J Pathol Transl Med.  2018 Sep;52(5):267-274. 10.4132/jptm.2018.07.14.

C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker

• Shin JH
• Yu E
• Kim EN
• Kim CJ

• KMID: 2422092
• DOI: http://doi.org/10.4132/jptm.2018.07.14

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 non-neoplastic 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 non-neoplastic liver tissues obtained from surgically resected, treatment-naïve 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 non-neoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in six cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (p = .031) 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 non-neoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration.

Keyword

Carcinoma, hepatocellular; C-reactive protein; Hepatitis B virus; Immunohistochemistry; Prognosis

MeSH Terms

C-Reactive Protein*
Carcinoma, Hepatocellular*
Hepatitis B virus
Hepatitis B*
Hepatitis B, Chronic
Hepatitis*
Hepatocytes
Humans
Immunohistochemistry
Liver*
Prognosis
Recurrence
C-Reactive Protein

Figure

• 

  Fig. 1. Cytoplasmic C-reactive protein immunoreactivity in non-neoplastic hepatocytes in treatment-naive, surgically resected HBV-associated hepatocellular carcinoma cases. Immunoreactivity was determined using a 4-tier grading system: A–B, grade 0; C–D, grade 1; E–F, grade 2; and G–H, grade 3.

• 

  Fig. 2. Positive correlation between serum C-reactive protein (CRP) level and CRP immunoreactivity grades of non-neoplastic hepatocytes (p<.001; rho=0.513).

• 

  Fig. 3. Relationships between C-reactive protein (CRP) immunoreactivity of hepatocytes and patient outcomes. (A) There is a significant difference in cancer-specific survival between patients with CRP grade 3 immunoreactivity and those with CRP grade 0, 1, or 2 immunoreactivity (p=.031). (B) There was a marginal difference in early recurrence of cancer between the 2 groups (p=.050). (C, D) The presence or absence of satellite nodule (C) and vascular invasion (D) shows significant difference in cancer-specific survival period (p<.001 and p=.001, respectively).

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