Volume 67, Issue 3 pp. 348-357
Original Article

Dysregulation of redox-state-regulating enzymes in melanocytic skin tumours and the surrounding microenvironment

Hanna-Riikka Hintsala

Hanna-Riikka Hintsala

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

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Ylermi Soini

Ylermi Soini

Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, Kuopio, Finland

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Kirsi-Maria Haapasaari

Kirsi-Maria Haapasaari

University of Oulu and Department of Pathology, Oulu University Hospital, Oulu, Finland

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Peeter Karihtala

Corresponding Author

Peeter Karihtala

Department of Oncology and Radiotherapy, Oulu University Hospital and University of Oulu, Oulu, Finland

Address for correspondence: P Karihtala, Department of Oncology and Radiotherapy, Oulu University Hospital, PO Box 22, 90029 Oulu, Finland. e-mail: [email protected]Search for more papers by this author
First published: 27 January 2015
Citations: 16

Abstract

Aims

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.

Methods and 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.

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