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SHR Neuro Cancer Cardio Lipid Metab Microb
Heits, N; Brosch, M; Herrmann, A; Behrens, R; Röcken, C; Schrem, H; Kaltenborn, A; Klempnauer, J; Kreipe, HH; Reichert, B; Lenschow, C; Wilms, C; Vogel, T; Wolters, H; Wardelmann, E; Seehofer, D; Buch, S; Zeissig, S; Pannach, S; Raschzok, N; Dietel, M; von Schoenfels, W; Hinz, S; Teufel, A; Evert, M; Franke, A; Becker, T; Braun, F; Hampe, J; Schafmayer, C.
Evolutionary Distance Predicts Recurrence After Liver Transplantation in Multifocal Hepatocellular Carcinoma.
Transplantation. 2018; 102(10): e424-e430-e424-e430.
Doi: 10.1097/TP.0000000000002356
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- Co-authors Med Uni Graz
- Schrem Harald Heinrich
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- Abstract:
- 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. 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. 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. Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered.