12P - Thyroid transcription factor-1 as a prognosticator in patients with metastatic lung adenocarcinoma without EGFR sensitizing mutations

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Lung and other Thoracic Tumours
Pathology/Molecular Biology
Presenter Ji Young Park
Citation Annals of Oncology (2017) 28 (suppl_2): ii1-ii5. 10.1093/annonc/mdx090
Authors J.Y. Park1, S.H. Jang1, J. Kim1, S. Park1, Y.I. Hwang1, K. Jung1, J.W. Seo2
  • 1Division Of Pulmonary, Allergy And Critical Care Medicine, Hallym University Sacred Heart Hospital, 14068 - Anyang/KR
  • 2Pathology, Hallym University Sacred Heart Hospital, 14068 - Anyang/KR



Thyroid transcription factor-1 (TTF-1) expression is known not only as a diagnostic marker but also a good prognosticator among patients with lung adenocarcinoma. However, good prognosis of TTF-1 expression might be due to epidermal growth factor receptor (EGFR) sensitizing mutations because of the positive correlation between TTF-1 expression and EGFR mutations. The purpose of this study was to explore prognostic impact of TTF-1 expression according to EGFR sensitizing mutation status in lung adenocarcinoma.


This is a retrospective analysis of patients with 1) stage IV lung adenocarcinoma having available TTF-1 immunohistochemistry result, 2) ECOG performance status 0-2, and 3) receiving systemic anti-cancer treatment. The data were extracted from the registry of Hallym University Sacred Heart Hospital in Korea, between March 2006 and March 2016.


Of the 697 patients with lung adenocarcinoma, 144 patients were included for analysis. The mean age was 65.2 ± 11.6 years (female; 42.4%). EGFR sensitizing mutations were detected in 72/144 (50.0%) patients. TTF-1 was positive in 116/144 (80.6%) patients, and it had a significant correlation with EGFR sensitizing mutations (p < 0.001). Patients with TTF-1 positive lung adenocarcinoma had longer overall survival (OS) than TTF-1 negative (21.4 vs. 6.5 months, p < 0.001). In Cox regression analysis, TTF-1 positivity (hazard ratio [HR] 0.50; 95% CI: 0.31-0.83; p = 0.007), Stage IV, M1a (HR 0.62; 95% CI, 0.40–0.97; p = 0.034), good performance status (ECOG=0; HR 0.52; 95% CI, 0.33–0.82; p = 0.005) and EGFR sensitizing mutations (HR 0.62; 95% CI, 0.39–0.97; p = 0.038) were independently associated with prolonged OS. In the subgroup of patients with wild type EGFR adenocarcinoma, TTF-1 positivity was also good prognosticator for OS (HR 0.58; 95% CI: 0.33-0.99; p = 0.046), and for progression-free survival (PFS) of the first-line cytotoxic chemotherapy (HR 0.43; 95% CI, 0.24–0.78; p = 0.006). (Table).rnTable: 12P

Cox proportional hazard model of overall survival for 72 patients with lung adenocarcinoma harboring wild type EGFR

CovariateUnivariate analysisMultivariate analysis
P valueHR (95% CI)P valueHR (95% CI)
Age < 70 vs. ≥ 700.9860.995 (0.607-1.633)0.5631.175 (0.680-2.030)
Female vs. male0.0060.425 (0.231-0.780)0.4700.563 (0.119-2.676)
Never smoker vs. ever smoker<0.0010.443 (0.248-0.790)0.9800.981 (0.222-4.330)
Stage IV, M1a vs. M1b0.0620.602 (0.353-1.027)0.0460.569 (0.327-0.991)
ECOG 0 vs. 1-20.0160.529 (0.316-0.887)0.0760.587 (0.325-1.057)
TTF-1 positive vs. negative0.0600.607 (0.360-1.022)0.0460.575 (0.334-0.991)
Pemetrexed, 1st line vs. non-pemetrexed containing regimen0.8620.956 (0.576-1.587)0.4800.829 (0.492-1.395)

HR=Hazard ratio; CI=confidence intervals, ECOG = Eastern Cooperative Oncology Group; EGFR = epidermal growth factor receptor; TTF-1 = thyroid transcription factor 1.



TTF-1 expression was a good prognosticator for OS and PFS in patients with stage IV lung adenocarcinoma without EGFR sensitizing mutations.

Clinical trial identification

Legal entity responsible for the study

Hallym University Sacred Heart Hospital Institutional Ethics Committee




All authors have declared no conflicts of interest.