Using quantitative immunohistochemistry in patients at high risk for hepatocellular cancer

Sobia Zaidi, The Institute for Bioelectronic Medicine, The Feinstein Institutes for Medical Research and Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY 11030, USA.
Richard Amdur, Department of Surgery, The George Washington University, Washington, DC 20037, USA.
Xiyan Xiang, The Institute for Bioelectronic Medicine, The Feinstein Institutes for Medical Research and Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY 11030, USA.
Herbert Yu, Department of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
Linda L. Wong, Department of Surgery, University of Hawaii, Honolulu, HI 96813, USA.
Shuyun Rao, The Institute for Bioelectronic Medicine, The Feinstein Institutes for Medical Research and Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY 11030, USA.
Aiwu R. He, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
Karan Amin, The Institute for Bioelectronic Medicine, The Feinstein Institutes for Medical Research and Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY 11030, USA.
Daewa Zaheer, Department of Surgery, The George Washington University, Washington, DC 20037, USA.
Raj K. Narayan, Department of Neurosurgery, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11030, USA.
Sanjaya K. Satapathy, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Department of Medicine, North Shore University Hospital/Northwell Health, NY 11030, USA.
Patricia S. Latham, Department of Pathology, The George Washington University, Washington, DC 20037, USA.
Kirti Shetty, Division of Gastroenterology and Hepatology, University of Maryland, Baltimore, MD 21201, USA.
Chandan Guha, Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Nancy R. Gough, The Institute for Bioelectronic Medicine, The Feinstein Institutes for Medical Research and Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY 11030, USA.
Lopa Mishra, The Institute for Bioelectronic Medicine, The Feinstein Institutes for Medical Research and Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY 11030, USA.

Document Type

Journal Article

Publication Date

1-1-2022

Journal

Genes & cancer

Volume

13

DOI

10.18632/genesandcancer.220

Keywords

cirrhosis; diagnostic model; immunohistochemistry; liver cancer; transforming growth factor beta

Abstract

Hepatocellular carcinoma (HCC) is the primary form of liver cancer and a major cause of cancer death worldwide. Early detection is key to effective treatment. Yet, early diagnosis is challenging, especially in patients with cirrhosis, who are at high risk of developing HCC. Dysfunction or loss of function of the transforming growth factor β (TGF-β) pathway is associated with HCC. Here, using quantitative immunohistochemistry analysis of samples from a multi-institutional repository, we evaluated if differences in TGF-β receptor abundance were present in tissue from patients with only cirrhosis compared with those with HCC in the context of cirrhosis. We determined that TGFBR2, not TGFBR1, was significantly reduced in HCC tissue compared with cirrhotic tissue. We developed an artificial intelligence (AI)-based process that correctly identified cirrhotic and HCC tissue and confirmed the significant reduction in TGFBR2 in HCC tissue compared with cirrhotic tissue. Thus, we propose that a reduction in TGFBR2 abundance represents a useful biomarker for detecting HCC in the context of cirrhosis and that incorporating this biomarker into an AI-based automated imaging pipeline could reduce variability in diagnosing HCC from biopsy tissue.

Department

Surgery

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