High Prevalence of Human Polyomavirus 7 in Cholangiocarcinomas and Adjacent Peritumoral Hepatocytes: Preliminary Findings
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Specimens
2.2. Degenerated PCR
2.3. Specific HPyVs DNA PCR
2.4. Fluorescence In Situ Hybridization (FISH)
2.5. RNA In Situ Hybridization (RISH)
2.6. Immunohistochemistry (IHC)
2.7. Statistical Analysis
3. Results
3.1. Histopathology and Specimen Quality
3.2. Screening for Human Polyomaviruses Using Degenerate and HPyVs-Specific PCR
3.3. Fluorescence In Situ Hybridization (FISH)
3.4. RNA In Situ Hybridization (RISH)
3.5. Detection of HPyV7-sTAg, HPyV6-sTAg, and MCPyV-LTag Expression by Immunohistochemistry
3.6. Overall Survival Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Patient ID. | Gender | Age | Diagnosis | Clinical Stage | Degenerated PCR | HPyV7 | HPyV6 | MCPyV | Result | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|
LTAg | sTAg | sTAg | M1/M2 | VP1 | LT3 | |||||||
CCA1 | F | 67 | iCCA | II | HPyV7 | + | + | − | + | + | + | HPyV7/MCPyV |
CCA2 | M | 59 | iCCA | II | − | − | − | + | − | − | − | HPyV6 |
CCA3 | F | 68 | iCCA | I | − | − | − | − | − | − | − | − |
CCA4 | F | 29 | iCCA | III | − | − | − | + | − | − | − | HPyV6 |
CCA6 | M | 74 | iCCA | I | MCPyV | + | + | − | − | − | − | HPyV7/MCPyV |
CCA7 | M | 64 | pCCA | I | MCPyV | − | − | − | − | − | + | MCPyV |
CCA8 | F | 64 | pCCA | III | HPyV7 | + | − | − | − | − | − | HPyV7 |
CCA9 | M | 45 | pCCA | I | MCPyV | − | − | − | + | − | − | MCPyV |
CCA11 | F | 50 | dCCA | II | HPyV7 | + | − | − | − | − | − | HPyV7 |
CCA12 | M | 70 | iCCA | II | HPyV7 | + | + | − | − | − | − | HPyV7 |
CCA13 | M | 69 | iCCA | I | HPyV7 | + | − | − | − | − | − | HPyV7 |
CCA14 | M | 70 | iCCA | I | HPyV7 | + | + | − | − | − | − | HPyV7 |
CCA15 | F | 71 | iCCA | I | HPyV7 | + | − | + | − | − | − | HPyV6/HPyV7 |
CCA16 | F | 64 | iCCA | II | − | − | − | − | − | − | − | − |
CCA17 | M | 59 | pCCA | III | HPyV7 | + | − | − | − | − | − | HPyV7 |
CCA19 | M | 69 | iCCA | I | HPyV7 | + | + | − | + | − | + | HPyV7/MCPyV |
CCA20 | M | 71 | iCCA | II | HPyV7 | + | + | − | − | − | − | HPyV7 |
CCA21 | F | 63 | iCCA | III | HPyV7 | + | − | − | − | − | − | HPyV7 |
CCA22 | M | 61 | iCCA | I | HPyV7 | + | − | − | − | − | − | HPyV7 |
CCA23 | M | 63 | iCCA | I | NA | + | − | − | − | − | − | HPyV7 |
CCA24 | M | 73 | iCCA | I | NA | + | − | − | + | − | − | MCPyV/HPyV7 |
CCA25 | F | 74 | iCCA | II | NA | − | − | + | − | − | − | HPyV6 |
CCA26 | F | 60 | iCCA | II | NA | + | + | − | − | − | − | HPyV7 |
CCA27 | M | 75 | iCCA | I | NA | + | − | − | + | − | − | MCPyV/HPyV7 |
CCA28 | M | 50 | pCCA | I | NA | + | − | − | − | − | − | HPyV7 |
CCA29 | F | 45 | iCCA | I | NA | − | − | − | − | − | − | − |
CCA30 | F | 66 | pCCA | I | NA | − | + | − | − | − | − | HPyV7 |
CCA31 | F | 74 | iCCA | III | NA | + | + | − | − | − | − | HPyV7 |
CCA32 | F | 77 | iCCA | I | NA | + | − | − | + | − | − | MCPyV/HPyV7 |
CCA33 | M | 77 | iCCA | IV | NA | + | − | − | − | + | − | MCPyV/HPyV7 |
CCA34 | M | 77 | pCCA | I | NA | − | − | + | − | − | − | HPyV6 |
CCA35 | M | 59 | pCCA | IV | NA | − | + | − | − | − | − | HPyV7 |
CCA36 | M | 72 | pCCA | II | NA | + | − | − | − | − | − | HPyV7 |
CCA37 | M | 60 | iCCA | I | NA | − | + | + | − | − | − | HPyV7/HPyV6 |
CCA38 | F | 85 | iCCA | I | NA | − | − | − | − | − | − | − |
CCA39 | M | 52 | iCCA | II | NA | + | − | − | − | − | − | HPyV7 |
CCA40 | M | 63 | iCCA | II | NA | − | − | − | − | − | − | − |
CCA41 | M | 78 | pCCA | I | NA | − | − | − | − | − | − | − |
CCA42 | F | 72 | iCCA | I | NA | + | − | − | − | − | − | HPyV7 |
CCA43 | F | 74 | iCCA | I | NA | + | − | − | + | − | − | MCPyV/HPyV7 |
CCA44 | M | 60 | iCCA | III | NA | − | − | − | − | − | − | − |
CCA45 | M | 66 | pCCA | I | NA | + | − | − | − | − | − | HPyV7 |
Results | F:17 M:25 | iCCA:30 pCCA:11 dCCA:1 | HPyV7:12 MCPyV:3 | 26/42 | 11/42 | 6/42 | 7/42 | 2/42 | 3/42 | HPyV7:29 HPyV6: 6 MCPyV:10 |
Patient ID | HPyV7 | HPyV6 | MCPyV | Result | ||||||
---|---|---|---|---|---|---|---|---|---|---|
FISH | IHC | FISH | RNA-Ish | IHC | FISH | IHC | ||||
Hepatocyte | Bile Duct Epithelium | CCA | ||||||||
CCA1 | ++ | +++ | ++ | ++ | − | NA | +++ | + | + | HPyV7 MCPyV |
CCA2 | − | − | − | − | + | + | ++ | − | NA | HPyV6 |
CCA4 | − | NA | NA | NA | + | NA | +++ | NA | NA | HPyV6 |
CCA6 | − | + | ++ | − | − | NA | ++ | + | ++ | HPyV7 MCPyV |
CCA7 | NA | − | − | − | − | − | +++ | ++ | +++ | MCPyV |
CCA8 | − | + | + | +++ | − | − | ++ | NA | NA | HPyV7 |
CCA9 | − | − | − | − | − | NA | +++ | − | ++ | MCPyV |
CCA11 | − | ++ | ++ | +++ | − | NA | NA | NA | − | HPyV7 |
CCA12 | − | + | ++ | + | − | NA | NA | NA | NA | HPyV7 |
CCA13 | NA | − | − | + | NA | NA | NA | NA | NA | HPyV7 |
CCA14 | + | +++ | + | − | NA | − | +++ | NA | NA | HPyV7 |
CCA15 | + | +++ | + | +++ | ++ | + | +++ | NA | NA | HPyV6 HPyV7 |
CCA16 | NA | − | − | − | NA | NA | − | − | NA | − |
CCA17 | NA | + | + | − | NA | NA | + | NA | NA | HPyV7 |
CCA19 | NA | + | + | + | NA | NA | − | + | + | HPyV7 MCPyV |
CCA20 | NA | + | + | + | NA | NA | + | NA | NA | HPyV7 |
CCA21 | + | + | + | + | − | NA | + | NA | NA | HPyV7 |
Total | 4/11 | 11/16 | 11/16 | 9/16 | 3/11 | 2/5 | 12/14 | 4/7 | 5/6 |
Variable | Hazards Ratio | p-Value |
---|---|---|
Sex | 0.617888 | 0.521 |
Age | 1.004683 | 0.893 |
Subtype | 2.639623 | 0.174 |
Stage | 0.761135 | 0.551 |
HPyV7 | 0.741641 | 0.726 |
HPyV6 | 2.293245 | 0.366 |
MCPyV | 1.057001 | 0.953 |
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Klufah, F.; Mobaraki, G.; Chteinberg, E.; Alharbi, R.A.; Winnepenninckx, V.; Speel, E.J.M.; Rennspiess, D.; Olde Damink, S.W.; Neumann, U.P.; Kurz, A.K.; et al. High Prevalence of Human Polyomavirus 7 in Cholangiocarcinomas and Adjacent Peritumoral Hepatocytes: Preliminary Findings. Microorganisms 2020, 8, 1125. https://doi.org/10.3390/microorganisms8081125
Klufah F, Mobaraki G, Chteinberg E, Alharbi RA, Winnepenninckx V, Speel EJM, Rennspiess D, Olde Damink SW, Neumann UP, Kurz AK, et al. High Prevalence of Human Polyomavirus 7 in Cholangiocarcinomas and Adjacent Peritumoral Hepatocytes: Preliminary Findings. Microorganisms. 2020; 8(8):1125. https://doi.org/10.3390/microorganisms8081125
Chicago/Turabian StyleKlufah, Faisal, Ghalib Mobaraki, Emil Chteinberg, Raed A. Alharbi, Véronique Winnepenninckx, Ernst Jan M. Speel, Dorit Rennspiess, Steven W. Olde Damink, Ulf P. Neumann, Anna Kordelia Kurz, and et al. 2020. "High Prevalence of Human Polyomavirus 7 in Cholangiocarcinomas and Adjacent Peritumoral Hepatocytes: Preliminary Findings" Microorganisms 8, no. 8: 1125. https://doi.org/10.3390/microorganisms8081125