title: High CXCR4 expression correlates with sunitinib poor response in metastatic renal cancer.
abstract: BACKGROUND
  Almost 30% of the sunitinib-treated patients for metastatic renal carcinoma (mRCC) do not receive a clinical benefit. Convincing evidences demonstrated a cross talk between the VEGF and CXCR4 pathways. It was hypothesized that CXCR4 expression in primary renal cancer could predict sunitinib responsiveness.
  
  
  METHODS
  In this exploratory study sixty-two mRCC patients receiving sunitinib as first-line treatment were evaluated for CXCR4 expression through immunohistochemistry (IHC). Correlations between CXCR4 expression, baseline patients and tumour characteristics were studied by contingency tables and the chi-square test. Univariable analysis was performed with the log-rank test, and the Cox model was applied for multivariable analysis.
  
  
  RESULTS
  The objective response rate of sunitinib first-line therapy was 35.5% (22/62) with a disease control rate (response and stable disease) of 62.9% (39/62). CXCR4 expression was absent/low in 30 (48.4%), moderate in 17 (27.4%), and high in 15 (24.2%) tumors respectively. Low or absent CXCR4 expression predicted response to sunitinib therapy. Moreover, Fuhrman grading and concomitant, CXCR4 and Fuhrman grading, strongly predicted sunitinib first line therapy responsiveness on progression-free survival and overall survival.
  
  
  CONCLUSIONS
  High CXCR4 expression correlates with sunitinib poor response in metastatic renal cancer.
authors.affiliation: Department of Oncological Immunology, Istituto per lo Studio e la Cura dei Tumori "Pascale", Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: D' Alterio
authors.forename: L
authors.initials: L
authors.lastname: Portella
authors.forename: A
authors.initials: A
authors.lastname: Ottaiano
authors.forename: M
authors.initials: M
authors.lastname: Rizzo
authors.forename: G
authors.initials: G
authors.lastname: Carteni
authors.forename: S
authors.initials: S
authors.lastname: Pignata
authors.forename: G
authors.initials: G
authors.lastname: Facchini
authors.forename: S
authors.initials: S
authors.lastname: Perdona
authors.forename: G
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: R
authors.initials: R
authors.lastname: Autorino
authors.forename: R
authors.initials: R
authors.lastname: Franco
authors.forename: A
authors.initials: A
authors.lastname: La Mura
authors.forename: O
authors.initials: O
authors.lastname: Nappi
authors.forename: G
authors.initials: G
authors.lastname: Castello
authors.forename: S
authors.initials: S
authors.lastname: Scala
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000627:therapeutic use*; D007558:Italy; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D012307:Risk Factors; D000077210:Sunitinib; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D007211:Indoles; D011758:Pyrroles; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D000077210:Sunitinib