Irish Journal of Medical Science (1971 -)

, Volume 188, Issue 1, pp 69–74 | Cite as

Absence of thyroid transcription factor-1 expression is associated with poor survival in patients with advanced pulmonary adenocarcinoma treated with pemetrexed-based chemotherapy

  • Mark K. Doherty
  • Emer O’Connor
  • David Hannon
  • Aine O’Reilly
  • Daphne Yen
  • Maeve Redmond
  • Liam M. Grogan
  • Bryan T. Hennessy
  • Oscar S. Breathnach
  • Patrick G. MorrisEmail author
Original Article



Adenocarcinoma is the commonest histologic subtype of lung cancer and is often identified by immunohistochemical staining for thyroid transcription factor-1 (TTF-1). However, up to 20% of lung adenocarcinomas do not express TTF-1, and there is uncertainty regarding the significance of this. We aimed to evaluate the prognostic effect of TTF-1 expression status on survival in patients treated with pemetrexed-based chemotherapy for advanced adenocarcinoma of the lung.


This retrospective study included patients treated with pemetrexed-based chemotherapy for stage IIIB/IV lung adenocarcinoma, who had known TTF-1 expression status. Clinical and demographic data were obtained from medical records. Overall survival (OS) was estimated using the Kaplan-Meier method, and differences in survival between groups assessed using the Cox proportional hazards model.


Forty-four patients were identified with documented TTF-1 expression: 35 with TTF-1-positive and 9 with TTF-1-negative disease. Patients in the TTF-1-negative group had poorer performance scores than those in the TTF-1-positive group (ECOG 2: 67 vs 20%, p = 0.008), and received less chemotherapy (median cycles 2 vs 4, p = 0.009), and were fewer in treatment with doublet regimens (22 vs 69%, p = 0.013). OS was significantly shorter in the TTF-1-negative group than in the TTF-1-positive group (2.4 vs 11.5 months, HR 8.38, p < 0.0001).


In this group of patients treated with pemetrexed-based chemotherapy for advanced pulmonary adenocarcinoma, absence of TTF-1 expression was associated with an aggressive tumor phenotype, poorer performance status, and poor survival. This subgroup of patients should be recognized as having a distinct clinical course, with limited benefit from standard chemotherapy.


Biomarker Chemotherapy Non-small cell lung cancer Pemetrexed Thyroid transcription factor-1 TTF-1 


Funding source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Pemetrexed is manufactured by Eli Lilly, Indianapolis, IN, USA. This company had no role in this work.

Compliance with ethical standards

This study involved human participants and was performed in accordance with the ethical standards of the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Royal Academy of Medicine in Ireland 2018

Authors and Affiliations

  • Mark K. Doherty
    • 1
  • Emer O’Connor
    • 1
  • David Hannon
    • 1
  • Aine O’Reilly
    • 1
  • Daphne Yen
    • 1
  • Maeve Redmond
    • 2
  • Liam M. Grogan
    • 1
    • 4
  • Bryan T. Hennessy
    • 1
    • 3
    • 4
  • Oscar S. Breathnach
    • 1
    • 4
  • Patrick G. Morris
    • 1
    • 3
    • 4
    Email author
  1. 1.Cancer Clinical Trials and Research UnitBeaumont HospitalDublinIreland
  2. 2.Department of PathologyBeaumont HospitalDublinIreland
  3. 3.Royal College of Surgeons of IrelandDublinIreland
  4. 4.Department of Medical OncologyBeaumont HospitalDublinIreland

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