Kawaki J, Miyazaki M, Ito H, Nakagawa K, Shimizu H, Yoshidome H, Uzawa K, Tanzawa H, Nakajima N
First Department of Surgery, Chiba University School of Medicine, Chiba, Japan.
Int J Cancer. 2000 Oct 15;88(2):228-31. doi: 10.1002/1097-0215(20001015)88:2<228::aid-ijc13>3.0.co;2-8.
Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver in Japan. Despite progress in operative techniques and adjuvant therapy, the prognosis of ICC remains very poor. Therefore, it is important to investigate the mechanism of carcinogenesis and progression of ICC. We screened allelic losses at 6 loci, including that of novel tumor-suppressor gene FEZ1 on chromosome 8p, and at 5 microsatellite loci to define the association with tumor-suppressor genes (HNPCC, APC, RB1, p53, DCC) in tumors from 18 unrelated ICC patients by PCR-loss of heterozygosity (LOH) assay and correlated the alterations with clinicopathological parameters. As a result, 61.1% (11 of 18) of patients showed LOH at 1 of the loci at least, and microsatellite instability was observed in 16.7% (3 of 18). At locus D8S258, relatively frequent LOH was detected (17.6%) compared with other loci on chromosome 8p. Among the other 5 chromosomal arms tested, the highest frequency of LOH (23.5%) was observed at D17S153. Fifty percent of cases with the mass-forming + periductal infiltrating type were frequently detected by LOH at D8S258 compared to cases of the mass-forming or intraductal growth type. In conclusion, we show that 1 putative tumor-suppressor gene on 8p22 may relate to progression of ICC and suggest that the p53 tumor-suppressor gene may be associated with carcinogenesis of ICC.
肝内胆管癌（ICC）是日本第二常见的肝脏原发性恶性肿瘤。尽管手术技术和辅助治疗取得了进展，但ICC的预后仍然很差。因此，研究ICC的致癌和进展机制很重要。我们通过聚合酶链反应杂合性缺失（LOH）分析，筛查了包括位于8号染色体p臂上的新型肿瘤抑制基因FEZ1在内的6个位点以及5个微卫星位点的等位基因缺失情况，以确定18例无血缘关系的ICC患者肿瘤中与肿瘤抑制基因（HNPCC、APC、RB1、p53、DCC）的关联，并将这些改变与临床病理参数进行关联分析。结果显示，61.1%（18例中的11例）的患者至少在1个位点出现了LOH，16.7%（18例中的3例）观察到微卫星不稳定。在D8S258位点，与8号染色体p臂上的其他位点相比，检测到相对频繁的LOH（17.6%）。在测试的其他5条染色体臂中，在D17S153位点观察到最高频率的LOH（23.5%）。与肿块形成型或导管内生长型病例相比，肿块形成+导管周围浸润型病例中有50%在D8S258位点频繁检测到LOH。总之，我们表明8p22上的1个假定肿瘤抑制基因可能与ICC进展有关，并提示p53肿瘤抑制基因可能与ICC的致癌作用有关。
