This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yurkovetsky, Z. R. Articles by Lokshin, A. E. Search for Related Content PubMed PubMed Citation Articles by Yurkovetsky, Z. R. Articles by Lokshin, A. E.

Multiplex Analysis of Serum Cytokines in Melanoma Patients Treated with Interferon-2b

Authors' Affiliations: ¹ University of Pittsburgh Cancer Institute; Departments of ² Medicine, ³ Surgery, ⁴ Pathology, and ⁵ Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Requests for reprints: Anna Lokshin, University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA 15213. Phone: 412-623-7706; Fax: 412-623-1415; E-mail: lokshina{at}pitt.edu.

Purpose: Interferon (IFN)-2b is the only Food and Drug Administration–approved treatment for operable high-risk melanoma that has been shown to significantly and durably prolong relapse-free survival (RFS) of patients with stage IIB-III melanoma. Development of reliable serum assays may contribute to the development of methods for earlier detection of melanoma and the selection of patients who may be most susceptible to current available interventions with IFN.

Experimental Design: A powerful high-throughput xMAP multiplex immunobead assay technology (Luminex Corp., Austin, TX) was used to simultaneously test 29 cytokines, chemokines, angiogenic as well as growth factors, and soluble receptors in the sera of 179 patients with high-risk melanoma and 378 healthy individuals.

Results: Serum concentrations of interleukin (IL)-1, IL-1ß, IL-6, IL-8, IL-12p40, IL-13, granulocyte colony-stimulating factor, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1, MIP-1ß, IFN, tumor necrosis factor (TNF)-, epidermal growth factor, vascular endothelial growth factor (VEGF), and TNF receptor II were found to be significantly higher in patients with resected high-risk melanoma compared with healthy controls. Bayesian Network algorithm classification of the data offered 90% sensitivity at 98% specificity with 96.5% of melanoma patients distinguished from healthy individuals. IFN-2b therapy resulted in a significant decrease of serum levels of immunosuppressive and tumor angiogenic/growth stimulatory factors (VEGF, epidermal growth factor, and hepatocyte growth factor) and increased levels of antiangiogenic IFN- inducible protein 10 (IP-10) and IFN-. Pretreatment levels of proinflammatory cytokines IL-1ß, IL-1, IL-6, TNF-, and chemokines MIP-1 and MIP-1ß were found to be significantly higher in the serum of patients with longer RFS values of 1 to 5 and >5 years when compared with patients with shorter RFS of <1 year.

Conclusion: These data show that multiplexed analysis of serum biomarkers is useful for the evaluation of prognostic markers of clinical outcome and potential predictive markers of response to IFN-2b in patients with high-risk operable melanoma.

This article has been cited by other articles:

				J. M. Kirkwood and A. A. Tarhini Biomarkers of Therapeutic Response in Melanoma and Renal Cell Carcinoma: Potential Inroads to Improved Immunotherapy J. Clin. Oncol., June 1, 2009; 27(16): 2583 - 2585. [Full Text] [PDF]

				S. Hu, C. C. Kim, C. Jessup, T. L. Phung, and C. Curiel-Lewandrowski Primary Cutaneous Melanomas Seen as Inflamed Pigmented Lesions in Patients Undergoing Adjuvant Interferon Treatment: A Possible Diagnostic Clue for Physicians Arch Dermatol, May 1, 2009; 145(5): 565 - 568. [Abstract] [Full Text] [PDF]

				J. MASHIAH, S. BRENNER, Y. PESSACH, V. BARAK, and J. SCHACHTER Differences in Cytokine Levels in Melanoma Patients with and without Redness (Brenner Sign) Anticancer Res, May 1, 2009; 29(5): 1793 - 1796. [Abstract] [Full Text] [PDF]

				J. VRZALOVA, M. PRAZAKOVA, Z. NOVOTNY, O. TOPOLCAN, M. CASOVA, and L. HOLUBEC JR. Test of Ovarian Cancer Multiplex xMAP Technology Panel Anticancer Res, February 1, 2009; 29(2): 573 - 576. [Abstract] [Full Text] [PDF]

				W. Wang, H. D. Edington, U. N.M. Rao, D. M. Jukic, A. Radfar, H. Wang, and J. M. Kirkwood Effects of High-Dose IFN{alpha}2b on Regional Lymph Node Metastases of Human Melanoma: Modulation of STAT5, FOXP3, and IL-17 Clin. Cancer Res., December 15, 2008; 14(24): 8314 - 8320. [Abstract] [Full Text] [PDF]