Pathology of Hepatocellular Carcinoma and Tumor-Bearing Liver Tissue in Association with hTERT Promoter Mutation

Anne Kristin Fischer; Alexander Semaan; Anna-Lena Wulf; Christian Vokuhl; Diane Goltz; Hans-Peter Fischer

doi:10.1155/2023/4313504

Pathology of Hepatocellular Carcinoma and Tumor-Bearing Liver Tissue in Association with hTERT Promoter Mutation

Int J Hepatol. 2023 Aug 9:2023:4313504. doi: 10.1155/2023/4313504. eCollection 2023.

Authors

Anne Kristin Fischer¹, Alexander Semaan², Anna-Lena Wulf³, Christian Vokuhl³, Diane Goltz⁴, Hans-Peter Fischer^{3

5}

Affiliations

¹ Institute of Pathology, University of Cologne, Kerpener Str. 62 50937, Germany.
² Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany.
³ Institute of Pathology, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany.
⁴ Institute of Pathology and Hematopathology Hamburg, Fangdieckstraße 75a, 22547 Hamburg, Germany.
⁵ Institute of Pathology Troisdorf, Mendener Str. 12, 53840 Troisdorf, Germany.

Abstract

Background: The hTERT promoter mutation represents a common and early event in hepatocarcinogenesis, but its linkage to the morphological status of the underlying liver tissue is poorly understood. We analyzed the connection between the histopathological changes in tumor-bearing liver tissue and the occurrence of the hTERT promoter mutation in hepatocellular carcinoma (HCC), correlated with clinical data.

Methods: The study cohort comprised 160 histologically confirmed HCC in patients with or without cirrhosis that were investigated for the hTERT promoter mutation. We evaluated the frequency of the hTERT promoter mutation in patients with HCC with or without cirrhosis and correlated it with potential clinical and histopathological drivers. In particular, we examined tumor-bearing noncirrhotic liver tissue regarding inflammation; the modified histological activity index (mHAI), fibrosis, and steatosis; and its correlation with the frequency of the hTERT promoter mutation in HCC. We evaluated overall survival with multivariate Cox regression. Furthermore, we compared hTERT antibody immunohistochemistry and molecular hTERT promoter mutation analysis of both HCC and background liver tissue.

Results: The hTERT promoter mutation was especially related to HCC in cirrhotic compared with noncirrhotic liver (p < 0.001) and independently of cirrhosis in patients ≥ 60 years (p = 0.005). Furthermore, the hTERT promoter mutation was associated with cirrhosis caused by alcohol toxicity and hepatitis C virus infection. In noncirrhotic liver tissue, the frequency of hTERT-promoter-mutated HCC increased with the degree of inflammation and fibrosis. Nevertheless, 25% of the hTERT-promoter-mutated HCC developed in normal liver tissue without HCC risk factors. Multivariate Cox regression analysis did not reveal an influence of the hTERT promoter mutation in HCC on overall survival at 3, 5, and 16 years. Immunohistochemical analysis with the hTERT antibodies LS-B95 and 2D8 in hTERT-promoter-mutated HCC and hTERT-wildtype HCC showed a mildly stronger immunoreaction compared with the tumor-bearing liver tissue (LS-B95: p < 0.01, 2D8: p < 0.01).

Conclusions: Our study reveals a connection between pathological changes in tumor-bearing liver tissue and the hTERT promoter mutation in most HCC, even in noncirrhotic liver tissue. Immunohistochemical hTERT antibodies do not discriminate between hTERT-promoter-mutated and wildtype HCC.