Odze Robert D, Brien Tom, Brown Charlotte A, Hartman Christopher J, Wellman Axel, Fogt Franz
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Am J Gastroenterol. 2002 May;97(5):1235-42. doi: 10.1111/j.1572-0241.2002.05696.x.
There is growing interest in the biological and molecular features and neoplastic potential of colonic hyperplastic polyps because of the recent finding of K-ras mutations in many of these lesions. Hyperplastic polyps may also develop in chronic ulcerative colitis (CUC), but it is unclear if these are biologically similar to the sporadic type. The aim of this study was to evaluate and compare the molecular profile of CUC-associated hyperplastic polyps with sporadic hyperplastic polyps of the colon.
Thirty-nine hyperplastic polyps from 26 CUC patients, 39 sporadic hyperplastic polyps from 29 age- and sex-matched patients without CUC, and 26 colonic mucosal biopsies from 22 patients with CUC but without hyperplastic polyps were analyzed by polymerase chain reaction for loss of heterozygosity of APC, 3p, p53, and p16 and for mutations in codons 12, 13, and 61 of the K-ras gene. Immunohistochemical evaluations for the proliferation-associated nuclear peptide Ki67 (MIB-1) and p27 were also performed on a subset of hyperplastic polyps.
CUC-associated hyperplastic polyps showed a proportion of genetic alterations (47%) similar to that of sporadic hyperplastic polyps (33%) (p > 0.05), and neither significantly differed from chronically inflamed mucosae in CUC patients without hyperplastic polyps. Furthermore, in a small group of CUC patients in which informative tissue was available from both their hyperplastic polyps and adjacent flat colitic mucosae, the polyps contained mutations that were not present in the underlying mucosa. Loss of heterozygosity of APC, 3p, p53, p16, and K-ras mutations were present in 21%, 40%, 27%, 20%, and 19% of CUC patients with hyperplastic polyps, respectively, and in 0%, 11%, 20%, 13%, and 13% of non-CUC patients with sporadic polyps, respectively. Both CUC-associated and sporadic hyperplastic polyps showed a substantial number of cases (46% and 64% of cases, respectively) with loss of p27 expression, and both types of lesions showed similar MIB-1 proliferation indices.
These data suggest that CUC-associated hyperplastic polyps are genotypically similar to the sporadic type. This study adds to the expanding list of molecular alterations that have been discovered in hyperplastic polyps, and lends further support to the controversial theory that these lesions may have neoplastic potential.
由于最近在许多此类病变中发现K-ras基因突变，人们对结肠增生性息肉的生物学和分子特征以及肿瘤发生潜能的兴趣日益增加。增生性息肉也可在慢性溃疡性结肠炎（CUC）中发生，但尚不清楚这些息肉在生物学上是否与散发性息肉相似。本研究的目的是评估和比较CUC相关增生性息肉与结肠散发性增生性息肉的分子特征。
对26例CUC患者的39个增生性息肉、29例年龄和性别匹配的非CUC患者的39个散发性增生性息肉以及22例有CUC但无增生性息肉患者的26份结肠黏膜活检组织进行聚合酶链反应分析，检测APC、3p、p53和p16的杂合性缺失以及K-ras基因第12、13和61密码子的突变。还对一部分增生性息肉进行了增殖相关核肽Ki67（MIB-1）和p27的免疫组化评估。
CUC相关增生性息肉显示出与散发性增生性息肉相似的基因改变比例（47%对33%）（p>0.05），且与无增生性息肉的CUC患者的慢性炎症黏膜均无显著差异。此外，在一小部分CUC患者中，增生性息肉及其相邻的扁平结肠炎黏膜均有可供分析的组织，息肉中存在其下方黏膜中未出现的突变。APC、3p、p53、p16杂合性缺失以及K-ras突变分别在21%、40%、27%、20%和19%的有增生性息肉的CUC患者中出现，在无CUC的散发性息肉患者中分别为0%、11%、20%、13%和13%。CUC相关和散发性增生性息肉均有相当数量的病例（分别为46%和64%）出现p27表达缺失，且两种病变的MIB-1增殖指数相似。
这些数据表明，CUC相关增生性息肉在基因型上与散发性息肉相似。本研究增加了在增生性息肉中发现的分子改变的种类，并进一步支持了这些病变可能具有肿瘤发生潜能这一有争议的理论。
