Abstract

An association between epidermal growth factor receptor (EGFR) and clinical characteristics of non-small cell lung cancer (NSCLC) was reported ten years ago. In addition, a different type of relationship was seen in different ethic races. However, the relationship between these factors is not well understood in the Guangxi province. Up to now, there are only very limited data on the association of TTF1/EGFR protein positivity and EGFR mutation status in NSCLC. This study aims to investigate the role of EGFR gene mutation status on the clinical characteristics and the relationship with TTF-1/EGFR protein positivity of patients with NSCLC in Guangxi, China. 1506 samples from different patients with NSCLC were detected by amplification refractory mutation system for 29 hotspot mutations. Analysis of the relationship between clinical characteristics and EGFR mutation status was performed by using the crosstabs Chi-square and SPSS 21.0 software. Of 1506 samples, 537 (35.7%) revealed tyrosine kinase inhibitor (TKI) sensitive EGFR mutations with 27 (1.8%) cases harboring TKI resistant EGFR mutations or union co-existing EGFR-TKIs sensitive mutations. EGFR-TKIs sensitive mutations were not significantly associated with age and TNM-M stage (P = 0.863; P = 0.572, respectively). However, they were significantly associated with p-stage, TNM-T stage and TNM-N stage (P = 0.011, P < 0.001, P = 0.036, respectively). Immunohistochemical studies revealed that TTF-1 and EGFR protein expression level were all associated with EGFR mutation status (P < 0.001, P = 0.002, respectively). Of the 537 EGFR-TKIs sensitive mutation cases, the rates of exon 19-del, 18 G719X point, exon 21 L858R and L861Q points were 54.6, 0.9, 42.3 and 0.9%, respectively. EGFR TKI-sensitive mutations commonly occur in female, non-smoking and adenocarcinoma patients. The p-stage, TNM-T stage, TNM-N stage, EGFR and TTF-1 protein expression levels have close relationships with EGFR mutation status.

Highlights

  • According to the latest global cancer statistics, about 1.8 million new lung cancer cases occurred in 2012, accounting for nearly 13% of the total cancer diagnoses [1]

  • With regards to the epidermal growth factor receptor (EGFR) mutations in the different histological subtypes, this study showed that the highest EGFR-tyrosine kinase inhibitors (TKIs) sensitive mutation frequency occurred in adenocarcinoma (41.8% (493/1178)) and this was followed by adenosquamous carcinoma, (30.9% (21/68)), squamous cell carcinoma (6.6% (12/181)) and others (6.1% (11/79))

  • The p-stage has a close relationship with EGFR-TKIs sensitive mutations with the patients who in I stage have the most frequency EGFR-TKIs sensitive mutations

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Summary

Introduction

According to the latest global cancer statistics, about 1.8 million new lung cancer cases occurred in 2012, accounting for nearly 13% of the total cancer diagnoses [1]. Lung cancer was still the leading cause of cancer death among males and the leading cause of cancer among females in more developed countries. Non-small cell lung cancers (NSCLCs) account for approximately 85% of primary lung cancer cases [2, 3]. EGFR mutation was one of the most common mutations in NSCLC patients [11, 12]. The EGFR mutations showed a close relationship with clinical characteristics of patients with lung cancer and mainly appeared in non-smoking female patients with adenocarcinoma lung cancers [12,13,14]. The frequency of EGFR mutations have a wide variation worldwide, ranging from 31% to 66% in Asian patients [15,16,17] and 7.5% to 40% in Caucasians [18, 19]

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