Thyroid transcription factor-1 expression is significantly associated with mutations in exon 21 of the epidermal growth factor receptor gene in Chinese patients with lung adenocarcinoma

Abstract

Objective

The aim of this retrospective study was to investigate the relationship between thyroid transcription factor-1 (TTF-1) expression and epidermal growth factor receptor (EGFR) gene mutations in lung adenocarcinomas of Chinese patients.

Methods

There were 200 lung adenocarcinoma patients who were enrolled in this study. Tumor specimens of these patients were investigated for TTF-1 expression and mutations in EGFR using immunohistochemistry and a liquid chip platform for DNA analysis of slides with sections of formalin-fixed, paraffin-embedded specimens.

Results

The rates of TTF-1 expression and EGFR mutations were 81.5% and 45.5%, respectively, in the lung adenocarcinoma specimens of the recruited patients. Among female nonsmokers (n=72), 93.1% of specimens were positive for TTF-1 expression, and 63.9% had EGFR mutations. Of 89 patients with EGFR mutations, 83 (50.9%) specimens were simultaneously positive for TTF-1 expression. Kaplan–Meier analysis of all patient specimens found that postoperative survival time was not significantly associated with TTF-1 expression and the presence of EGFR mutations. However, patients with disease stages III–IV whose tumors were positive for TTF-1 expression and EGFR mutations had better postoperative survival than similar patients whose tumors were negative for TTF-1 expression and EGFR mutations.

Conclusion

Our study showed a significant association between TTF-1 positivity and the presence of EGFR mutations (exon 21) in the Chinese lung adenocarcinoma patients. We further identify that patients with disease stages III–IV who were positive for TTF-1 expression and EGFR mutations had a better postoperative survival than those patients who were negative for TTF-1 expression and EGFR mutations. Therefore, TTF-1 might be a potential prognostic biomarker for stages III–IV lung adenocarcinoma patients. In clinical practice, TTF-1 expression may be a marker for planning therapy for certain patients with lung adenocarcinoma, especially for selection of EGFR tyrosine kinase inhibitors.

Keywords:

• EGFR
• lung adenocarcinoma
• survival
• TTF-1

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81172233, 81372306, and 81301812), the Specialized Research Fund for the Doctoral Program of Higher Education (20131202120004), the Tianjin key project of Natural Science Foundation (12JCZDJC24400), the Tianjin Natural Science Foundation (13JCYBJC22600), the Tianjin Science and Technology Support Program (12ZCDZSY16100), and the Tianjin Educational Committee Foundation (20120117). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosure

The authors report no conflicts of interest in this work.