Allelic loss in human intrahepatic cholangiocarcinoma: Correlation betweenchromosome 8p22 and tumor progression

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant p rimary tumor of the liver in Japan. Despite progress in operative technique s and adjuvant therapy, the prognosis of ICC remains very poor. Therefore, it is important to investigate the mechanism of carcinogenesis and progress ion of ICC. We screened allelic losses at 6 loci, including that of novel t umor-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 is unrelated ICC patients by PCR-loss of heterozygosity (LOH) assay and correlated the alterations with clinicopathological parame ters. 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, th e highest frequency of LOH (23.5%) was observed at D17S153. Fifty percent o f cases with the mass-forming + periductal infiltrating type were frequentl y detected by LOH at D8S258 compared to cases of the mass-forming or intrad uctal 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 tumo r-suppressor gene may be associated with carcinogenesis of ICC. Int. J. Can cer 88:228-231, 2000. (C) 2000 Wiley-Liss, Inc.