Burmer G C, Rabinovitch P S, Haggitt R C, Crispin D A, Brentnall T A, Kolli V R, Stevens A C, Rubin C E
Department of Pathology, University of Washington School of Medicine, Seattle.
Gastroenterology. 1992 Nov;103(5):1602-10. doi: 10.1016/0016-5085(92)91184-6.
Neoplastic progression in patients with chronic ulcerative colitis (UC) is characterized by the development of epithelial dysplasia, which is accompanied by genetic abnormalities that can be detected by flow cytometric and molecular biologic methods. Distribution of and correlation between histologic abnormalities, DNA content, and loss of heterozygosity for a p53 allele (p53 LOH) in the colons of nine UC patients were analyzed. Loss of a p53 allele was found in 85% (22/26) of biopsy specimens classified histologically as carcinoma, 63% (25/40) of biopsy specimens with high grade dysplasia, and 33% (7/21) of biopsy specimens with low grade dysplasia. Loss of heterozygosity for p53 was also found in 9% (5/57) of biopsy specimens indefinite for dysplasia and in 1/18 biopsy specimens negative for dysplasia, showing that this genetic change may occur early in the histological progression towards carcinoma. Aneuploid DNA contents were more common than p53 LOH in regions with negative, indefinite or low grade dysplastic histology; moreover, p53 LOH was detected only in aneuploid cells and not in diploid epithelium. Aneuploidy alone was not as specific a marker for the concomitant presence of dysplasia or carcinoma in a biopsy sample as aneuploidy combined with p53 LOH. These findings show that aneuploidy may precede both p53 LOH and epithelial dysplasia. Two UC patients' colons contained geographically separated clones of cells with different aneuploidies that also showed loss of different p53 alleles, suggesting that neoplasia may arise within different populations of cells in separate areas of the same colon.
慢性溃疡性结肠炎（UC）患者的肿瘤进展以上皮发育异常为特征，伴有可通过流式细胞术和分子生物学方法检测到的基因异常。分析了9例UC患者结肠中组织学异常、DNA含量与p53等位基因杂合性缺失（p53 LOH）之间的分布及相关性。在组织学分类为癌的活检标本中，85%（22/26）发现p53等位基因缺失；在高级别发育异常的活检标本中，63%（25/40）发现缺失；在低级别发育异常的活检标本中，33%（7/21）发现缺失。在发育异常不明确的活检标本中，9%（5/57）也发现了p53杂合性缺失，在发育异常阴性的1/18活检标本中也发现了缺失，表明这种基因变化可能在向癌的组织学进展早期就已发生。在组织学表现为阴性、不明确或低级别发育异常的区域，非整倍体DNA含量比p53 LOH更常见；此外，仅在非整倍体细胞中检测到p53 LOH，而在二倍体上皮细胞中未检测到。单独的非整倍体作为活检样本中同时存在发育异常或癌的标志物，不如非整倍体与p53 LOH联合时特异。这些发现表明，非整倍体可能先于p53 LOH和上皮发育异常出现出现。两名UC患者的结肠中含有地理上分离的具有不同非整倍体的细胞克隆，这些克隆也显示出不同p53等位基因的缺失，这表明肿瘤可能在同一结肠不同区域内的不同细胞群体中发生。
