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DOI: 10.1055/s-0037-1612800
Evolutionary distance predicts recurrence after liver transplantation in multifocal hepatocellular carcinoma
Publication History
Publication Date:
03 January 2018 (online)
Question:
Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma in cirrhosis as it treats both the tumour and the underlying premalignant condition. However, patients where HCC is already a systemic disease, LTx may be individually harmful and has a negative impact on donor organ usage. There is thus a need for improved selection criteria beyond nodule morphology to select patients with a favourable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide SNP data between tumour nodules and the cirrhotic liver may be a predictor of survival after liver transplantation for multifocal HCC.
Methods:
In a retrospective multicentre study, clinical data and formalin fixed paraffin embedded (FFPE) specimens of the liver and two tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from FFPE specimens followed by genome wide SNP genotyping.
Results:
Genotype quality criteria allowed the analysis of 8 patients in the discovery and 17 patients 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 datasets (p = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined p = 0.0002). In a post-hoc Cox regression analysis, evolutionary distance (p = 7.4 × 10 – 6), microvascular invasion (p = 1.31 × 10 – 5) captured the survival information in a multivariate model.
Conclusions:
Evolutionary distance allows the definition of a high-risk group of recurrence if preoperative liver biopsy is considered.
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