Correlation between Expression of Thyroid Transcription Factor 1 and Gene Mutation of Epidermal Growth Factor Receptor in Patients with Resectable Lung Adenocarcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LINHai-ping ¹ ,  CAOZi-ang ¹ , YANGYi ² , YEQing ¹

1. Department of Thoracic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, P. R. China;
2. Department of Cardiothoracic Surgery, Shanghai No.6 Hospital, Shanghai 200233, P. R. China;

Corresponding author：

CAOZi-ang, Email: dr_cao@163.com

Keywords：

Lung cancer; Adenocarcinoma; Thyroid transcription factor 1; Epidermal growth factor receptor; Gene mutation

DOI：

10.7507/1007-4848.20140146

Video：

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Objective To explore the correlation between expression of thyroid transcription factor-1 (TTF-1) and gene mutation of epidermal growth factor receptor (EGFR) in patients with resectable lung adenocarcinoma (LAC). Method Sixty-seven LAC patients who underwent surgical resection in the Department of Cardiothoracic Surgery of Shanghai No.6 Hospital and Department of Thoracic Surgery, Renji Hospital, School of Medicine of Shanghai Jiaotong University from June 2009 to December 2012 were enrolled in this study. There were 40 male and 27 female patients with their age of 37-79 (56.7±1.8) years. TTF-1 expression was detected by immunohistochemistry. EGFR gene mutation was examined with mutant-enriched polymerase chain reaction. The correlation between TTF-1 expression and EGFR gene mutation was analyzed with corrected chi-square test. Results Among the 67 LAC samples, 57 samples were TTF-1 positive and 10 samples were TTF-1 negative. There was EGFR gene mutation in 44 samples. EGFR gene mutation rate was 73.7% (42/57) in TTF-1 positive patients and 20.0% (2/10) in TTF-1 negative patients. The sensitivity of TTF-1 expression to predict EGFR mutation was 95.5%, and the specificity was 34.8%. Conclusion EGFR gene mutation rate is higher in LAC patients with positive TTF-1 expression. Positive TTF-1 expression can be used to predict EGFR gene mutation in LAC patients.

Citation： LINHai-ping, CAOZi-ang, YANGYi, YEQing. Correlation between Expression of Thyroid Transcription Factor 1 and Gene Mutation of Epidermal Growth Factor Receptor in Patients with Resectable Lung Adenocarcinoma. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2014, 21(4): 518-521. doi: 10.7507/1007-4848.20140146 Copy

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2.	Asano H, Toyooka S, Tokumo M, et al. Detection of EGFR gene mutation in lung cancer by mutant-enriched polymerase chain reaction assay. Clin Cancer Res, 2006, 12 (1):43-48.
3.	Jiang B, Liu F, Yang L, et al. Serum detection of epidermal growth factor receptor gene mutations using metant-enriched sequencing in Chinese patients with advanced non-small cell lung cancer. J Int Med Res, 2011, 39 (4):1392-1401.
4.	Inoue A, Kobayashi K, Maemondo M, et al. Updated overall survival results from a randomized phaseⅢtrial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol, 2013, 24 (1):54-59.
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7.	Berghmans T, Paesmans M, Mascaux C, et al. Thyroid transcription factor 1-a new prognostic factor in lung cancer:a meta-analysis. Ann Oncol, 2006, 17 (11):1673-1676.
8.	Tang X, Kadara H, Behrens C, et al. Abnormalities of the TITF-1 lineage-specific oncogene in NSCLC:implications in lung cancer pathogenesis and prognosis. Clin Cancer Res, 2011, 17 (8):2434-2443.
9.	Vallee A, Sagan C, Le Loupp A, et al. Detection of EGFR gene mutations in non-small cell lung cancer:Lessons from a single-institution routine analysis of 1, 403 tumor samples. Int J Oncol, 2013, 43 (4):1045-1051.
10.	Somaiah N, Garrett-Mayer E, Huang X, et al. Use of negative thy-roid transcription factor (TTF-1) status to predict for negative epid-ermal growth factor receptor (EGFR) mutations (Mts) status with a high negative predictive value (NPV) in patients (pts) with adenocarcinomas (AC) of the lung. J Clin Oncol, 2011, 29 (Suppl):7530.
11.	Sun P L, Seol H, Lee H J, et al. High incidence of EGFR mutations in Korean men smokers with no intratumoral heterogeneity of lung adenocarcinomas:correlation with histologic subtypes, EGFR/TTF-1 expressions and clinical features. J Thorac Oncol, 2012, 7 (2):323-330.
12.	Vincenten J, Smit EF, Vos W, et al. Negative NKX2-1 (TTF-1) as temporary surrogate marker for treatment selection during EGFR-mutation analysis in patients with non-small-cell lung cancer. J Thorac Oncol, 2012, 7 (10):1522-1527.
13.	Chung KP, Huang YT, Chang YL. Clinical significance of thyroid transcription factor-1 in advanced lung adenocarcinoma under epid-ermal growth factor receptor tyrosine kinase inhibitor treatment. Chest, 2012, 141 (2):420-428.
14.	刘瑞青, 申淑景, 马杰, 等.肺腺癌组织中TTF-1和SPA的表达对EGFR突变的临床预测价值.第三军医大学学报, 2012, 34 (22):2314-2317.
15.	Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/American thoracic society European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thoracic Oncol, 2011, 6 (2):244-285.
16.	刘标, 时姗姗, 王璇, 等. 2011年肺腺癌新分类在评估组织学类型与分子学改变相关性中的意义.中华病理学杂志, 2012, 42 (8), 505-510.
17.	Thunnissen E, Boers E, Heideman DA, et al. Correlation of immun-ohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma. Virchows Arch, 2012, 461 (6):629-638.
18.	Schnabel PA, Smit E, Carpeño J, et al. Influence of histology and biomarkers on first-line treatment of advanced non-small cell lung cancer in routine care setting:baseline results of an observational study (FRAME). Lung Cancer, 2012, 78 (3):263-269.
19.	Hartel PH, Hartel JV, Fanburg-Smith JC. Toward personalized medicine of lung cancer:response to nontargeted therapy in invasive pulmonary adenocarcinoma as a function of tumor cell differentiation. Int J Surg Pathol, 2013, 21 (3):224-228.
20.	Behrens C, Solis Soto LM, et al. EZH2 protein expression associates with the early pathogenesis, tumor progression and prognosis of non-small cell lung carcinoma. Clin Cancer Res, 2013, 19 (23):6556-6565.

1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin, 2010, 60 (5):277-300.
2. Asano H, Toyooka S, Tokumo M, et al. Detection of EGFR gene mutation in lung cancer by mutant-enriched polymerase chain reaction assay. Clin Cancer Res, 2006, 12 (1):43-48.
3. Jiang B, Liu F, Yang L, et al. Serum detection of epidermal growth factor receptor gene mutations using metant-enriched sequencing in Chinese patients with advanced non-small cell lung cancer. J Int Med Res, 2011, 39 (4):1392-1401.
4. Inoue A, Kobayashi K, Maemondo M, et al. Updated overall survival results from a randomized phaseⅢtrial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol, 2013, 24 (1):54-59.
5. Fukuoka M, Wu Y, Thongprasert S, et al. Biomarker analyses from a phase Ⅲ, randomized, open-label, first-line study of gefitinib (G) versus carboplatin/paclitaxel (C/P) in clinically selected patients (pts) with advanced non-small cell lung cancer (NSCLC) in Asia (IPASS).J Clin Oncol, 2011, 29 (21):2866-2874.
6. 张岩巍, 韩宝惠.非小细胞肺癌EGFR突变检测的研究和应用进展.临床肿瘤学杂志, 2012, 17 (8):760-764.
7. Berghmans T, Paesmans M, Mascaux C, et al. Thyroid transcription factor 1-a new prognostic factor in lung cancer:a meta-analysis. Ann Oncol, 2006, 17 (11):1673-1676.
8. Tang X, Kadara H, Behrens C, et al. Abnormalities of the TITF-1 lineage-specific oncogene in NSCLC:implications in lung cancer pathogenesis and prognosis. Clin Cancer Res, 2011, 17 (8):2434-2443.
9. Vallee A, Sagan C, Le Loupp A, et al. Detection of EGFR gene mutations in non-small cell lung cancer:Lessons from a single-institution routine analysis of 1, 403 tumor samples. Int J Oncol, 2013, 43 (4):1045-1051.
10. Somaiah N, Garrett-Mayer E, Huang X, et al. Use of negative thy-roid transcription factor (TTF-1) status to predict for negative epid-ermal growth factor receptor (EGFR) mutations (Mts) status with a high negative predictive value (NPV) in patients (pts) with adenocarcinomas (AC) of the lung. J Clin Oncol, 2011, 29 (Suppl):7530.
11. Sun P L, Seol H, Lee H J, et al. High incidence of EGFR mutations in Korean men smokers with no intratumoral heterogeneity of lung adenocarcinomas:correlation with histologic subtypes, EGFR/TTF-1 expressions and clinical features. J Thorac Oncol, 2012, 7 (2):323-330.
12. Vincenten J, Smit EF, Vos W, et al. Negative NKX2-1 (TTF-1) as temporary surrogate marker for treatment selection during EGFR-mutation analysis in patients with non-small-cell lung cancer. J Thorac Oncol, 2012, 7 (10):1522-1527.
13. Chung KP, Huang YT, Chang YL. Clinical significance of thyroid transcription factor-1 in advanced lung adenocarcinoma under epid-ermal growth factor receptor tyrosine kinase inhibitor treatment. Chest, 2012, 141 (2):420-428.
14. 刘瑞青, 申淑景, 马杰, 等.肺腺癌组织中TTF-1和SPA的表达对EGFR突变的临床预测价值.第三军医大学学报, 2012, 34 (22):2314-2317.
15. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/American thoracic society European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thoracic Oncol, 2011, 6 (2):244-285.
16. 刘标, 时姗姗, 王璇, 等. 2011年肺腺癌新分类在评估组织学类型与分子学改变相关性中的意义.中华病理学杂志, 2012, 42 (8), 505-510.
17. Thunnissen E, Boers E, Heideman DA, et al. Correlation of immun-ohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma. Virchows Arch, 2012, 461 (6):629-638.
18. Schnabel PA, Smit E, Carpeño J, et al. Influence of histology and biomarkers on first-line treatment of advanced non-small cell lung cancer in routine care setting:baseline results of an observational study (FRAME). Lung Cancer, 2012, 78 (3):263-269.
19. Hartel PH, Hartel JV, Fanburg-Smith JC. Toward personalized medicine of lung cancer:response to nontargeted therapy in invasive pulmonary adenocarcinoma as a function of tumor cell differentiation. Int J Surg Pathol, 2013, 21 (3):224-228.
20. Behrens C, Solis Soto LM, et al. EZH2 protein expression associates with the early pathogenesis, tumor progression and prognosis of non-small cell lung carcinoma. Clin Cancer Res, 2013, 19 (23):6556-6565.

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Correlation between Expression of Thyroid Transcription Factor 1 and Gene Mutation of Epidermal Growth Factor Receptor in Patients with Resectable Lung Adenocarcinoma

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