title: Expression of CXCR4 predicts poor prognosis in patients with malignant melanoma.
abstract: OBJECTIVE
  CXCR4 receptor and its unique ligand, the CXCL12 chemokine, have been recently implicated in cancer metastasis. Evidence about the role of CXCR4/CXCL12 axis has been reported in several cancers including melanoma. Our goal was to investigate if CXCR4 expression has a prognostic value in malignant melanoma.
  
  
  METHODS
  Immunohistochemical expression of CXCR4 was evaluated on 71 specimens of primary cutaneous melanoma with a Breslow tumor thickness of >1 mm after radical resection. Associations between baseline patient features and tumors were analyzed by chi(2) test. The prognostic value of CXCR4 expression was evaluated by univariate and multivariate analyses adjusted by age, sex, Breslow tumor thickness, presence of ulceration, and sentinel lymph node metastases.
  
  
  RESULTS
  CXCR4 expression was detected in 31 of 71 (43.6%) primary cutaneous melanomas. Membrane or cytoplasmic staining for CXCR4 protein was absent in 56% of the tumors. The positive cases were divided into three score classes according to their staining: low in 15 cases (21%), moderate in 10 (14%), and high in 6 (8%). After a median follow-up of 38 months, 26 patients progressed (16 of 26 expressed CXCR4) and 19 died (12 of 19 expressed CXCR4). The CXCR4 expression on tumor cells was correlated with an unfavorable prognosis with a median disease-free and overall survival of 22 and 35 months, respectively. The hazard ratios of relapse and death, compared with patients with CXCR4-negative tumors, were 2.5 (95% confidence interval, 1.2-6.1) and 3.1 (95% confidence interval, 1.1-7.2), respectively. Median time-to-event (progression and survival) was not reached in patients with CXCR4-negative tumors. In the multivariate analysis, CXCR4 expression, presence of ulceration, and sentinel lymph node status emerged as independent prognostic factors.
  
  
  CONCLUSIONS
  This article provides the first evidence that CXCR4 expression could be an independent and powerful prognostic marker in primary cutaneous malignant melanomas.
authors.affiliation: Department of Clinical Immunology, National Cancer Institute, G. Pascale Foundation, via Mariano Semmola, 80131 Naples, Italy. ale.otto@libero.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Scala
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ottaiano
authors.forename: Paolo Antonio
authors.initials: PA
authors.lastname: Ascierto
authors.forename: Manuela
authors.initials: M
authors.lastname: Cavalli
authors.forename: Ester
authors.initials: E
authors.lastname: Simeone
authors.forename: Paola
authors.initials: P
authors.lastname: Giuliano
authors.forename: Maria
authors.initials: M
authors.lastname: Napolitano
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castello
mesh_terms: D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000032:analysis / Q000096:biosynthesis*; D012737:Sex Factors; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D019718:Receptors, CXCR4