title: Dysregulation of redox-state-regulating enzymes in melanocytic skin tumours and the surrounding microenvironment.
abstract: OBJECTIVE
  To investigate redox-regulating enzymes that may have a special role in melanoma pathogenesis due to continuous exposure to microenvironment-produced and ultraviolet radiation-induced oxidative stress.
  
  
  RESULTS
  We assessed immunohistochemically the expression of antioxidant enzymes peroxiredoxins (Prxs) I-IV, sulfiredoxin (Srx) and redox-regulated proto-oncogene DJ-1 in material consisting of 30 benign naevi, 14 lentigo malignas and 67 malignant melanomas. Evaluation of immunostaining was performed with special attention paid to protein expression in different tumour compartments. In particular, the expression patterns of nuclear Prx I and Prx II and cytoplasmic DJ-1 were decreased significantly in melanomas compared with dysplastic and benign naevi. In multivariate analysis, several prognostic factors were identified: Prx III expression in the cytoplasm of stromal fibroblasts was associated with shortened melanoma-specific survival [hazard ratio (HR) 6.730; 95% confidence interval (CI) 1.579-28.689], while cytoplasmic Prx IV expression in endothelial cells (HR 6.563; 95% CI 1.750-24.620) and Srx expression in the cytoplasm of keratinocytes (HR 6.988; 95% CI 1.559-31.324) were associated with better prognosis independently of ulceration, thickness of melanoma or its diagnostic type.
  
  
  CONCLUSIONS
  Redox-regulating enzymes have the potential to serve as novel prognostic factors and targeting them may offer new therapeutic options in malignant melanoma.
authors: Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, Kuopio, Finland.|Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.|University of Oulu and Department of Pathology, Oulu University Hospital, Oulu, Finland.|Department of Oncology and Radiotherapy, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors: Hanna-Riikka
authors: HR
authors: Hintsala
authors: Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, Kuopio, Finland.
authors: Ylermi
authors: Y
authors: Soini
authors: University of Oulu and Department of Pathology, Oulu University Hospital, Oulu, Finland.
authors: Kirsi-Maria
authors: KM
authors: Haapasaari
authors: Department of Oncology and Radiotherapy, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors: Peeter
authors: P
authors: Karihtala
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D018327:Hutchinson's Melanotic Freckle / Q000201:enzymology / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D009506:Nevus / Q000201:enzymology / Q000473:pathology; D009508:Nevus, Pigmented / Q000201:enzymology / Q000473:pathology; D015513:Oncogene Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism; D011379:Prognosis; D000071617:Protein Deglycase DJ-1; D000090063:Proto-Oncogene Mas; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D059016:Tumor Microenvironment; D000096142:Cutaneous Malignant Melanoma
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D054464:Peroxiredoxins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C504024:SRXN1 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1
keywords: DJ-1; melanoma; naevus; oxidative stress; peroxiredoxin; sulfiredoxin