Merkel cell carcinoma;
Merkel cell polyomavirus;
carcinogenesis;
viral integration;
viral load;
fluorescence in situ hybridization;
HUMAN PAPILLOMAVIRUS TYPE-16;
RISK HUMAN-PAPILLOMAVIRUS;
LARGE T-ANTIGEN;
CERVICAL-CANCER;
MESOTHELIAL CELLS;
INTEGRATION;
EXPRESSION;
DNA;
INFECTION;
VIRUS;
D O I:
10.1002/ijc.28931
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
The Merkel cell polyomavirus (MCPyV) is detected in 80% of Merkel cell carcinomas (MCC). Clonal integration and tumor-specific mutations in the large T antigen are strong arguments that MCPyV is a human tumor virus. However, the relationship between viral presence and cancer induction remains discussed controversially. Since almost all studies on virus prevalence are based on PCR techniques, we performed MCPyV fluorescence in situ hybridization (FISH) on MCC to gain information about the quality of the viral presence on the single cell level. MCPyV-FISH was performed on tissue microarrays containing 62 formalin-fixed and paraffin-embedded tissue samples including all tumor grades of 42 patients. The hybridization patterns were correlated to the qPCR data determined on corresponding whole tissue sections. Indeed, MCPyV-FISH and qPCR data were highly correlated, i.e. 83% for FISH-positive and 93% for FISH-negative cores. Accordingly, the mean of the qPCR values of all MCPyV-positive cores differed significantly from the mean of the negative cores (p = 0.0076). Importantly, two hybridization patterns were definable in the MCPyV-FISH: a punctate pattern (85%) indicating viral integration, which correlated with a moderate viral abundance and a combination of the punctate with a diffuse pattern (15%), suggesting a possible coexistence of integrated and episomal virus which was associated with very high viral load and VP1 expression. Thus, MCPyV-FISH adds important information on the single cell level within the histomorphological context and could therefore be an important tool to further elucidate MCPyV related carcinogenesis.
机构:
Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Univ Auckland, Fac Med & Hlth Sci, Discipline Oncol, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Woodhouse, B.
Robb, T. J.
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Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Robb, T. J.
Hearn, J. I.
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Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Hearn, J. I.
Houseman, P. S.
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Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Houseman, P. S.
Hayward, G.
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Waitemata Dist Hlth Board, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Hayward, G.
Miller, R.
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Auckland Dist Hlth Board, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Miller, R.
Restall, A. P.
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Auckland Dist Hlth Board, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Restall, A. P.
Findlay, M.
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Univ Auckland, Fac Med & Hlth Sci, Discipline Oncol, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Findlay, M.
Lawrence, B.
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Univ Auckland, Fac Med & Hlth Sci, Discipline Oncol, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Lawrence, B.
Print, C. G.
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Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Print, C. G.
Parker, K.
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Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Univ Auckland, Fac Med & Hlth Sci, Discipline Oncol, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Parker, K.
Blenkiron, C.
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Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
Univ Auckland, Fac Med & Hlth Sci, Dept Obstet & Gynaecol, Auckland, New ZealandUniv Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
机构:Seoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South Korea
Jung, Hun Soon
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Choi, Yoon-La
Choi, Jong-Sun
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Dongguk Univ Seoul, Grad Sch Med, Dept Pathol, Seoul, South KoreaSeoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South Korea
Choi, Jong-Sun
Roh, Ji Hyeon
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Dongguk Univ Seoul, Grad Sch Med, Dept Pathol, Seoul, South KoreaSeoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South Korea
Roh, Ji Hyeon
Pyon, Jai-Kyong
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机构:
Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Plast Surg, Seoul, South KoreaSeoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South Korea
Pyon, Jai-Kyong
Woo, Kyong-Je
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Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Plast Surg, Seoul, South KoreaSeoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South Korea
Woo, Kyong-Je
Lee, Eun Hee
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Sungkyunkwan Univ, Sch Med, Samsung Changwon Hosp, Dept Pathol, Chang Won, South KoreaSeoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South Korea
Lee, Eun Hee
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机构:
Jang, Kee-Taek
Han, Joungho
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h-index: 0
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Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South KoreaSeoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South Korea
Han, Joungho
Park, Chan-Sik
论文数: 0引用数: 0
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Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South KoreaSeoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South Korea
Park, Chan-Sik
Park, Young Soo
论文数: 0引用数: 0
h-index: 0
机构:
Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South KoreaSeoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South Korea
Park, Young Soo
Shin, Young Kee
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Seoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South KoreaSeoul Natl Univ, Coll Pharm, Dept Pharm, Mol Pathol Lab,Res Inst Pharmaceut Sci, Seoul 151742, South Korea