c-myc amplification in hepatocellular carcinoma predicts unfavorable prognosis.
Structural alterations and amplifications of the c-myc oncogene have been implicated in the pathogenesis and progression of several human neoplastic diseases. To study the role of c-myc amplification in human hepatocellular carcinomas (HCC), we analyzed 20 HCC using differential polymerase chain reaction (PCR). DNA used for differential PCR was extracted from formalin-fixed, paraffin-embedded tissue obtained by radiographically directed needle aspiration biopsy. Differential PCR reactions included sets of primers for c-myc and a control gene, dopamine D2 receptor (D2R), which yielded products of 150 bp and 110 bp, respectively. Evaluation of amplification was based on the relative concentration of c-myc and D2R PCR products. The c-myc amplification was detected in 10 of 20 HCC. Cases with c-myc amplification tended to have higher histologic grade and were significantly (P = 0.05) associated with worse prognosis. Amplification was present in none of two Grade 1 tumors, seven of the fourteen Grade 2 tumors, and three of four Grade 3 tumors. The mean survival times (+/- SEM) for patients with and without c-myc amplification were 5.7 (+/- 1.8) and 13.8 (+/- 2.6) months, respectively. These results indicate that c-myc amplification in HCC can be evaluated by differential PCR of needle biopsy specimens, and is an unfavorable prognostic indicator.
Abou-Elella
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Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
Gramlich
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T
Fritsch
C
C
Gansler
T
T
D000328:Adult; D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011379:Prognosis