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01-07-2009 | Original Article

Prognostic significance of tumor iNOS and COX-2 in stage III malignant cutaneous melanoma

Authors: C. Christian Johansson, Suzanne Egyházi, Giuseppe Masucci, Helena Harlin, Dimitrios Mougiakakos, Isabel Poschke, Bo Nilsson, Liss Garberg, Rainer Tuominen, Diana Linden, Marianne Frostvik Stolt, Johan Hansson, Rolf Kiessling

Published in: Cancer Immunology, Immunotherapy | Issue 7/2009

Abstract

Purpose

New prognostic markers are needed for malignant melanoma. Inducible nitric oxide synthase (iNOS) and cyclooxygenase type 2 (COX-2) have been described to correlate with progression of melanoma. Moreover, activating mutations in BRAF/NRAS oncogenes are often detected in melanoma. The BRAF/NRAS mutation status and expression of COX-2 and iNOS were examined to compare their prognostic value for overall survival (OS) in stage III malignant cutaneous melanoma.

Experimental design

The expression of iNOS and COX-2 in metastatic lymph nodes from 21 rapidly progressing (OS from date of diagnosis of stage III disease ≤14 months) and 17 slowly progressing (OS ≥60 months) stage III cutaneous melanoma patients was examined by immunohistochemistry. The presence of BRAF/NRAS mutations was analyzed using direct DNA sequencing. χ² exact trend test and logistic regression analysis were used for statistical analysis.

Results

Both iNOS (P = 0.002) and COX-2 (P = 0.048) alone significantly predicted OS. The BRAF/NRAS mutation status did not significantly differ between patient groups, although iNOS significantly (P = 0.013) correlated with BRAF mutation frequency. Furthermore, the odds ratio (OR) with respect to OS of iNOS (OR = 10.4) was higher than that of COX-2 (OR = 5.6) and was stable in the multivariate analysis of OS together with disease stage IIIB/C, ulceration, number of metastatic lymph nodes, and Breslow tumor thickness.

Conclusion

Our data show that iNOS is an independent and stronger prognostic factor for OS in stage III malignant cutaneous melanoma than COX-2.

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Title: Prognostic significance of tumor iNOS and COX-2 in stage III malignant cutaneous melanoma
Authors: C. Christian Johansson
Suzanne Egyházi
Giuseppe Masucci
Helena Harlin
Dimitrios Mougiakakos
Isabel Poschke
Bo Nilsson
Liss Garberg
Rainer Tuominen
Diana Linden
Marianne Frostvik Stolt
Johan Hansson
Rolf Kiessling
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 7/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0631-1

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Abstract

Purpose

Experimental design

Results

Conclusion

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