Journal Article

Morphometric Analysis of Mast Cells in Tumor Predicts Recurrence of Hepatocellular Carcinoma After Liver Transplantation

W. Sieghart, Michael Trauner, Tobias Meischl, Kaoru Tsuchiya, Matthias Pinter, Judith Stift, Erika Jensen-Jarolim, Markus Peck-Radosavljevic, Gerald Timelthaler, Martina Salzmann, Merima Herac, Nataliya Rohr-Udilova, Rolf Schulte-Hermann, Katharina Wöran, Robert Eferl

2021

Overview

Tumor‐infiltrating immune cells are relevant prognostic and immunotherapeutic targets in hepatocellular carcinoma (HCC). Mast cells play a key role in allergic response but may also be involved in anticancer immunity. Digital morphometric analysis of patient tissue sections has become increasingly available for clinical routine and provides unbiased quantitative data. Here, we apply morphometric analysis of mast cells to retrospectively evaluate their relevance for HCC recurrence in patients after orthotopic liver transplantation (OLT). A total of 173 patients underwent OLT for HCC at the Medical University of Vienna (21 women, 152 men; 55.2 ± 7.9 years; 74 beyond Milan criteria, 49 beyond up‐to‐7 criteria for liver transplantation). Tissue arrays from tumors and corresponding surrounding tissues were immunohistochemically stained for mast cell tryptase. Mast cells were quantified by digital tissue morphometric analysis and correlated with HCC recurrence. Mast cells were detected in 93% of HCC tumors and in all available surrounding liver tissues. Tumor tissues revealed lower mast cell density than corresponding surrounding tissues (P < 0.0001). Patients lacking intratumoral mast cells (iMCs) displayed larger tumors and higher tumor recurrence rates both in the whole cohort (hazard ratio [HR], 2.74; 95% confidence interval [CI], 1.09‐6.93; P = 0.029) and in patients beyond transplant criteria (Milan HR, 2.81; 95% CI, 1.04‐7.62; P = 0.01; up‐to‐7 HR, 3.58; 95% CI, 1.17‐10.92; P = 0.02). Notably, high iMC identified additional patients at low risk classified outside the Milan and up‐to‐7 criteria, whereas low iMC identified additional patients at high risk classified within the alpha‐fetoprotein French and Metroticket criteria. iMCs independently predicted tumor recurrence in a multivariate Cox regression analysis (Milan HR, 2.38; 95% CI, 1.16‐4.91; P = 0.019; up‐to‐7 HR, 2.21; 95% CI, 1.05‐4.62; P = 0.035). Conclusion: Hepatic mast cells might be implicated in antitumor immunity in HCC. Morphometric analysis of iMCs refines prognosis of HCC recurrence after liver transplantation. We applied digital morphometric analysis to evaluate microscopic tissue images of mast cells in tumors and surrounding tissues of hepatocellular carcinoma patients who underwent liver transplantation. We found that intratumoral mast cell density is an independent prognostic factor of HCC recurrence. Mast cells were decreased in tumors as compared to surrounding tissues; lack of mast cells indicated higher tumor recurrence risk. To our best knowledge, this is the first report on the link between hepatic mast cells and HCC recurrence after transplantation. These data also suggest that hepatic mast cells might be implicated in anti‐tumor immunity in HCC.

• Publisher: Ovid Technologies (Wolters Kluwer Health),Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins,John Wiley and Sons Inc,Wolters Kluwer Health/LWW
• Subject: Ablation / Carcinoma, Hepatocellular / Carcinoma, Hepatocellular - immunology / Carcinoma, Hepatocellular - pathology / Carcinoma, Hepatocellular - surgery / Cholangitis / Confidence intervals / Digitization / Diseases of the digestive system. Gastroenterology / Female / Gene expression / Hepatitis B / Hepatitis C / Humans / Immunoglobulins / Liver cancer / Liver diseases / Liver Neoplasms / Liver Neoplasms - immunology / Liver Neoplasms - pathology / Liver Neoplasms - surgery / Liver Transplantation / Liver transplants / Male / Mast Cells / Mast Cells - pathology / Medical prognosis / Middle Aged / Neoplasm Recurrence, Local / Neoplasm Recurrence, Local - immunology / Original / Patients / Postoperative Period / Predictive Value of Tests / Prognosis / Proportional Hazards Models / RC799-869 / Retrospective Studies / Risk Assessment / Software / Transplants & implants / Treatment Outcome / Tumors