title: Clinical significance of TTF-1 protein expression and TTF-1 gene  amplification in lung adenocarcinoma.
abstract: The majority of lung adenocarcinomas express the lineage-specific thyroid transcription factor-1 (TTF-1). We recently reported that in a subset of lung adenocarcinomas the TTF-1 gene is amplified. Although the prognostic significance of TTF-1 expression has been previously investigated, the significance of TTF-1 amplification has not been established. We studied 89 consecutive patients with lung adenocarcinomas treated by surgery at Brigham and Women's Hospital between 1997 and 1999 and performed immunohistochemical analysis for TTF-1 expression and fluorescence in situ hybridization for TTF-1 amplification. We investigated associations between clinical-pathological characteristics, TTF-1 expression, TTF-1 amplification and overall survival. TTF-1 expression was categorized as high (48%), low (24%) or absent (28%). TTF-1 was amplified in 7% of cases. Patients with adenocarcinomas with low or high TTF-1 expression had a significantly better outcome than those with absent TTF-1 expression (median overall survival times of 72.4, 77.8 and 30.5 months, respectively, P = 0.002). In contrast, patients with adenocarcinomas with TTF-1 expression had a worse outcome if TTF-1 was amplified (median overall survival time 39.5 versus 87.5 months). In multivariate analysis, improved overall survival was independently predicted by TTF-1 expression in combination with no TTF-1 amplification (P < 0.001). In patients with lung adenocarcinoma, TTF-1 expression is a predictor of good outcome. Patients with no TTF-1 expression or TTF-1 expression and TTF-1 gene amplification tend to have a significantly worse prognosis than patients with TTF-1 expression and no TTF-1 gene amplification.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Justine A
authors.initials: JA
authors.lastname: Barletta
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.affiliation: Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Beow Y
authors.initials: BY
authors.lastname: Yeap
authors.affiliation: Medical Oncology.|Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Weir
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Johnson
authors.affiliation: Medical Oncology.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
authors.affiliation: Medical Oncology.|Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.affiliation: Department of Pathology, Memorial-Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.|Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Lucian R
authors.initials: LR
authors.lastname: Chirieac
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors