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

被引：46

作者：

Johansson, C. Christian ^{[1
]}

Egyhazi, Suzanne ^{[1
]}

Masucci, Giuseppe ^{[1
]}

Harlin, Helena ^{[1
]}

Mougiakakos, Dimitrios ^{[1
]}

Poschke, Isabel ^{[1
]}

Nilsson, Bo ^{[1
]}

Garberg, Liss ^{[1
]}

Tuominen, Rainer ^{[1
]}

Linden, Diana ^{[1
]}

Stolt, Marianne Frostvik ^{[1
]}

Hansson, Johan ^{[1
]}

Kiessling, Rolf ^{[1
]}

机构：

[1] Karolinska Univ Hosp, Dept Pathol & Oncol, Canc Ctr Karolinska, Karolinska Inst, S-17176 Stockholm, Sweden

来源：

CANCER IMMUNOLOGY IMMUNOTHERAPY | 2009年 / 58卷 / 07期

关键词：

iNOS; COX-2; Metastatic lymph node; Stage III melanoma; Survival; Prognostic factor; NITRIC-OXIDE SYNTHASE; AMERICAN JOINT COMMITTEE; POOR SURVIVAL; CELL-LINES; L-ARGININE; CANCER; CYCLOOXYGENASE-2; EXPRESSION; MUTATIONS; BRAF;

D O I：

10.1007/s00262-008-0631-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. The expression of iNOS and COX-2 in metastatic lymph nodes from 21 rapidly progressing (OS from date of diagnosis of stage III disease a parts per thousand currency sign14 months) and 17 slowly progressing (OS a parts per thousand yen60 months) stage III cutaneous melanoma patients was examined by immunohistochemistry. The presence of BRAF/NRAS mutations was analyzed using direct DNA sequencing. chi(2) exact trend test and logistic regression analysis were used for statistical analysis. 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. Our data show that iNOS is an independent and stronger prognostic factor for OS in stage III malignant cutaneous melanoma than COX-2.

引用

页码：1085 / 1094

页数：10

共 45 条

[1] BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival [J].