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JPTM > Ahead-of Print

doi: https://doi.org/10.4132/jptm.2018.07.14    [Epub ahead of print]
C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker
Jin Ho Shin, Eunsil Yu, Eun Na Kim, Chong Jai Kim
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Corresponding Author: Chong Jai Kim ,Tel: +82-2-3010-4516, Email: ckim@amc.seoul.kr
Received: January 23, 2018;  Revised: June 26, 2018  Accepted: July 14, 2018.  Published online: July 27, 2018.
ABSTRACT

Background:
Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Peripheral blood C-reactive protein (CRP) concentration and CRP overexpression in HCC cells are proven to be prognostic markers for HCC, but the significance of CRP expression in nonneoplastic hepatocytes, which are the primary origin of CRP, has not been studied. This study was conducted to determine the clinicopathologic significance of CRP immunoreactivity in the background liver of HBV-associated HCC.
Methods:
CRP immunostaining was done on tissue microarrays of nonneoplastic liver tissues obtained from surgically resected, treatment-naive HBV-associated HCCs (n=156). The relationship between CRP immunoreactivity and other clinicopathologic parameters including cancer-specific survival was analyzed. CRP immunoreactivity was determined using a 4-tier grading system: grades 0, 1, 2, and 3.
Results:
CRP was positive in 139 of 156 cases (89.1%) of nonneoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in 6 cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (P=.0031) and a tendency for shorter interval before early recurrence (P=.050). The degree of CRP immunoreactivity correlated with serum CRP concentration (P<.001).
Conclusions:
CRP immunoreactivity in nonneoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration.
Key Words: Hepatocellular carcinoma; C-reactive protein; Hepatitis B virus; Immunohistochemistry; Prognosis