title: Thyroid transcription factor-1 expression prevalence and its clinical implications in non-small cell lung cancer: a high-throughput tissue microarray and immunohistochemistry study.
abstract: Thyroid transcription factor 1 (TTF-1), a homeodomain-containing transcription factor, plays a pivotal role in lung development, cell growth, and differentiation processes. The current literature reports considerable variation in frequency of TTF-1 protein expression in human non-small cell lung cancer (NSCLC). TTF-1 expression has not been extensively investigated as a prognostic marker in NSCLC. To assess the prevalence of TTF-1 expression, and to evaluate its potential role in disease prognosis, 140 stage I-IIIA NSCLCs with long-term follow-up were studied under uniform conditions using high-density tissue microarray (TMA) combined with immunohistochemistry. Patient survival and association of TTF-1 expression with clinicopathologic parameters were analyzed. One hundred twenty-six tumor samples were fully assessable after tissue processing. Sixty-four samples (50.8%) expressed TTF-1 and 62 (49.2%) displayed no expression. TTF-1 expression was significantly (P < 0.001) correlated with histological subtype: 51 adenocarcinomas (AdCs) (51 of 75; 68%) versus 9 squamous cell carcinomas (SCCs) (9 of 43; 21%) were TTF-1 positive. TTF-1 expression, performance status, nodal status, and tumor stage were significantly related to patient survival. In multivariate analysis, positive TTF-1 expression tended to favor a better patient outcome (P = 0.05). Overall, NSCLC patients with positive TTF-1 expression had a median survival of greater than 57.3 months, whereas those with negative expression had a median survival of 39.4 +/- 5.2 months (log-rank test, P = 0.0067). In this study we found that TTF-1 is predominately expressed in adenocarcinoma. The loss of TTF-1 expression was associated with aggressive behavior of NSCLCs. The results from this study strongly indicate that further investigation is warranted to better define the role of TTF-1 as a prognostic factor in this malignancy.
authors.affiliation: Lung Cancer Program, Roswell Park Cancer Institute, State University of New York, Buffalo, USA.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Tan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: George
authors.initials: G
authors.lastname: Deeb
authors.forename: Nithyia
authors.initials: N
authors.lastname: Ramnath
authors.forename: Harry K
authors.initials: HK
authors.lastname: Slocum
authors.forename: John
authors.initials: J
authors.lastname: Brooks
authors.forename: Richard
authors.initials: R
authors.lastname: Cheney
authors.forename: Sam
authors.initials: S
authors.lastname: Wiseman
authors.forename: Timothy
authors.initials: T
authors.lastname: Anderson
authors.forename: Gregory
authors.initials: G
authors.lastname: Loewen
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000401:mortality / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000556:secondary; D005260:Female; D016591:Histocytological Preparation Techniques; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008175:Lung Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D015996:Survival Rate; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors