Comparative genomic hybridization of hepatocellular carcinoma: correlation with fluorescence in situ hybridization in paraffin-embedded tissue.
BACKGROUND
Proto-oncogene MYC, mapped to chromosomal band 8q24 and the genes for hepatocyte growth factor (HGF at 7q21) and its receptor, MET, at chromosomal band 7q31, have an important role in the biology and growth of normal and neoplastic liver. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies have reported frequent abnormalities of chromosomes 1 and 8 in hepatocellular carcinomas (HCCs) of various clinical and pathological stages. Chromosome 7 involvement is reported to be less frequent.


METHODS
Frozen tissue from 17 HCCs was used for CGH analysis and sections of corresponding formalin-fixed, paraffin-embedded HCC tissue were used for dual-color FISH with locus-specific (LSI-cMYC for chromosome 8q24 and LSI D7S486 for chromosome 7q31) and centromeric probes, CEP8 (8p11.1-q11.2) and CEP7 (7p11.1-q11.2) (Vysis, Inc, Downers Grove, IL). This study intended to determine the pattern of chromosomal aberrations in early-stage (incidental) HCC and large surgically resected HCC, and also compared the efficiency and usefulness of the two cytogenetic methods.


RESULTS
CGH showed abnormalities on chromosomes 1q, 5q, 7q, 8q, 9, 10, 13q, 15, 16, 17p, 18q, 19, 20, 21, 22, and X. Gains of 8q were noted in 50% of the HCCs, including five cases of incidental HCCs by CGH. Increase in copy numbers of MYC detected by FISH was noted in 25% of tumors that had shown 8q gains by CGH and in five cases with no chromosome abnormalities noted by CGH. Three cases with 7q31 copy number abnormalities were found by FISH in addition to those detected by CGH.


CONCLUSIONS
Combined use of CGH and FISH may provide important information about early and/or primary genetic changes in the development of HCC.
Department of Pathology, Presbyterian University Hospital, University of Pittsburgh Medical Center, PA 15213, USA. raounm@MSX.UPMC.EDU
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Rao
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Gollin
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Beaves
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Cieply
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Nalesnik
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Michalopoulos
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000556:secondary; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods*; D016612:Paraffin Embedding; D000090063:Proto-Oncogene Mas