title: Microsatellite alterations in liver fluke related cholangiocarcinoma are associated with poor prognosis.
abstract: We have characterized the role of genetic alterations in the development of liver fluke related cholangiocarcinoma. We analyzed the loss of heterozygosity (LOH) and microsatellite instability (MSI) of hMSH2, hMLH1, and p53 genes in 55 patients with intrahepatic cholangiocarcinoma by using polymerase chain reaction based microsatellite markers D2S119, D3S1611, and TP53, respectively and determined the association between microsatellite alterations and patient survival. A total of 27 (49.1%) out of 55 cases exhibited microsatellite alterations in one locus or more. Of 55 samples, 11 (20%) demonstrated MSI at D2S119 and four (7%) showed MSI at D3S1611. LOH was shown in seven out of 36 (19%) informative cases for D3S1611 and 16 out of 50 (32%) for TP53. Microsatellite alterations at loci studied were significantly associated with poor survival (P=0.0098). This study suggests that genetic alterations of DNA mismatch repair genes and tumor suppressor gene p53 may be involved in cholangiocarcinogenesis and these alterations may be of value as prognostic indicators for liver fluke related cholangiocarcinoma.
authors.affiliation: Department of Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand. temduang@kku.ac.th
authors.forename: Temduang
authors.initials: T
authors.lastname: Limpaiboon
authors.forename: Kamoltip
authors.initials: K
authors.lastname: Krissadarak
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.forename: Patcharee
authors.initials: P
authors.lastname: Jearanaikoon
authors.forename: Vajarabhongsa
authors.initials: V
authors.lastname: Bhuhisawasdi
authors.forename: Siri
authors.initials: S
authors.lastname: Chau-in
authors.forename: Amornrat
authors.initials: A
authors.lastname: Romphruk
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D001653:Bile Ducts, Intrahepatic; D002352:Carrier Proteins; D018281:Cholangiocarcinoma / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D004268:DNA-Binding Proteins; D005211:Fascioliasis / Q000150:complications*; D005260:Female; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein