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Hepatocyte nuclear factor 1β is a novel prognostic marker independent of the milan criteria in transplantable hepatocellular carcinoma: A retrospective analysis based on tissue microarrays
Author(s) -
Shim Ju Hyun,
Lee Han Chu,
Han Seungbong,
Kang Hyo Jeong,
Yu Eunsil,
Lee SungGyu
Publication year - 2013
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.23584
Subject(s) - medicine , milan criteria , hepatocellular carcinoma , tissue microarray , receiver operating characteristic , proportional hazards model , liver cancer , oncology , univariate analysis , gastroenterology , cancer , immunohistochemistry , retrospective cohort study , multivariate analysis , survival analysis , liver transplantation , transplantation
We retrospectively investigated the prognostic value of hepatocyte nuclear factor 1 ( HNF1 ) proteins in 159 liver transplant patients with hepatocellular carcinoma ( HCC ), including 36 (22.6%) exceeding the Milan criteria. The expression of alpha‐fetoprotein ( AFP ), HNF1α , and HNF1β was examined with immunohistochemistry on duplicate tissue microarray slides containing HCC tumor explants. The times to recurrence and cancer death were analyzed with a Cox regression model and were compared according to the expression of markers of interest. We compared risk predictions with area under the receiver operator curves ( AUROCs ) and C statistics. AFP , HNF1α , and HNF1β were positive in 22.6%, 46.5%, and 61.0% of the tumor immunoprofiles, respectively. Although several variables were associated with the times to recurrence and cancer death in univariate Cox analyses, only AFP expression for the time to recurrence and the Milan criteria and HNF1 β expression for the times to recurrence and cancer death remained significant after multivariate adjustments. The expression of HNF1β (but not HNF1α ) was related to a serum AFP level ≥ 200 ng/mL, microvascular invasion, and AFP expression ( P < 0.05 for all). A subgroup analysis showed that in the group meeting the Milan criteria, recurrence and cancer death rates at 10 years in the HNF1 β‐negative patients were approximately one‐tenth of those in the HNF1 β‐positive patients, but the difference was not significant in the group exceeding the Milan criteria. The addition of HNF1 β expression to the Milan criteria increased the C statistics and AUROCs for both recurrence and mortality ( P < 0.05 for all). In conclusion, the immunohistological detection of HNF1β predicts recurrence and HCC ‐specific death after transplantation and provides an additive benefit in comparison with the Milan selection criteria on their own. Liver Transpl 19:336–345, 2013 . © 2013 AASLD.