Thyroid transcription factor-1 expression prevalence and its clinical implications in non-small cell lung cancer: A high-throughput tissue microarray and immunohistochemistry study

Dongfeng Tan, Qiang Li, George Deeb, Nithyia Ramnath, Harry K. Slocum, John Brooks, Richard Cheney, Sam Wiseman, Timothy Anderson, Gregory Loewen

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)597-604
Number of pages8
JournalHuman Pathology
Volume34
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

Keywords

  • Immunohistochemistry
  • Non-small cell lung cancer
  • Thyroid transcription factor-1
  • Tissue microarray

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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