CXCR3 chemokine receptor immunoreactivity in primary cutaneous malignant melanoma: correlation with clinicopathologic prognostic factors

¹ University of Valencia, Spain
² Hospital Clinico Universitario,Valencia, Spain

^* To whom correspondence should be addressed. E-mail: carlos.monteagudo{at}uv.es.

Accepted 13 October 2005

	Abstract

Aims: A role for CXCR3, the receptor for chemokines Mig, IP-10 and interferon-inducible T cell alpha-chemoattractant, in tumor cell migration during melanoma progression has been proposed. Our goal was to analyze CXCR3 expression in primary cutaneous malignant melanomas and its comparison with clinicopathologic and prognostic factors.

Methods: A retrospective immunohistochemical study was performed on formalin-fixed paraffin-embedded sections from 82 primary invasive cutaneous melanomas, with a monoclonal antibody to CXCR3 (clone 49801.111; R&D Systems). Immunoreactivity was semiquantitatively evaluated: labeling intensity (0 absent, 1 weak, 2 moderate, 3 strong) X percentage of cells in each of the four intensity categories. A positive staining was considered when the score was >100. Melanomas were categorized by age, sex, primary site, tumor thickness, growth phase, ulceration, lymphocytic infiltration, recurrence, lymph node and distant metastasis, and survival. Univariate and multivariate statistical analyses were performed.

Results: Of the 82 cases, a positive CXCR3 staining was found in 26 cases (31.7%), whereas 56 (68.3%) were negative. In univariate analysis, a statistically significant association of CXCR3-positive tumor cell immunostaining with tumor thickness >1mm (p=0.003), absent lymphocytic infiltration (p=0.04), and the presence of distant metastasis (p=0.048) was found. Multivariate analysis found tumor thickness as the only independent factor with significant association with distant metastases.

Conclusions: Our findings of a positive correlation of CXCR3 tumor cell immunoreactivity in human primary cutaneous melanoma with tumor thickness >1mm and absent intratumoral lymphocytic infiltration support the biological implication of CXCR3 in the tumor progression of cutaneous malignant melanoma.

Key Words: Chemokine Receptors, Cxcr3, Immunohistochemistry, Melanoma, Prognosis

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