Chaubert P, Benhattar J, Saraga E, Costa J
Institut Universitaire de Pathologie, Lausanne, Switzerland.
Am J Pathol. 1994 Apr;144(4):767-75.
We have analyzed K-ras mutations and p53 alterations in 39 tumor and nontumor samples taken from nine patients with longstanding ulcerative colitis and colorectal carcinoma. Two of nine invasive carcinomas contained a K-ras mutation. By a combination of immunohistochemistry and single-strand conformation polymorphism analysis, p53 alterations were found in three of nine carcinomas. Five of 13 dysplastic lesions harbored a mutated K-ras gene, even in the absence of detectable changes in associated invasive tumors. One single focus of dysplastic mucosa harbored concomitant K-ras and p53 gene alterations. In two patients, a K-ras mutation was detected in epithelial lesions considered to be devoid of malignant potential (villous regeneration, active colitis). Our results indicate that: 1) the prevalence of K-ras and p53 genetic alterations found in ulcerative colitis-associated colonic carcinomas appears to be lower than in sporadic carcinomas; 2) K-ras mutations can be detected in dysplasia, villous regeneration, and active colitis and affect a subpopulation of the cells composing the lesions; 3) diverse genetic alterations can be detected in the same patient and the dysplastic lesions can exhibit a different genotype than the carcinomas; and 4) at least part of active colitis and villous regeneration lesions should be considered as preneoplastic in ulcerative colitis.
我们分析了从9例患有长期溃疡性结肠炎和结肠直肠癌的患者身上获取的39个肿瘤和非肿瘤样本中的K-ras突变和p53改变。9例浸润性癌中有2例含有K-ras突变。通过免疫组织化学和单链构象多态性分析相结合的方法，在9例癌中有3例发现了p53改变。13例发育异常病变中有5例含有突变的K-ras基因，即使在相关浸润性肿瘤中未检测到可察觉的变化。一个发育异常黏膜的单一病灶同时存在K-ras和p53基因改变。在2例患者中，在被认为无恶性潜能的上皮病变（绒毛再生、活动性结肠炎）中检测到K-ras突变。我们的结果表明：1）溃疡性结肠炎相关结肠癌中发现的K-ras和p53基因改变的发生率似乎低于散发性癌；2）K-ras突变可在发育异常、绒毛再生和活动性结肠炎中检测到，并影响构成病变的细胞亚群；3）同一患者可检测到多种基因改变，发育异常病变可表现出与癌不同的基因型；4）在溃疡性结肠炎中，至少部分活动性结肠炎和绒毛再生病变应被视为癌前病变。
