Thyroid transcription factor-1 expression is an independent predictor of recurrence and correlates with the IASLC/ATS/ERS histologic classification in patients with stage I lung adenocarcinoma

Authors

  • Kyuichi Kadota MD, PhD,

    1. Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan
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  • Jun-ichi Nitadori MD, PhD,

    1. Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Inderpal S. Sarkaria MD,

    1. Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Camelia S. Sima MD, MS,

    1. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Xiaoyu Jia MS,

    1. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Akihiko Yoshizawa MD, PhD,

    1. Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan
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  • Valerie W. Rusch MD, FACS,

    1. Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • William D. Travis MD,

    1. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Prasad S. Adusumilli MD, FACS

    Corresponding author
    1. Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, New York
    • Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
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    • Fax: (646) 422-2340


Abstract

BACKGROUND:

In the current study, the authors investigated whether thyroid transcription factor-1 (TTF-1) expression is correlated with the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and whether it stratifies patients with stage I lung adenocarcinoma with respect to disease recurrence.

METHODS:

Patients with stage I lung adenocarcinoma were classified according to the IASLC/ATS/ERS classification. Tissue microarrays were constructed and immunostaining for TTF-1 was performed. A total of 452 cases were available for analysis. Tumors were dichotomized based on the intensity of nuclear TTF-1 expression as negative (score of 0) or positive (score of 1–3). The cumulative incidence of recurrence (CIR) was used to estimate disease recurrence probabilities.

RESULTS:

TTF-1 expression was identified in 92% of patients, including 100% of patients with minimally invasive or lepidic-predominant adenocarcinoma, 94% of patients with acinar-predominant adenocarcinoma, 98% of patients with papillary-predominant adenocarcinoma, 93% of patients with micropapillary-predominant adenocarcinoma, 86% of patients with solid-predominant adenocarcinoma, 67% of patients with colloid-predominant adenocarcinoma, and 47% of patients with invasive mucinous carcinoma. The CIR for patients with negative TTF-1 expression (n = 34 patients; 5-year CIR, 40%) was significantly higher than that for patients with positive TTF-1 expression (n = 418 patients; 5-year CIR, 15%) (P < .001). Among the patients with intermediate-grade tumors, the CIR for patients with negative TTF-1 expression (n = 16 patients; 5-year CIR, 45%) was significantly higher than that for patients with positive TTF-1 expression (n = 313 patients; 5-year CIR, 14%) (P < .001). On multivariate analysis, negative TTF-1 expression was found to be significantly correlated with an increased risk of disease recurrence (hazards ratio, 2.55; P = .009).

CONCLUSIONS:

TTF-1 expression was found to be an independent predictor of disease recurrence, stratifying intermediate-grade tumors into 2 prognostic subsets, and it correlates with the IASLC/ATS/ERS classification. Cancer 2013. © 2012 American Cancer Society.

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