Prokineticins and Merkel cell polyomavirus infection in Merkel cell carcinoma.
BACKGROUND
Prokineticin-1 (PROK1) and prokineticin-2 (PROK2) are chemokine-like proteins that may influence cancer growth by regulating host defence and angiogenesis. Their significance in viral infection-associated cancer is incompletely understood. We studied prokineticins in Merkel cell carcinoma (MCC), a skin cancer linked with Merkel cell polyomavirus (MCPyV) infection.


METHODS
Carcinoma cell expression of PROK1 and PROK2 and their receptors (PROKR1 and PROKR2) was investigated with immunohistochemistry, and tumour PROK1 and PROK2 mRNA content with quantitative PCR from 98 MCCs. Subsets of tumour infiltrating leukocytes were identified using immunohistochemistry.


RESULTS
Merkel cell polyomavirus-positive MCCs had higher than the median PROK2 mRNA content, whereas MCPyV-negative MCCs contained frequently PROK1 mRNA. Cancers with high tumour PROK2 mRNA content had high counts of tumour infiltrating macrophages (CD68+ and CD163+ cells). Patients with higher than the median PROK2 mRNA content had 44.9% 5-year survival compared with 23.5% among those with a smaller content (hazard ratio (HR): 0.53; 95% confidence interval (CI): 0.34-0.84; P=0.005), whereas the presence of PROK1 mRNA in tumour was associated with unfavourable survival (P=0.052).


CONCLUSIONS
The results suggest that prokineticins are associated with MCPyV infection and participate in regulation of the immune response in MCC, and may influence outcome of MCC patients.
Laboratory of Molecular Oncology, Translational Cancer Biology Program, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.
S
S
Lauttia
Laboratory of Molecular Oncology, Translational Cancer Biology Program, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.
H
H
Sihto
Department of Plastic Surgery, Helsinki University Central Hospital, Topeliuksenkatu 5, 00029 Helsinki, Finland.
H
H
Kavola
Department of Plastic Surgery, Helsinki University Central Hospital, Topeliuksenkatu 5, 00029 Helsinki, Finland.
V
V
Koljonen
1] Department of Pathology, Haartman Institute, University of Helsinki, Haartmaninkatu 3C, 00029 Helsinki, Finland [2] HUSLAB, Helsinki University Central Hospital, Helsinki, Finland.
T
T
Böhling
1] Laboratory of Molecular Oncology, Translational Cancer Biology Program, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland [2] Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, Helsinki 00029, Finland.
H
H
Joensuu
D000328:Adult; D015266:Carcinoma, Merkel Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D005260:Female; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D027601:Polyomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D016019:Survival Analysis; D046888:Tissue Array Analysis; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000378:metabolism*
D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C467610:PROK1 protein, human; C423608:PROK2 protein, human; C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived