Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression.
Merkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), a clinically and pathologically heterogeneous malignancy of dermal neuroendocrine cells. To investigate this heterogeneity, we developed a tissue microarray (TMA) to characterize immunohistochemical staining of candidate tumor cell proteins and a quantitative PCR assay to detect MCPyV and measure viral loads. MCPyV was detected in 19 of 23 (74%) primary MCC tumors, but 8 of these had less than 1 viral copy per 300 cells. Viral abundance of 0.06-1.2 viral copies/cell was directly related to presence of retinoblastoma gene product (pRb) and terminal deoxyribonucleotidyl transferase (TdT) by immunohistochemical staining (p < or = 0.003). Higher viral abundance tumors tended to be associated with less p53 expression, younger age at diagnosis and longer survival (p < or = 0.08). These data suggest that MCC may arise through different oncogenic pathways, including ones independent of pRb and MCPyV.
Bhatia
Kishor
K
Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. bhatiak@mail.nih.gov
Goedert
James J
JJ
Modali
Rama
R
Preiss
Liliana
L
Ayers
Leona W
LW
D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000145:classification / Q000235:genetics / Q000821:virology*; D004253:DNA Nucleotidylexotransferase / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018862:Merkel Cells / Q000821:virology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011120:Polyomavirus / Q000235:genetics / Q000302:isolation & purification*; D016160:Retinoblastoma Protein / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D004279:DNA, Viral; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D004253:DNA Nucleotidylexotransferase