title: Wnt pathway activation predicts increased risk of tumor recurrence in patients with stage I nonsmall cell lung cancer.
abstract: OBJECTIVE
  To determine the incidence of Wnt pathway activation in patients with stage I NSCLC and its influence on lung cancer recurrence.
  
  
  BACKGROUND
  Despite resection, the 5-year recurrence with localized stage I nonsmall cell lung cancer (NSCLC) is 18.4%-24%. Aberrant Wnt signaling activation plays an important role in a wide variety of tumor types. However, there is not much known about the role the Wnt pathway plays in patients with stage I lung cancer.
  
  
  METHODS
  Tumor and normal lung tissues from 55 patients following resection for stage I NSCLC were subjected to glutathione S-transferase (GST) E-cadherin pulldown and immunoblot analysis to assess levels of uncomplexed β-catenin, a reliable measure of Wnt signaling activation. The β-catenin gene was also screened for oncogenic mutations in tumors with activated Wnt signaling. Cancer recurrence rates were correlated in a blinded manner in patients with Wnt pathway-positive and -negative tumors.
  
  
  RESULTS
  Tumors in 20 patients (36.4%) scored as Wnt positive, with only 1 exhibiting a β-catenin oncogenic mutation. Patients with Wnt-positive tumors experienced a significantly higher rate of overall cancer recurrence than those with Wnt-negative tumors (30.0% vs. 5.7%, P = 0.02), with 25.0% exhibiting distal tumor recurrence compared with 2.9% in the Wnt-negative group (P = 0.02).
  
  
  CONCLUSIONS
  Wnt pathway activation occurred in a substantial fraction of Stage I NSCLCs, which was rarely due to mutations. Moreover, Wnt pathway activation was associated with a significantly higher rate of tumor recurrence. These findings suggest that Wnt pathway activation reflects a more aggressive tumor phenotype and identifies patients who may benefit from more aggressive therapy in addition to resection.
authors.affiliation: Division of Thoracic Surgery, The Mount Sinai Medical Center, New York, NY 10029, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Shapiro
authors.forename: Gal
authors.initials: G
authors.lastname: Akiri
authors.forename: Cynthia
authors.initials: C
authors.lastname: Chin
authors.forename: Juan P
authors.initials: JP
authors.lastname: Wisnivesky
authors.forename: Mary B
authors.initials: MB
authors.lastname: Beasley
authors.forename: Todd S
authors.initials: TS
authors.lastname: Weiser
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Swanson
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Aaronson
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015994:Incidence; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics; D014481:United States / Q000453:epidemiology; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D051153:Wnt Proteins