CYP1A2 is a predictor of HCC recurrence in HCV-related chronic liver disease

A retrospective multicentric validation study

Amedeo Sciarra, Bogdan Pintea, Ji Hae Nahm, Matteo Donadon, Emanuela Morenghi, Marco Maggioni, Jean Frederic Blanc, Guido Torzilli, Matthew Yeh, Paulette Bioulac-Sage, Young Nyun Park, Massimo Roncalli, Luca Di Tommaso

Research output: Contribution to journalArticle

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. Aims 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). Conclusion 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.

Original languageEnglish
Pages (from-to)434-439
Number of pages6
JournalDigestive and Liver Disease
Volume49
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

Fingerprint

Validation Studies
Cytochromes
Liver Diseases
Hepatocellular Carcinoma
Chronic Disease
Recurrence
Liver
Biopsy
Biomarkers
Survival
Incidence
Therapeutics

Keywords

  • CYP1A2
  • HCC
  • Immunocytochemistry
  • Liver biopsy
  • Outcome
  • Translational biomarkers

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

CYP1A2 is a predictor of HCC recurrence in HCV-related chronic liver disease : A retrospective multicentric validation study. / Sciarra, Amedeo; Pintea, Bogdan; Nahm, Ji Hae; Donadon, Matteo; Morenghi, Emanuela; Maggioni, Marco; Blanc, Jean Frederic; Torzilli, Guido; Yeh, Matthew; Bioulac-Sage, Paulette; Park, Young Nyun; Roncalli, Massimo; Di Tommaso, Luca.

In: Digestive and Liver Disease, Vol. 49, No. 4, 01.04.2017, p. 434-439.

Research output: Contribution to journalArticle

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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. Aims 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). Conclusion 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.",
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T1 - CYP1A2 is a predictor of HCC recurrence in HCV-related chronic liver disease

T2 - A retrospective multicentric validation study

AU - Sciarra, Amedeo

AU - Pintea, Bogdan

AU - Nahm, Ji Hae

AU - Donadon, Matteo

AU - Morenghi, Emanuela

AU - Maggioni, Marco

AU - Blanc, Jean Frederic

AU - Torzilli, Guido

AU - Yeh, Matthew

AU - Bioulac-Sage, Paulette

AU - Park, Young Nyun

AU - Roncalli, Massimo

AU - Di Tommaso, Luca

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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. Aims 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). Conclusion 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.

AB - 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. Aims 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). Conclusion 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.

KW - CYP1A2

KW - HCC

KW - Immunocytochemistry

KW - Liver biopsy

KW - Outcome

KW - Translational biomarkers

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