title: CYP1A2 is a predictor of HCC recurrence in HCV-related chronic liver disease: A retrospective multicentric validation study.
abstract: BACKGROUND
  Although hepatic resection is a potentially curative treatment for hepatocellular carcinoma (HCC), post-operative prognosis remains unsatisfactory due to the high incidence of recurrence. Several clinicopathological markers have been associated with HCC recurrence, but none has been validated. Extratumoral expression of cytochrome P4501A2 (CYP1A2) was recently proposed as predictor of HCC recurrence.
  
  
  OBJECTIVE
  To validate extratumoral CYP1A2 as predictor of HCC recurrence and to determine its applicability to pretreatment liver biopsy.
  
  
  METHODS
  Surgically resected HCC (n.180) with clinicopathological data and follow up were retrospectively studied (HCV n.54; HBV n.91; NAFLD/NASH n.35). CYP1A2 expression was evaluated using an immunohistochemical assay and semiquantitative analysis.
  
  
  RESULTS
  Etiology-stratified analysis showed that low CYP1A2 expression was independently associated with recurrence-free survival in HCV patients (HR 2.814, 95% CI 1.300-6.093, p=0.009); this association was lost in the whole cohort. Pretreatment liver biopsy and paired surgical specimens showed concordant CYP1A2 expression in the vast majority of cases (87%), with NPV of 100%, PPV of 81.25%, and a Cohen kappa of 0.72 (substantial agreement).
  
  
  CONCLUSIONS
  We validated the extratumoral expression of CYP1A2 as a biomarker of HCC recurrence in HCV patients. CYP1A2 analysis in pretreatment liver biopsy can be of help to stratify HCC patients for personalized treatment.
authors.affiliation: University of Milan School of Medicine, Milan, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Sciarra
authors.affiliation: University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Pintea
authors.affiliation: Pathology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Nahm
authors.affiliation: Humanitas Clinical and Research Center, Hepatobiliary and General Surgery, Rozzano, Milano, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Donadon
authors.affiliation: Humanitas Clinical and Research Center, Biostatistics Unit, Rozzano, Milano, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Morenghi
authors.affiliation: Pathology, Fondazione IRCCS Ca' Granda Ospedale Policlinico, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Maggioni
authors.affiliation: Hepato-Gastroenterology and Digestive Oncology, Saint André Hospital CHU Bordeaux and Inserm UMR 1053, Bordeaux University, Bordeaux, France.
authors.forename: Jean Frederic
authors.initials: JF
authors.lastname: Blanc
authors.affiliation: Humanitas Clinical and Research Center, Hepatobiliary and General Surgery, Rozzano, Milano, Italy; Humanitas University, Department of Biomedical Sciences, Rozzano, Milano, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Torzilli
authors.affiliation: Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Yeh
authors.affiliation: Pathology, CHU de Bordeaux, Pellegrin Hospital, Bordeaux, France and Inserm UMR 1053, Bordeaux University, Bordeaux, France.
authors.forename: Paulette
authors.initials: P
authors.lastname: Bioulac-Sage
authors.affiliation: Pathology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
authors.affiliation: Humanitas Clinical and Research Center, Pathology Unit, Rozzano, Milano, Italy; Humanitas University, Department of Biomedical Sciences, Rozzano, Milano, Italy. Electronic address: massimo.roncalli@hunimed.eu.
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
authors.affiliation: Humanitas Clinical and Research Center, Pathology Unit, Rozzano, Milano, Italy; Humanitas University, Department of Biomedical Sciences, Rozzano, Milano, Italy. Electronic address: luca.di_tommaso@hunimed.eu.
authors.forename: Luca
authors.initials: L
authors.lastname: Di Tommaso
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000601:surgery; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D005260:Female; D006498:Hepatectomy; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D015994:Incidence; D007558:Italy; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2
keywords: CYP1A2; HCC; Immunocytochemistry; Liver biopsy; Outcome; Translational biomarkers