Diagnosis of intrahepatic metastasis and multicentric carcinogenesis by microsatellite loss of heterozygosity in patients with multiple and recurrent hepatocellular carcinomas.
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.
Morimoto
Osakuni
O
Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nagano
Hiroaki
H
Sakon
Masato
M
Fujiwara
Yoshiyuki
Y
Yamada
Terumasa
T
Nakagawa
Hidewaki
H
Miyamoto
Atsushi
A
Kondo
Motoi
M
Arai
Isao
I
Yamamoto
Tameyoshi
T
Ota
Hideo
H
Dono
Keizo
K
Umeshita
Koji
K
Nakamori
Shoji
S
Sasaki
Yo
Y
Ishikawa
Osamu
O
Imaoka
Shingi
S
Monden
Morito
M
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