Fluorescence in situ hybridization and qPCR to detect Merkel cell polyomavirus physical status and load in Merkel cell carcinomas

被引:14
|
作者
Haugg, Anke M. [1 ]
Rennspiess, Dorit [1 ]
zur Hausen, Axel [1 ]
Speel, Ernst-Jan M. [1 ]
Cathomas, Gieri [2 ]
Becker, Juergen C. [3 ]
Schrama, David [3 ]
机构
[1] Maastricht UMC, GROW Sch Oncol & Dev Biol, Dept Pathol, Maastricht, Netherlands
[2] Kanton Inst Pathol, Liestal, Switzerland
[3] Med Univ Graz, Div Gen Dermatol, Dept Dermatol, Graz, Austria
关键词
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.
引用
收藏
页码:2804 / 2815
页数:12
相关论文
共 50 条
  • [1] Comprehensive Assessment of Merkel Cell Polyomavirus in Merkel Cell Carcinomas: Fluorescence in situ Hybridization Versus qPCR?
    Speel, E. M.
    Haugg, A.
    Rennspiess, D.
    zur Hausen, A.
    Cathomas, G.
    Becker, J.
    Schrama, D.
    JOURNAL OF MOLECULAR DIAGNOSTICS, 2012, 14 (06): : 677 - 677
  • [2] Fluorescence in situ hybridization versus qPCR as means to detect Merkel cell polyomavirus in Merkel cell carcinoma
    Haugg, Anke M.
    Rennspiess, Dorit
    zur Hausen, Axel
    Speel, Ernst-Jan M.
    Cathomas, Gieri
    Becker, Juergen C.
    Schrama, David
    CANCER RESEARCH, 2012, 72
  • [3] In situ hybridization assay for detection of Merkel cell polyomavirus in Merkel cell carcinoma
    Wang, C.
    Eid, M.
    Jiang, H.
    Hewitt, S.
    Brownell, I.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2020, 140 (07) : S15 - S15
  • [4] Presence of merkel cell polyomavirus in merkel cell carcinomas and small cell carcinomas
    Choi, Yoon-La
    Jung, Hun Soon
    Chung, Yeon Ju
    Park, Chan-Sik
    Park, Young Su
    Shin, Young Kee
    CANCER RESEARCH, 2009, 69
  • [5] Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas
    Varga, E.
    Kiss, M.
    Szabo, K.
    Kemeny, L.
    BRITISH JOURNAL OF DERMATOLOGY, 2009, 161 (04) : 930 - 932
  • [6] Frequent biological association of Merkel cell polyomavirus with Merkel cell carcinomas
    Speel, E. J.
    Schmidt, A.
    Baumann, M.
    Haesevoets, A.
    Diebold, J.
    Hofmann, P.
    Kurrer, M.
    Offner, F.
    Sauter, G.
    Cathomas, G.
    NEUROENDOCRINOLOGY, 2010, 92 (01) : 12 - 13
  • [7] Merkel cell polyomavirus is uncommon in New Zealand Merkel cell carcinomas
    Woodhouse, B.
    Robb, T. J.
    Hearn, J. I.
    Houseman, P. S.
    Hayward, G.
    Miller, R.
    Restall, A. P.
    Findlay, M.
    Lawrence, B.
    Print, C. G.
    Parker, K.
    Blenkiron, C.
    BRITISH JOURNAL OF DERMATOLOGY, 2018, 179 (05) : 1197 - 1198
  • [8] Detection of Merkel cell polyomavirus in Merkel cell carcinomas and small cell carcinomas by PCR and immunohistochemistry
    Jung, Hun Soon
    Choi, Yoon-La
    Choi, Jong-Sun
    Roh, Ji Hyeon
    Pyon, Jai-Kyong
    Woo, Kyong-Je
    Lee, Eun Hee
    Jang, Kee-Taek
    Han, Joungho
    Park, Chan-Sik
    Park, Young Soo
    Shin, Young Kee
    HISTOLOGY AND HISTOPATHOLOGY, 2011, 26 (10) : 1231 - 1241
  • [9] Detection of the Merkel cell polyomavirus in human Merkel cell carcinomas and the clinical implications of tumor viral status
    Doumani, R.
    Moshiri, A. S.
    Yelistratova, L.
    Chang, O.
    Delaney, M.
    Huang, M.
    McArdle, S.
    Nghiem, P.
    Blom, A.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2015, 135 : S44 - S44
  • [10] Merkel cell polyomavirus is implicated in a subset of Merkel cell carcinomas, in the Indian subcontinent
    Arora, Reety
    Rekhi, Bharat
    Chandrani, Pratik
    Krishna, Sudhir
    Dutt, Amit
    MICROBIAL PATHOGENESIS, 2019, 137