Abstract

ObjectiveTo explore the relationship between TTF-1 and EGFR mutations in lung adenocarcinoma tissues to guide clinical treatment timely and effectively.Materials and Methodswe collected 664 tissue samples from patients with histologically confirmed lung adenocarcinoma from May 2010 to April 2013. All tumor tissues were collected prior to administering therapy. TTF-1 was detected byimmunohistochemistry and EGFR mutations by DNA direct sequencing. Finally, the correlation between TTF-1 expression and the presence of EGFR mutations was analyzed using χ2 test or Fisher’s exact test with SPSS software version 18.0.ResultsOf the 664 lung adenocarcinoma tissue samples, 18 were partially positive for TTF-1 (+−), and 636 were positive for TTF-1 (+) resulting in a total positive rate of 98.49% (+,+−)(including partial positive). In only 10 cases was the TTF-1 negative (−); the negative rate was 1.51%. There were 402 cases without an EGFR mutation and 262 cases with EGFR mutations; the rate of mutations was 39.46%. The location of the EGFR mutation was exon 19 for 121 cases resulting in a mutation rate in exon 19 of 18.22%. The location of the EGFR mutation was exon 21 for 141 cases resulting in a mutation rate in exon 21 of 21.23%. Exon 18 and 20 detected by DNA direct sequencing no mutations.A Fisher’s exact test was used to determine the correlation between EGFR mutations and TTF-1 expression.for the whole, TTF-1 positive expression(including partial positive) has correlation with EGFR mutations (p<0.001),especially for Exon 21 expression,the correlation is significant (p = 0.008).ConclusionIn lung adenocarcinomas, positive and partial positive TTF-1 expression has a significant positive correlation with EGFR mutations(exon 19 and 21). In clinical practice, TTF-1 expression combine with EGFR mutations, especially exon 21 mutation can guide clinical treatment timely for lung adenocarcinomas.

Highlights

  • Lung cancer is one of the leading causes of cancer death [1]the five-year survival rate of lung cancer patients is about 15% [2]

  • TTF-1 expression combine with epidermal growth factor receptor (EGFR) mutations, especially exon 21 mutation can guide clinical treatment timely for lung adenocarcinomas

  • With the discovery of epidermal growth factor receptor (EGFR) and the development of gefitinib and erlotinib, which can target therapy in EGFR mutations [3], the lifetime and quality of life of adenocarcinoma patients have greatly improved. It has been reported [4] that in the NEJ 002 clinical trial Patients whose NSCLC had EGFR mutations and were treated with gefitinib showed a median progression-free survival (PFS) of 10.8 months (HR 0.30, p,0.001) and a median overall survival of 30.5 months (HR, NR, p = 0.31). These results present the following question: can EGFR mutation status be used for lung adenocarcinoma patients as a marker for treatment decisions and as a prognostic indicator? The EGFR mutation status cannot be determined for some patients because of their tumor tissue cannot be acquired, the testing method and equipment used maybe different, and quality control limitations and so on [5]; timely effective treatment is not possible for those patients, and it is necessary to find efficient alternative indicators of EGFR mutation status

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Summary

Introduction

Lung cancer is one of the leading causes of cancer death [1]the five-year survival rate of lung cancer patients is about 15% [2]. With the discovery of epidermal growth factor receptor (EGFR) and the development of gefitinib and erlotinib, which can target therapy in EGFR mutations [3], the lifetime and quality of life of adenocarcinoma patients have greatly improved. It has been reported [4] that in the NEJ 002 clinical trial Patients whose NSCLC had EGFR mutations and were treated with gefitinib showed a median progression-free survival (PFS) of 10.8 months (HR 0.30, p,0.001) and a median overall survival of 30.5 months (HR, NR, p = 0.31). The purpose of this study was to clarify whether TTF-1 expression status can be used to predict EGFR mutation status to guide clinical treatment and improve the prognosis of patients with advanced lung cancer

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