title: Keratin 34betaE12/keratin7 expression is a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer.
abstract: BACKGROUND
  Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7) and keratin 34βE12 expression by immunohistochemistry and validated in a comparable independent Norwegian cohort of 276 stage I-IIIA NSCLC patients.
  
  
  RESULTS
  Based on keratin 34βE12/K7 expression, three subgroups with significantly different median cancer-specific survival rates were identified (34βE12+/K7+, 168 months vs. 34βE12+/K7+, 73 months vs. 34βE12-/K7+, 30 months; p = 0.0004). In multivariate analysis, stage II-IIIA (HR 2.9), 34βE12+/K7+ (HR 1.90) and 34βE12-/K7+ (HR 3.7), were prognostic factors of poor cancer-specific survival (CSS) (p < 0.001). Validation in the Norwegian cohort confirmed that stage II-IIIA (HR 2.3), 34βE12+/K7+ (HR 1.6), and 34βE12-/K7+ (HR 2.0) were prognostic factors of poor CSS (p < 0.05). Multivariate Cox proportional-hazard analysis demonstrated that 34βE12+/K7 + and 34βE12+/K7 + status was significantly associated with poor overall survival (p < 0.05).
  
  
  CONCLUSIONS
  Keratin 34βE12/K7 expression is a prognostic parameter in resected early stage NSCLC that allows identification of high-risk NSCLC patients with poor cancer-specific and overall survival.
authors.affiliation: a Department of Oncology , Odense University Hospital , Odense , Denmark.|b Institute of Clinical Research, University of Southern Denmark , Odense , Denmark.|f Department of Oncology , Rigshospitalet , Copenhagen , Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Pøhl
authors.affiliation: b Institute of Clinical Research, University of Southern Denmark , Odense , Denmark.|c Department of Pathology , Odense University Hospital , Odense , Denmark.
authors.forename: Karen Ege
authors.initials: KE
authors.lastname: Olsen
authors.affiliation: d Department of Statistics , University of Southern Denmark , Odense , Denmark.
authors.forename: Rene
authors.initials: R
authors.lastname: Holst
authors.affiliation: g Institute of Clinical Medicine, University of Tromso , Tromso , Norway.|h Department of Oncology , University Hospital of North Norway , Tromso , Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.affiliation: i Institute of Medical Biology, University of Tromso , Tromso , Norway.|j Department of Clinical Pathology , University Hospital of North Norway , Tromso , Norway.
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.affiliation: g Institute of Clinical Medicine, University of Tromso , Tromso , Norway.|h Department of Oncology , University Hospital of North Norway , Tromso , Norway.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
authors.affiliation: i Institute of Medical Biology, University of Tromso , Tromso , Norway.|j Department of Clinical Pathology , University Hospital of North Norway , Tromso , Norway.
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.affiliation: g Institute of Clinical Medicine, University of Tromso , Tromso , Norway.|h Department of Oncology , University Hospital of North Norway , Tromso , Norway.
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
authors.affiliation: i Institute of Medical Biology, University of Tromso , Tromso , Norway.|j Department of Clinical Pathology , University Hospital of North Norway , Tromso , Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Richardsen
authors.affiliation: a Department of Oncology , Odense University Hospital , Odense , Denmark.|e Department of Cancer and Inflammation Research , Institute of Molecular Medicine, University of Southern Denmark , Odense , Denmark.
authors.forename: Henrik J
authors.initials: HJ
authors.lastname: Ditzel
authors.affiliation: a Department of Oncology , Odense University Hospital , Odense , Denmark.|b Institute of Clinical Research, University of Southern Denmark , Odense , Denmark.
authors.forename: Olfred
authors.initials: O
authors.lastname: Hansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053552:Keratin-7 / Q000378:metabolism*; D007633:Keratins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C121278:CK-34 beta E12; C507497:KRT7 protein, human; D053552:Keratin-7; D007633:Keratins