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Transplantation. 2018 Oct;102(10):e424-e430. doi: 10.1097/TP.0000000000002356.

Evolutionary Distance Predicts Recurrence After Liver Transplantation in Multifocal Hepatocellular Carcinoma.

Author information

1
Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
2
Medical Department 1, University Hospital Dresden, TU Dresden, Dresden, Germany.
3
Institute for Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
4
Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany.
5
Core Facility Quality Management and Health Technology Assessment in Transplantation, Integrated Research Treatment Center-Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
6
Department of Trauma and Orthopaedic Surgery, Federal Armed Forces Hospital Westerstede, Germany.
7
Institute of Pathology, Hannover Medical School, Hannover, Germany.
8
Department of General Surgery and Visceral Surgery, University Hospital of Muenster, Muenster, Germany.
9
Clinic for Transplantation Medicine, University Hospital of Muenster, Muenster, Germany.
10
Department for Visceral and General Surgery, St. Josefs Hospital Dortmund-Hoerde, Germany.
11
Department of Pathology, University Hospital of Muenster, Muenster, Germany.
12
Department of General, Visceral, and Transplantation Surgery, Charité, Campus Virchow Klinikum, Berlin, Germany.
13
Institute of Pathology, Charité University Hospital, Berlin, Germany.
14
Department of Medicine, University Hospital Regensburg, Regensburg, Germany.
15
Institute of Pathology, University of Regensburg, Regensburg, Germany.
16
Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Abstract

BACKGROUND:

Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single-nucleotide polymorphism data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after LTx for multifocal HCC.

METHODS:

In a retrospective multicenter study, clinical data and formalin-fixed paraffin-embedded specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from formalin-fixed paraffin-embedded specimens followed by genome wide single-nucleotide polymorphism genotyping.

RESULTS:

Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (P = 0.04) and in the replication data sets (P = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined P = 0.0002). In a univariate analysis, evolutionary distance (P = 7.4 × 10) and microvascular invasion (P = 1.31 × 10) were significantly associated with survival in a Cox regression analysis.

CONCLUSIONS:

Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered.

PMID:
29994984
DOI:
10.1097/TP.0000000000002356
[Indexed for MEDLINE]

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