title: Clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  CXCL-8, known as proinflammatory cytokine interleukin (IL)-8, and its receptor, CXCR-2, are expressed in various cancer cells. CXCL-8/CXCR-2 network is believed to be involved in angiogenesis, growth, and invasion of tumor cells. To date, the clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we investigated the role of CXCL- 8/CXCR-2 network in ESCC.
  
  
  METHODS
  The subjects included 78 patients with primary ESCC. We examined CXCL-8 and CXCR-2 expression in surgically resected specimens using immunohistochemistry. The association between CXCL-8/CXCR-2 expression and level of preoperative serum cytokines, C-reactive protein (CRP), coagulation factors, clinicopathologic background factors, and survival of ESCC patients was assessed.
  
  
  RESULTS
  Thirty-seven (47%) and 36 (46%) patients were positive for CXCL-8 and CXCR-2 expression, respectively. Both CXCL-8 and CXCR-2 were expressed in 26 patients (33%). We compared the results of these 26 patients [CXCL-8(+)/CXCR-2(+) group] with those of the other group (n = 52). The depth of invasion (pT factor; P < .001), lymph node metastasis (pN factor; P = .001), pathologic stage (P < .001), lymphatic invasion (P = .010), and venous invasion (P = .001) were significantly more advanced in the CXCL-8(+)/CXCR-2(+) group compared with the other group. Preoperative IL-6, IL-8, CRP, fibrin/fibrinogen degradation product, and fibrinogen levels in the CXCL-8(+)/CXCR-2(+) group were also significantly higher than those in the other group (P = .046, .009, .029, .010, and <.001, respectively). The CXCL-8(+)/CXCR-2(+) group also showed a significantly lower recurrence-free survival (RFS; P < .001) and disease-specific survival (P = .008). As per Cox's hazards model, CXCL-8/CXCR-2 expression (hazard ratio, 2.89; P = .008) was independent predictive factor for RFS.
  
  
  CONCLUSIONS
  Increased expression of both CXCL-8 and CXCR-2 correlated with tumor progression, metastasis, higher preoperative levels of proinflammatory cytokines, CRP, activation of exogenous coagulation factors, and poor prognosis in ESCC patients. These results indicate that overexpression of both CXCL-8 and CXCR-2 may be a useful marker for predicting the outcome in ESCC patients, and more important, has potential in becoming a critical diagnostic marker for selection of appropriate treatments.
authors: Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors: Masaharu
authors: M
authors: Ogura
authors: Hiroya
authors: H
authors: Takeuchi
authors: Hirofumi
authors: H
authors: Kawakubo
authors: Tomohiko
authors: T
authors: Nishi
authors: Kazumasa
authors: K
authors: Fukuda
authors: Rieko
authors: R
authors: Nakamura
authors: Tsunehiro
authors: T
authors: Takahashi
authors: Norihito
authors: N
authors: Wada
authors: Yoshiro
authors: Y
authors: Saikawa
authors: Tai
authors: T
authors: Omori
authors: Taku
authors: T
authors: Miyasho
authors: Shingo
authors: S
authors: Yamada
authors: Yuko
authors: Y
authors: Kitagawa
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000032:analysis / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D023063:Receptors, Interleukin-8B / Q000032:analysis / Q000502:physiology*
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B