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J Thorac Dis. 2019 May;11(5):1919-1928. doi: 10.21037/jtd.2019.04.102.

Correlation between thyroid transcription factor-1 expression, immune-related thyroid dysfunction, and efficacy of anti-programmed cell death protein-1 treatment in non-small cell lung cancer.

Author information

1
Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
2
Division of Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

Abstract

Background:

Recent studies have suggested a correlation between immune-related thyroid dysfunction (irTD) and the superior efficacy of anti-programmed cell death protein-1 (anti-PD-1) treatment in non-small cell lung cancer (NSCLC). Embryologically, the lung and thyroid are similar in origin, and thyroid transcription factor-1 (TTF-1) expresses in both organs, including NSCLC. We explored our hypothesis that TTF-1 expression in NSCLC might correlate with irTD incidence and anti-PD-1 treatment efficacy.

Methods:

We identified 132 patients with NSCLC treated with anti-PD-1 antibody at our hospital between December 2015 and June 2017. We evaluated TTF-1 expression in tumor by immunohistochemistry using a mouse monoclonal antibody (clone 8G7G3/1, 1:100, Dako). IrTD was defined as two or more successive abnormal levels of thyroid-stimulating hormone (TSH) during anti-PD-1 treatment. We retrospectively assessed correlations between TTF-1 expression in tumor, irTD incidence, and anti-PD-1 treatment efficacy.

Results:

Of 132 patients, 67 (51%) and 65 (49%) were positive and negative for TTF-1, respectively. We observed irTD in 19 patients (6 positives and 13 negatives for TTF-1). The incidence of irTD was 9% and 20% in TTF-1-positive and TTF-1-negative NSCLCs, respectively (P=0.086). Particularly, in non-squamous (NSQ) cell carcinomas, the irTD incidence was significantly higher in patients negative for TTF-1 (30%) than in those positive for TTF-1 (9%; P=0.010), and TTF-1 expression was identified as a significant risk factor for irTD on multivariate logistic regression analysis [odds ratio (OR), 0.18; 95% confidence interval (CI), 0.05-0.59; P=0.005]. Furthermore, longer median progression-free survival (10.3 months) was observed in patients with TTF-1-negative NSCLC with irTD compared to those with TTF-1-positive NSCLC with irTD, TTF-1-positive NSCLC without irTD, and TTF-1-negative NSCLC without irTD (4.2, 1.4, and 2.4 months, respectively).

Conclusions:

TTF-1 expression in NSCLC might correlate with irTD and anti-PD-1 treatment efficacy.

KEYWORDS:

Non-small cell lung cancer (NSCLC); nivolumab; pembrolizumab; programmed cell death protein-1 (PD-1); thyroid transcription factor-1 (TTF-1)

Conflict of interest statement

Conflict of Interest: M Nishio received research funding from Novartis, ONO Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, TAIHO Pharmaceutical, Eli Lilly, Pfizer, Astellas Pharma and AstraZeneca, and honoraria from Pfizer, Bristol-Myers Squibb, ONO Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, TAIHO Pharmaceutical and AstraZeneca. A Horiike received research funding from Chugai Pharmaceutical, Quintiles, MSD oncology, and Abbvie, and honoraria from Chugai Pharmaceutical, Eli Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, ONO Pharmaceutical. Y Ishikawa received research funding from Daiichi Sankyo, and honoraria from Bristol-Myers Squibb, MSD Oncology, ONO Pharmaceutical, Novartis. N Yanagitani received honoraria from MSD Oncology, Bristol-Myers Squibb, ONO Pharmaceutical. The other authors have no conflicts of interest to declare.

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