title: Expression levels of insulin-like growth factors and receptors in hepatocellular carcinoma: a retrospective study.
abstract: BACKGROUND
  The insulin-like growth factor (IGF) pathway is implicated in the pathogenesis of hepatocellular carcinoma (HCC) and may be important in nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine expression levels of IGFs and receptors in NAFLD-associated HCC.
  
  
  METHODS
  Tissue microarrays were constructed from patients who underwent hepatectomy for HCC. Immunohistochemistry was performed using antibodies for IGF ligands and receptors. Immunostain results were scored by a pathologist blinded to clinical data.
  
  
  RESULTS
  Among 27 patients with HCC, the most common underlying liver diseases included NAFLD, hepatitis C, and alcoholic hepatitis. Expression levels of IGFs and receptors were not associated with patients' underlying liver disease. In all patients, IGF-2 expression was upregulated in tumor and adjacent non-neoplastic liver. Expression of IGF-1 was low in adjacent liver in 6 of 10 patients with cirrhosis, compared with 2 of 17 patients without cirrhosis (P = 0.025). Higher IGF-1 expression in liver adjacent to tumor was associated with poorer median survival of 22 months, compared with 72 months with equal or lower IGF-1 expression in adjacent liver relative to tumor (P = 0.006).
  
  
  CONCLUSIONS
  Our preliminary results demonstrate significant associations between IGF-1 expression and liver cirrhosis and survival after resection in patients with HCC, independent of their underlying liver disease.
authors: Hepato-Pancreato-Biliary Programs, Virginia Piper Cancer Institute, 800 E, 28th Street, Suite 602, Minneapolis, MN 55407, USA. ys475@yahoo.com.
authors: Yun Shin
authors: YS
authors: Chun
authors: Min
authors: M
authors: Huang
authors: Lori
authors: L
authors: Rink
authors: Margaret
authors: M
authors: Von Mehren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000502:physiology; D006526:Hepatitis C / Q000150:complications / Q000473:pathology / Q000821:virology; D006801:Humans; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000473:pathology / Q000821:virology; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C583557:IGF1 protein, human; C035170:IGF2 protein, human; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1