title: Determination of the molecular relationship between multiple tumour nodules in hepatocellular carcinoma differentiates multicentric origin from intrahepatic metastasis.
abstract: The purpose of this study was to determine the molecular relationship between multiple tumour nodules in hepatocellular carcinoma (HCC) within individual patients and to evaluate their clonality, which may bear prognostic significance. In 25 HCC nodules from 11 patients with multiple HCCs, the clonal relationships of the nodules within individual patients were determined using DNA fingerprinting with loss of heterozygosity (LOH) assay, comparative genomic hybridization (CGH), and hepatitis B virus (HBV) integration pattern. Both LOH assay and CGH indicated that in four (36%) of the 11 patients, the multiple HCCs had different clonalities and hence were of multicentric origin, whereas in the remaining seven (64%) patients, the multiple HCCs had similar clonal relationships and were intrahepatic metastases. In selected cases, the HBV integration pattern helped to confirm the clonality results. Gross appearance, size, location, and histology of the tumours could not accurately predict their clonal origin in every case. Assessment of DNA alterations allows precise determination of the clonality of multiple HCCs within one patient. Of these molecular methods, LOH analysis can be used to evaluate tumour clonality in most patients even before surgical resection, since this assay can be readily applied routinely to either liver biopsies or fine needle aspirates.
authors.affiliation: Department of Pathology, The University of Hong Kong, Faculty of Medicine, Queen Mary Hospital, Hong Kong. iolng@hku.hk
authors.forename: Irene Oi-lin
authors.initials: IO
authors.lastname: Ng
authors.forename: Xin-yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Ronnie Tung-ping
authors.initials: RT
authors.lastname: Poon
authors.forename: Sheung-Tat
authors.initials: ST
authors.lastname: Fan
authors.forename: Joyce Man-Fong
authors.initials: JM
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D006515:Hepatitis B virus / Q000302:isolation & purification; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary* / Q000821:virology; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D016662:Virus Integration
chemical_list: D004273:DNA, Neoplasm; D004279:DNA, Viral