Clinical significance of TTF-1 protein expression and TTF-1 gene amplification in lung adenocarcinoma - PubMed (original) (raw)

. 2009 Aug;13(8B):1977-1986.

doi: 10.1111/j.1582-4934.2008.00594.x.

Sven Perner 1, A John Iafrate 2, Beow Y Yeap 3, Barbara A Weir 4 5, Laura A Johnson 1, Bruce E Johnson 4, Matthew Meyerson 4 5, Mark A Rubin 1, William D Travis 6, Massimo Loda 1 5, Lucian R Chirieac 1

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Clinical significance of TTF-1 protein expression and TTF-1 gene amplification in lung adenocarcinoma

Justine A Barletta et al. J Cell Mol Med. 2009 Aug.

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.

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Figures

Figure 1

Figure 1

TTF1 amplification by fluorescence in situ hybridization (FISH). (A) FISH for NKX2–1 (TTF1, red) and a chromosome 14 reference probe (green) on a lung adenocarcinoma specimen with high‐level amplification of the NKX2–1 probe. Nuclei are stained with DAPI (blue). The box shows a single nucleus. (B) FISH on lung adenocarcinoma tissue without amplification. The boxed area shows a representative nucleus. (C) FISH for NKX2–1 (red) and a chromosome 14 reference probe (green) on a lung adenocarcinoma specimen with polysomy. Nuclei are stained with DAPI (blue). The box shows a single nucleus.

Figure 2

Figure 2

Diagram of representative tissue cores of the TMA illustrating the semi‐quantitative assessment of TTF‐1 expression in lung adenocarcinoma. TTF‐1 expression was semi‐quantitatively assigned to one of three categories: (A) No expression (absent staining = 0). (B) Low expression (weak staining intensity = 1), (C) High expression (strong staining intensity = 2).

Figure 3

Figure 3

Kaplan–Meier estimates of overall survival among patients with lung adenocarcinoma according to TTF‐1 expression and TTF‐1 amplification. (A) The overall survival time was significantly longer for patients with adenocarcinomas with high or low TTF‐1 expression, than for patients with adenocarcinomas with absent TTF‐1 expression (_P_= 0.002). (B) There was no difference in overall survival between patients with adenocarcinomas with or without TTF‐1 gene amplification (_P_= 0.508). (C) There was a trend toward a worse overall survival for patients with adenocarcinomas with TTF‐1 expression and TTF‐1 gene amplification compared to patients with adenocarcinomas with TTF‐1 expression and without TTF‐1 amplification (median 39.5 versus 87.5 months, _P_= 0.113).

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