Abstract
AimsHepatitis B Virus (HBV) infection is the major risk factor for hepatocellular carcinoma (HCC) in East Asia. Here we aimed to further investigate the abundance of viral antigen and DNA within HBV-related HCC and surrounding tissues at histological level.MethodIn addition to routine histopathology, in situ hybridization (ISH) of HBV DNA and immunohistochemistry (IHC) of HBsAg were performed in tissues from 131 HBsAg-positive HCC patients undergoing liver resection. Serum α-fetoprotein together with basic biochemical and immunological parameter was also measured.ResultsOverall, the ISH of HBV DNA and IHC of HBsAg showed 31.3% and 92.9% positive rate respectively (p < 0.0001). The level of correlation between these two markers was much more significant in tumor (p < 0.0001) than in tumor-surrounding tissue (p = 0.01). HBsAg exhibited a much higher positive rate in tumor-adjacent tissue than in tumor tissue (86.6% versus 29.9%, p < 0.0001) with significantly different staining pattern. By contrast, the positive rate of HBV DNA ISH was comparable in tumor and surrounding tissue (17.6% versus 22.9%, p = 0.36). Yet the HBV DNA signal in tumor tissue showed predominant nuclear localization (87.0%) whereas staining pattern in adjacent tissue was mixed (43.3% nuclear localization, p = 0.0015). Finally, no significant association between intra-tumor HBV DNA/HBsAg positivity and major histological markers (microvascular invasion, tumor differentiation, etc.) or recurrence after surgery was observed.ConclusionsThese data confirmed the largely integrated state of HBV DNA, weaker expression and altered localization of surface antigen in tumor compared with surrounding tissue. The strikingly different prevalence and localization of HBsAg and HBV DNA reflected the complex and heterogeneous mechanisms leading to HBV-induced tumorigenesis.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common cause of cancer and second most frequent cause of cancer-related death globally with 854,000 newZheng et al Diagnostic Pathology (2022) 17:11 is widely accepted as the direct oncogenic event contributing to HCC
The positive rate of Hepatitis B Virus (HBV) DNA in situ hybridization (ISH) was comparable in tumor and surrounding tissue (17.6% versus 22.9%, p = 0.36)
No significant association between intra-tumor HBV DNA/HBsAg positivity and major histological markers or recurrence after surgery was observed. These data confirmed the largely integrated state of HBV DNA, weaker expression and altered localization of surface antigen in tumor compared with surrounding tissue
Summary
Hepatocellular carcinoma (HCC) is one of the most common cause of cancer and second most frequent cause of cancer-related death globally with 854,000 newZheng et al Diagnostic Pathology (2022) 17:11 is widely accepted as the direct oncogenic event contributing to HCC. Hepatocellular carcinoma (HCC) is one of the most common cause of cancer and second most frequent cause of cancer-related death globally with 854,000 new. Previous studies had been conducted to analyze the viral DNA in normal and tumor tissue in all stages of HBV-related diseases [5, 6, 8,9,10,11,12,13,14], there is generally a lack of molecular investigations taking histological features into account. It is highly correlative to the vigor of viral replication in chronic hepatitis B [16]. By using this methodology, we aimed to further analyze the histological features of HBV DNA together with viral surface protein in HCC patients
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