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J Hepatol. 2003 Aug;39(2):215-21.

Diagnosis of intrahepatic metastasis and multicentric carcinogenesis by microsatellite loss of heterozygosity in patients with multiple and recurrent hepatocellular carcinomas.

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  • 1Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.



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.


Using LOH analysis of 15 specific DNA microsatellite loci, tumor clonality was assessed in 37 cases.


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).


Genetic diagnosis by LOH analysis may be more strict and specific than histopathological diagnosis in the differential diagnosis of IM and MC.

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