Tada T, Watanabe T, Kanazawa T, Kazama S, Koketsu S, Nagawa H
Department of Surgical Oncology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Scand J Gastroenterol. 2004 Nov;39(11):1134-40. doi: 10.1080/00365520410007881.
In recent studies a high frequency of microsatellite instability among colorectal cancers in young patients has been reported, but the frequency of microsatellite instability (MSI) and chromosomal instability among colorectal cancers in young patients has not yet been fully elucidated. Only one report showed an increased loss of heterozygosity (LOH) ratio at 9p locus, which harbors tumor suppressor genes p16. The LOH and MSI status among colorectal cancers in young patients was examined.
Twenty-five patients under 40 years of age diagnosed with colorectal cancer were examined for MSI and LOH using 17 microsatellite markers, and also p16 expression patterns were evaluated by immunohistochemistry and methylation status of the p16 gene was assessed by methylation-specific PCR.
MSI was observed in only one case (4%). LOH at 2p, 5q, 9p, 11q, 17p, and 18q was observed in 41%, 59%, 42%, 35%, 46%, and 56% of cases, respectively. Eighty-three percent of patients showed p16-positive expression patterns. Fifty percent of colorectal cancers in young patients exhibited p16 methylation (3/6).
Our study demonstrated that colorectal cancers in young patients without MSI showed a high frequency of LOH at the 9p locus. However, LOH status at 9p and p16 expression pattern did not show a significant correlation. Other tumor suppressor genes on the 9p, with the exception of p16, may play an important role in the carcinogenesis of colorectal cancers in young patients.
在最近的研究中，有报道称年轻患者的结直肠癌中微卫星不稳定性频率较高，但年轻患者结直肠癌中微卫星不稳定性（MSI）和染色体不稳定性的频率尚未完全阐明。仅有一份报告显示，在含有肿瘤抑制基因p16的9p位点杂合性缺失（LOH）比率增加。对年轻患者结直肠癌中的LOH和MSI状态进行了检测。
对25例年龄在40岁以下诊断为结直肠癌的患者，使用17个微卫星标记检测MSI和LOH，并用免疫组织化学评估p16表达模式，通过甲基化特异性PCR评估p16基因的甲基化状态。
仅1例（4%）观察到MSI。2p、5q、9p、11q、17p和18q位点的LOH分别在41%、59%、42%、35%、46%和56%的病例中观察到。83%的患者表现出p16阳性表达模式。年轻患者的结直肠癌中有50%（3/6）表现出p16甲基化。
我们的研究表明，无MSI的年轻患者结直肠癌在9p位点显示出高频率的LOH。然而，9p位点的LOH状态与p16表达模式未显示出显著相关性。除p16外，9p上的其他肿瘤抑制基因可能在年轻患者结直肠癌的致癌过程中起重要作用。
