title: CD147 overexpression allows an accurate discrimination of bladder cancer patients' prognosis.
abstract: BACKGROUND
  Urothelial bladder carcinoma (UBC) is a chemo-sensitive tumour, but the response to treatment is heterogeneous. CD147 has been associated with chemotherapy resistance. We aimed to define tumours with an aggressive phenotype by the combined analysis of clinicopathological and biological parameters.
  
  
  METHODS
  77 patients with T1G3 or muscle-invasive UBC treated by radical cystectomy were studied. Immunohistochemistry was performed to detect CD147, heparanase, CD31 (blood vessels identification) and D2-40 (lymphatic vessels identification) expressions. The immunohistochemical reactions were correlated with the clinicopathological and the outcome parameters. 5-year disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. Multivariate analysis was performed by Cox proportional hazards analysis.
  
  
  RESULTS
  The 5-year DFS and OS rates were significantly influenced by the classical clinicopathological parameters, and by the occurrence of lymphovascular invasion. CD147 and heparanase immunoexpression did not affect patients' outcome. However, patients with pT3/pT4 tumours had a median OS time of 14.7 months (95% CI 7.1-22.3, p = 0.003), which was reduced to 9.2 months (95% CI 1.5-17.0, p = 0.008) if the tumours were CD147 positive. We developed a model of tumour aggressiveness using parameters as stage, grade, lymphovascular invasion and CD147 immunoexpression, which separated a low aggressiveness from a high aggressiveness group, remaining as an independent prognostic factor of DFS (HR 3.746; 95% CI 1.244-11.285; p = 0.019) and OS (HR 3.247; 95% CI 1.015-10.388, p = 0.047).
  
  
  CONCLUSIONS
  CD147 overexpression, included in a model of UBC aggressiveness, may help surgeons to identify patients who could benefit from a personalized therapeutic regimen. Additional validation is needed.
authors: Life and Health Sciences Research Institute - ICVS, School of Health Sciences, University of Minho, Braga, Portugal.
authors: J
authors: J
authors: Afonso
authors: A
authors: A
authors: Longatto-Filho
authors: F
authors: F
authors: Baltazar
authors: N
authors: N
authors: Sousa
authors: F E
authors: FE
authors: Costa
authors: A
authors: A
authors: Morais
authors: T
authors: T
authors: Amaro
authors: C
authors: C
authors: Lopes
authors: L L
authors: LL
authors: Santos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051926:Basigin / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000099175:Heparanase
chemical_list: D051926:Basigin; D014408:Biomarkers, Tumor; D005966:Glucuronidase; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000099175:Heparanase