Low CD8+ Density Variation and R1 Surgical Margin as Independent Predictors of Early Post-Resection Recurrence in HCC Patients Meeting Milan Criteria

Authors

Rokas Stulpinas, Institute of Biomedical Sciences, Department of Pathology and Forensic Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania.
Ieva Jakiunaite, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania.
Agne Sidabraite, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania.
Allan Rasmusson, Institute of Biomedical Sciences, Department of Pathology and Forensic Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania.
Dovile Zilenaite-Petrulaitiene, Institute of Biomedical Sciences, Department of Pathology and Forensic Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania.
Kestutis Strupas, Institute of Clinical Medicine, Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Vilnius University, 01513 Vilnius, Lithuania.
Arvydas Laurinavicius, Institute of Biomedical Sciences, Department of Pathology and Forensic Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania.
Aiste Gulla, Institute of Clinical Medicine, Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Vilnius University, 01513 Vilnius, Lithuania.

Document Type

Journal Article

Publication Date

9-10-2024

Journal

Current oncology (Toronto, Ont.)

Volume

31

Issue

9

DOI

10.3390/curroncol31090394

Keywords

CD8; Milan criteria; digital pathology; hepatocellular carcinoma (HCC); liver transplantation; tumor-infiltrating lymphocytes

Abstract

Our study included 41 patients fulfilling the Milan criteria preoperatively and aimed to identify individuals at high risk of post-resection HCC relapse, which occurred in 18 out of 41 patients (43.9%), retrospectively. We analyzed whole slide images of CD8 immunohistochemistry with automated segmentation of tissue classes and detection of CD8+ lymphocytes. The image analysis outputs were subsampled using a hexagonal grid-based method to assess spatial distribution of CD8+ lymphocytes with regards to the epithelial edges. The CD8+ lymphocyte density indicators, along with clinical, radiological, post-surgical and pathological variables, were tested to predict HCC relapse. Low standard deviation of CD8+ density along the tumor edge and R1 resection emerged as independent predictors of shorter recurrence-free survival (RFS). In particular, patients presenting with both adverse predictors exhibited 100% risk of relapse within 200 days. Our results highlight the potential utility of integrating CD8+ density variability and surgical margin to identify a high relapse-risk group among Milan criteria-fulfilling HCC patients. Validation in cohorts with core biopsy could provide CD8+ distribution data preoperatively and guide preoperative decisions, potentially prioritizing liver transplantation for patients at risk of incomplete resection (R1) and thereby improving overall treatment outcomes significantly.

APA Citation

Stulpinas, Rokas; Jakiunaite, Ieva; Sidabraite, Agne; Rasmusson, Allan; Zilenaite-Petrulaitiene, Dovile; Strupas, Kestutis; Laurinavicius, Arvydas; and Gulla, Aiste, "Low CD8+ Density Variation and R1 Surgical Margin as Independent Predictors of Early Post-Resection Recurrence in HCC Patients Meeting Milan Criteria" (2024). GW Authored Works. Paper 5648.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5648

Department

Surgery