title: Prognostic and predictive role of CXCR4, IGF-1R and Ezrin expression in localized synovial sarcoma: is chemotaxis important to tumor response?
abstract: BACKGROUND
  Synovial sarcoma (SS) is a rare tumor, with dismal survival when metastatic. The role of adjuvant chemotherapy is debated. New prognostic and predictive factors are needed.
  
  
  METHODS
  We reviewed patients with localized SS; SS18-SSX fusion transcript presence was confirmed by FISH and RT-PCR. Expression of CXCR4, IGF-1R and Ezrin were evaluated by immunohistochemistry.
  
  
  RESULTS
  Tumor samples from 88 SS patients (45 female; 43 male) with median age 37 years (range 11-63) were selected. The size of the lesion was > 5 cm in 68% of patients and 34% of cases presented biphasic histotype. All patients underwent surgery, 56% adjuvant radiotherapy (RT), 65% adjuvant chemotherapy. A positive stain for IGF-1R was detected in 55 patients, with nucleus expression in 21 patients. CXCR4 was expressed in 74 patients, nuclear pattern in 31 patients. 80 SS were positive to Ezrin, 48 had cytoplasmatic location, 32 membrane location. With a median follow-up of 6 years (1-30 years), the 5-year overall survival (OS) was 70% (95% CI 60-81). 5-year OS was 63% (95% CI 41-85%) for patients with positive IGF-1R/nuclear expression, and 73% (95% CI 61-85%; P = 0.05) in negative patients. 5-year OS was 47% (95% CI 27-66%) in patients with positive CXCR4/nuclear staining, and 86% (95% CI 76-96%, P = 0.0003) in negative cases. No survival difference was found according to Ezrin expression. By multivariate analysis, nuclear expression of CXCR4 and IGF-1R was confirmed independent adverse prognostic factor for SS patient survival linked to the use of chemotherapy.
  
  
  CONCLUSIONS
  Our findings have important potential implications demonstrating that together with clinical prognostic factors such as radiotherapy and age, CXCR4 and IGF-1R negatively influences survival in patients with localized SS. We believe that further studies addressed to the effects of CXCR4 and IGF-1R inhibitors on cell viability and function are needed to plan new and more appropriate SS treatments.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Palmerini
authors.forename: Maria Serena
authors.initials: MS
authors.lastname: Benassi
authors.forename: Irene
authors.initials: I
authors.lastname: Quattrini
authors.forename: Laura
authors.initials: L
authors.lastname: Pazzaglia
authors.forename: Davide
authors.initials: D
authors.lastname: Donati
authors.forename: Stefania
authors.initials: S
authors.lastname: Benini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gamberi
authors.forename: Marco
authors.initials: M
authors.lastname: Gambarotti
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002633:Chemotaxis; D002648:Child; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012334:RNA, Neoplasm; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D013584:Sarcoma, Synovial / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult; D000099149:Ezrin
chemical_list: D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D012334:RNA, Neoplasm; D017526:Receptor, IGF Type 1; D019718:Receptors, CXCR4; D000099149:Ezrin