title: Diagnosis of intrahepatic metastasis and multicentric carcinogenesis by microsatellite loss of heterozygosity in patients with multiple and recurrent hepatocellular carcinomas.
abstract: OBJECTIVE
  The prognosis of hepatocellular carcinoma (HCC) is poor because of frequent intrahepatic metastasis (IM) or multicentric carcinogenesis (MC). We compared the effectiveness of loss of heterozygosity (LOH) analysis in the diagnosis of these two forms with that of histopathological diagnosis.
  
  
  METHODS
  Using LOH analysis of 15 specific DNA microsatellite loci, tumor clonality was assessed in 37 cases.
  
  
  RESULTS
  LOH was observed in 30% of seven solitary tumors. According to these results, the selected threshold to diagnose MC was a difference in the LOH status at more than 30% of the analyzed loci, when comparing two samples in the same liver. In nine multiple HCCs, identical genetic and histopathological diagnoses were found in four (IM: 2, MC: 2). Of 21 recurrent tumors, 19 showed LOH for at least one marker. IM and MC were genetically diagnosed in five and ten patients, respectively. Genetic and histopathological diagnoses were identical in ten of 19 patients (IM: 5. MC: 5). Five genetic MC were histopathologically diagnosed as IM (3) and 'undetermined' (2).
  
  
  CONCLUSIONS
  Genetic diagnosis by LOH analysis may be more strict and specific than histopathological diagnosis in the differential diagnosis of IM and MC.
authors.affiliation: Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Osakuni
authors.initials: O
authors.lastname: Morimoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Masato
authors.initials: M
authors.lastname: Sakon
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Terumasa
authors.initials: T
authors.lastname: Yamada
authors.forename: Hidewaki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Motoi
authors.initials: M
authors.lastname: Kondo
authors.forename: Isao
authors.initials: I
authors.lastname: Arai
authors.forename: Tameyoshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Ota
authors.forename: Keizo
authors.initials: K
authors.lastname: Dono
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.forename: Yo
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishikawa
authors.forename: Shingi
authors.initials: S
authors.lastname: Imaoka
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000556:secondary*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015995:Prevalence