerative colitis-associated colorectal neoplasia.
复制标题
分析 p53 改变和观察表面微观结构对于诊断溃疡性结肠炎相关结直肠肿瘤的有用性。
DOI：
--
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
T. Chiba
中科院分区：
文献类型：
--
作者：
S. Fujii;T. Fujimori;T. Chiba
溃疡性结肠炎（UC）患者的结直肠癌发病率较高。UC相关的结直肠癌被认为发生在既存UC相关异型增生的患者中。对长期UC患者进行UC相关异型增生和早期癌症的诊断对于治疗UC相关肿瘤至关重要。然而，很难通过内窥镜检测到UC相关的异型增生和早期癌症，也很难从病理学上区分这些肿瘤和炎性再生上皮。本研究的目的是澄清表面微观结构的观察是否可以帮助检测UC相关的neopalsia，以及遗传改变的分析是否可以用于区分UC相关的瘤形成和炎症再生上皮。组织样本来自8例UC相关肿瘤的结肠切除术标本。我们用体视显微镜检查了这些组织的表面显微结构。我们还调查了K-ras基因第12位密码子的突变，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和改变的p53基因，采用免疫组化和PCR-SSCP。UC相关瘤变的表面显微结构显示椭圆形和/或棒状和/或树枝状凹陷的密集分布以及绒毛外观。59.5%的UC相关肿瘤细胞核内有p53蛋白积聚。在95.2%的UC相关肿瘤中检测到p53外显子5-8的突变，并且在92.9%的UC相关肿瘤中检测到这些突变，这些肿瘤显示p53免疫组化染色阴性。再生上皮中p53外显子5-8的突变很少发生。K-ras基因突变率为7.4%。总之，p53的免疫组化和PCR-SSCP分析将是有用的工具，UC相关的肿瘤和炎症再生上皮之间的病理区分，和表面微观结构的观察可能有助于准确的内镜检测UC相关的肿瘤。
Patients with ulcerative colitis (UC) have a higher incidence of colorectal cancer. UC-associated colorectal cancer is thought to develop in patients with preexisting UC-associated dysplasia. It is crucial to diagnose UC-associated dysplasia and early stage of cancer in patients with long-standing UC for the purpose of treatment of UC-associated neoplasia. However, it is difficult to detect UC-associated dysplasia and the early stage of cancer endoscopically, and to discriminate these neoplasias from inflammatory regenerative epithelium pathologically. The aim of this study was to clarify whether observation of the surface microstructure could aid in the detection of UC-associated neopalsia, and whether analysis of genetic alterations could be used to discriminate between UC-associated neoplasia and inflammatory regenerative epithelium. Tissue samples were obtained from colectomy specimens from eight cases of UC-associated neoplasia. We examined the surface microstructure of these tissues using stereomicroscopy. We also investigated mutation of K-ras codon 12 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and alteration of the p53 gene, using immunohistochemistry and PCR-single stranded conformation polymorphism (PCR-SSCP). The surface microstructure of UC-associated neoplasia revealed a packed distribution of oval and/or, club-shaped and/or, branch-shaped pits and a villous appearance. Nuclear accumulation of p53 protein occurred in 59.5% of UC-associated neoplasia. Mutations of the p53 exon 5-8 were detected in 95.2% of UC-associated neoplasia, and these mutations were detected in 92.9% of UC-associated neoplasia that showed negative p53 immunohistochemical staining. Mutations of the p53 exon 5-8 in regenerative epithelium occurred infrequently. The K-ras mutation rate in UC-associated neoplasia was 7.4%. In conclusion, immunohistochemistry and PCR-SSCP analysis of p53 would be useful tools for pathological discrimination between UC-associated neoplasia and inflammatory regenerative epithelium, and observation of the surface microstructure may contribute to accurate endoscopic detection of UC-associated neoplasia.