title: Cyclooxygenase-2 expression in chronic liver diseases and hepatocellular carcinoma: an immunohistochemical study .
abstract: Hepatocarcinogenesis is a multistep process characterized by hepatocyte inflammation, regeneration, and proliferation. These changes are believed to depend on the aberrant expression of various tumor suppressor genes, oncogenes and growth factors. Several studies have shown the involvement of cyclooxygenase-2 (COX-2), the inducible isoform of the enzymes that catalyze prostaglandin synthesis in various aspects of carcinogenesis. COX-2 has been described as being overexpressed in hepatocellular carcinoma (HCC) patients. Using immunohistochemistry, we studied COX-2 expression in different chronic liver diseases (CLD) including nonalcoholic steatohepatitis (NASH), chronic hepatitis (CH), liver cirrhosis (LC), and HCC in a population referred to a tertiary center in western Sicily, an area moderately endemic for CLD. Sixteen NASH, 35 CH, 15 LC, and 21 HCC samples were analyzed. Positive signs of COX-2 were observed in the cytoplasm of hepatocytes and median values were 6 (3-9) for NASH, 7 (3-9) for CH, 6 (4-9) for LC, and 4 (0-7) for HCC. COX-2 expression was significantly lower in HCC than in NASH (P < 0.001), CH (P < 0.0001), and LC (P < 0.0001). In HCC we found a wide range of COX-2 expression: from no expression in poorly differentiated areas to a high expression in well-differentiated ones, with an inverse correlation between COX-2 and tumor grading, according to Edmonson (rho=-0.67, P < 0.0001).
  
  
  CONCLUSIONS
  (a) COX-2 expression was significantly lower in HCC than in the other CLD; (b) COX-2 expression inversely correlated with tumor differentiation status. These results suggest that COX-2 expression could be related to the inflammatory phenomena present in the early phases of CLD and eventually to the induction of hepatocarcinogenesis.
authors.affiliation: Department of Clinical Medicine and Emerging Pathologies, University of Palermo, Italy. lydiagiannitp@gmail.com
authors.forename: Lydia
authors.initials: L
authors.lastname: Giannitrapani
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ingrao
authors.forename: Maurizio
authors.initials: M
authors.lastname: Soresi
authors.forename: Ada Maria
authors.initials: AM
authors.lastname: Florena
authors.forename: Emanuele
authors.initials: E
authors.lastname: La Spada
authors.forename: Luigi
authors.initials: L
authors.lastname: Sandonato
authors.forename: Natale
authors.initials: N
authors.lastname: D'Alessandro
authors.forename: Melchiorre
authors.initials: M
authors.lastname: Cervello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalto
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002908:Chronic Disease; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008107:Liver Diseases / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged
chemical_list: D051546:Cyclooxygenase 2