title: Aberrant Wnt1/β-catenin expression is an independent poor prognostic marker of non-small cell lung cancer after surgery.
abstract: BACKGROUND
  The Wnt signaling pathway plays a major role in cancer development and progression. As a novel anticancer drug can be developed using inhibitors of this pathway, we investigated the clinical significance of the Wnt signaling pathway molecules in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Immunohistochemical analysis of a tissue microarray with 262 resected NSCLC specimens was performed to study the expression and subcellular localization of Wnt1 in relation to downstream molecules, including GSK-3β, β-catenin, c-Myc, cyclin D1, and p53. These results were correlated with other clinicopathologic features.
  
  
  RESULTS
  Cytoplasmic Wnt1 overexpression was detected in 36.6% (96 of 262) NSCLCs, and aberrant β-catenin staining was identified in 76% (189 of 262) of NSCLCs. There were significant associations between Wnt1 expression and altered expression of β-catenin (p = 0.034), overexpression of c-Myc (p < 0.001), or overexpression of cyclin D1 (p = 0.018). While there was no significant association between Wnt1 or β-catenin and stage, the 5-year survival was significantly lower in patients with Wnt1- and β-catenin-positive NSCLCs than negative NSCLCs (p < 0.05, respectively). In multivariate analysis, stage and Wnt1+/β-catenin+ expression were independent prognostic factors of overall survival (p < 0.05).
  
  
  CONCLUSIONS
  These findings show that Wnt1 expression may be one of the possible mechanisms of the activation of the canonical Wnt/β-catenin signaling pathway in NSCLC, and Wnt1 and altered β-catenin expression are poor prognostic markers, independent of stage.
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Xu
authors.forename: Ping-Li
authors.initials: PL
authors.lastname: Sun
authors.forename: Jun-Zhe
authors.initials: JZ
authors.lastname: Li
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Jheon
authors.forename: Choon-Taek
authors.initials: CT
authors.lastname: Lee
authors.forename: Jin-Haeng
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015996:Survival Rate; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051155:Wnt1 Protein / Q000378:metabolism*; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C530104:CCND1 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C495247:WNT1 protein, human; D051155:Wnt1 Protein; D051176:beta Catenin; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3