title: Overexpression of the chemokine receptors CXCR4, CCR7, CCR9, and CCR10 in human primary cutaneous melanoma: a potential prognostic value for CCR7 and CCR10?
abstract: Multiple functional implications have been suggested for a limited number of chemokines and their cognate receptors in melanoma pathogenesis. The purpose of this study was to investigate the potential role of the chemokine receptors CXCR4, CCR7, CCR9, and CCR10 as prognostic markers in human primary cutaneous melanoma. Chemokine receptor expression was analyzed by immunohistochemistry in a total of 38 patients with cutaneous melanoma. Results were statistically correlated with melanoma features and clinical disease progression. No significant correlation between overexpression of CXCR4 or CCR9 and survival or prognosis was found. CCR7 overexpression was associated with significantly lower survival (0.005 log rank) and shorter time to progression (0.009 log rank)-similar to CCR10 overexpression (lower survival: 0.001 log rank, shorter time to progression: 0.002 log rank). In addition, CCR7 overexpression correlated with expression of metallothionein, while CCR10 seems to be associated with cerebral metastases. Two chemokine receptors permitting the identification of high-risk patients were identified: CCR7 and CCR10 overexpressions were found to be associated with a worse outcome of disease course independent of Breslow's tumor thickness and Clark level, thus representing possible additional prognostic markers.
authors.affiliation: Department of Dermatology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Laura
authors.initials: L
authors.lastname: Kühnelt-Leddihn
authors.forename: Hansgeorg
authors.initials: H
authors.lastname: Müller
authors.forename: Klaus
authors.initials: K
authors.lastname: Eisendle
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zelger
authors.forename: Georg
authors.initials: G
authors.lastname: Weinlich
mesh_terms: D015415:Biomarkers / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism*; D008668:Metallothionein / Q000096:biosynthesis; D011379:Prognosis; D054388:Receptors, CCR / Q000096:biosynthesis*; D054447:Receptors, CCR10 / Q000096:biosynthesis*; D054400:Receptors, CCR7 / Q000096:biosynthesis*; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D012720:Severity of Illness Index; D012878:Skin Neoplasms / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C119309:CC chemokine receptor 9; C515706:CCR10 protein, human; C515370:CCR7 protein, human; C527276:CXCR4 protein, human; D054388:Receptors, CCR; D054447:Receptors, CCR10; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D008668:Metallothionein