Genes & Cancer

Using quantitative immunohistochemistry in patients at high risk for hepatocellular cancer

Sobia Zaidi1, Richard Amdur2, Xiyan Xiang1, Herbert Yu3, Linda L. Wong4, Shuyun Rao1, Aiwu R. He5, Karan Amin1, Daewa Zaheer2, Raj K. Narayan6, Sanjaya K. Satapathy7, Patricia S. Latham8, Kirti Shetty9, Chandan Guha10, Nancy R. Gough1, Lopa Mishra1,2

1 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

2 Department of Surgery, The George Washington University, Washington, DC 20037, USA

3 Department of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI 96813, USA

4 Department of Surgery, University of Hawaii, Honolulu, HI 96813, USA

5 Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA

6 Department of Neurosurgery, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11030, USA

7 Sandra Atlas Bass Center for Liver Diseases and Transplantation, Department of Medicine, North Shore University Hospital/Northwell Health, NY 11030, USA

8 Department of Pathology, The George Washington University, Washington, DC 20037, USA

9 Division of Gastroenterology and Hepatology, University of Maryland, Baltimore, MD 21201, USA

10 Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA


Lopa Mishra,

Nancy R. Gough,

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

Received: January 28, 2022 Accepted: May 20, 2022 Published: June 06, 2022


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.

PII: 220