High Prevalence of Human Polyomavirus 7 in Cholangiocarcinomas and Adjacent Peritumoral Hepatocytes: Preliminary Findings

Microorganisms, vol. 8, pp. 1125

Abstract

Cholangiocarcinoma (CCA) is a rare biliary-duct malignancy with poor prognosis. Recently, the presence of the human polyomavirus 6 (HPyV6) has been reported in the bile of diverse hepatobiliary diseases, particularly in the bile of CCA patients. Here, we investigated the presence of novel HPyVs in CCA tissues using diverse molecular techniques to assess a possible role of HPyVs in CCA. Formalin-Fixed Paraffin-Embedded (FFPE) tissues of 42 CCA patients were included in this study. PCR-based screening for HPyVs was conducted using degenerated and HPyV-specific primers. Following that, we performed FISH, RNA in situ hybridization (RNA-ISH), and immunohistochemistry (IHC) to assess the presence of HPyVs in selected tissues. Of all 42 CCAs, 25 (59%) were positive for one HPyV, while 10 (24%) CCAs were positive for 2 HPyVs simultaneously, and 7 (17%) were negative for HPyVs. Of the total 35 positive CCAs, 19 (45%) were positive for HPyV7, 4 (9%) for HPyV6, 2 (5%) for Merkel cell polyomavirus (MCPyV), 8 (19%) for both HPyV7/MCPyV, and 2 (5%) for both HPyV6/HPyV7 as confirmed by sequencing. The presence of viral nucleic acids was confirmed by specific FISH, while the RNA-ISH confirmed the presence of HPyV6 on the single-cell level. In addition, expression of HPyV7, HPyV6, and MCPyV proteins were confirmed by IHC. Our results strongly indicate that HPyV7, HPyV6, and MCPyV infect bile duct epithelium, hepatocytes, and CCA cells, which possibly suggest an indirect role of these viruses in the etiopathogenesis of CCA. Furthermore, the observed hepatotropism of these novel HPyV, in particular HPyV7, might implicate a role of these viruses in other hepatobiliary diseases.

Authors 12

1. Faisal Klufah

   Maastricht University · Maastricht University Medical Centre

   Affiliation as printed

   Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Albaha 65779, Saudi Arabia

   Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University, Medical Centre+, 6229 HX Maastricht, The Netherlands

2. Ghalib Mobaraki

   Maastricht University · Maastricht University Medical Centre · Jazan University

   Affiliation as printed

   Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia

   Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University, Medical Centre+, 6229 HX Maastricht, The Netherlands

3. Emil Chteinberg

   Maastricht University · Maastricht University Medical Centre

   Affiliation as printed

   Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University, Medical Centre+, 6229 HX Maastricht, The Netherlands

4. Raed Alharbi
   Affiliation as printed

   Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Albaha 65779, Saudi Arabia

5. Veronique J.L. Winnepenninckx

   Maastricht University · Maastricht University Medical Centre

   Affiliation as printed

   Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University, Medical Centre+, 6229 HX Maastricht, The Netherlands

6. Ernst‐Jan M. Speel

   Maastricht University · Maastricht University Medical Centre

   Affiliation as printed

   Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University, Medical Centre+, 6229 HX Maastricht, The Netherlands

7. Dorit Rennspiess

   Maastricht University · Maastricht University Medical Centre

   Affiliation as printed

   Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University, Medical Centre+, 6229 HX Maastricht, The Netherlands

8. Steven W.M. Olde Damink Aachen Department of General, Visceral and Transplantation Surgery

   RWTH Aachen University · Universitätsklinikum Aachen · Maastricht University

   Affiliation as printed

   Department of General Visceral and Transplantation Surgery, RWTH University Hospital Aachen, 52074 Aachen, Germany

   Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands

9. Ulf P. Neumann Aachen Department of General, Visceral and Transplantation Surgery

   RWTH Aachen University · Universitätsklinikum Aachen · Maastricht University

   Affiliation as printed

   Department of General Visceral and Transplantation Surgery, RWTH University Hospital Aachen, 52074 Aachen, Germany

   Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands

10. Anna Kordelia Kurz Aachen Department of Internal Medicine IV

    RWTH Aachen University · Universitätsklinikum Aachen

    Affiliation as printed

    Department of Internal Medicine IV, RWTH Aachen University Hospital, 52074 Aachen, Germany

11. Iryna V. Samarska

    Maastricht University · Maastricht University Medical Centre

    Affiliation as printed

    Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University, Medical Centre+, 6229 HX Maastricht, The Netherlands

12. Axel zur Hausen corresponding

    Maastricht University · Maastricht University Medical Centre

    Affiliation as printed

    Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University, Medical Centre+, 6229 HX Maastricht, The Netherlands