title: Prognostic role of protease-activated receptors 1 and 4 in resected stage IB non-small-cell lung cancer.
abstract: BACKGROUND
  Protease-activated receptor (PAR)-1 and PAR-4 are involved in extracellular matrix invasion and angiogenesis.
  
  
  METHODS
  A series of 60 resected stage IB non-small-cell lung cancers (NSCLCs), including 30 adenocarcinomas (ADCs) and 30 squamous cell carcinomas (SCCs), were processed by immunohistochemistry with antibodies to PAR-1, PAR-4, vascular endothelial growth factor (VEGF), and CD34.
  
  
  RESULTS
  Protease-activated receptor-1 was expressed in 37 cases (62%) and PAR-4 in 39 (65%). Adenocarcinomas were significantly more positive than SCC for PAR-1 (17 vs. 8 cases) and PAR-4 (10 vs. 5 cases). Vascular endothelial growth factor was expressed in 42 cases (70%): 22 ADC and 20 SCC. A significant correlation emerged between PAR-1 and/or PAR-4 expression and VEGF but not with microvessel density. Median follow-up was 38 months; actuarial 5-year survival was 43%. At univariate analysis, 3-year survival was shorter in patients expressing PAR-4 versus negative cases (29% vs. 60%; P = 0.002). In 46 patients expressing PAR-1 and/or PAR-4, 3-year survival was 30% versus 68% in 14 patients with no PAR expression (P = 0.002). A trend toward shorter 3-year survival was seen in PAR-1-positive versus PAR-1-negative cases (34% vs. 46%; P = 0.06). Multivariate analysis identified expression of PAR-1 and/or PAR-4 as an independent prognostic factor for reduced survival in resected stage IB NSCLC.
  
  
  CONCLUSIONS
  Expression of PAR-1 and PAR-4 in early-stage NSCLC could be included in a molecular algorithm for the selection of patients eligible for adjuvant studies.
authors.affiliation: Division of Thoracic Oncology , University of Turin and San Luigi Hospital, Orbassano, Italy.
authors.forename: Paulo
authors.initials: P
authors.lastname: Ghio
authors.forename: Susanna
authors.initials: S
authors.lastname: Cappia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Selvaggi
authors.forename: Sylvia
authors.initials: S
authors.lastname: Novello
authors.forename: Paulo
authors.initials: P
authors.lastname: Lausi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Zecchina
authors.forename: Marno
authors.initials: M
authors.lastname: Papotti
authors.forename: Piero
authors.initials: P
authors.lastname: Borasio
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D044463:Receptor, PAR-1 / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D042461:Vascular Endothelial Growth Factor A