EGFR with TKI-sensitive mutations in exon 19 is highly expressed and frequently detected in Chinese patients with lung squamous carcinoma

Abstract

Aadil Ahmed Memon,1 Haiping Zhang,2 Ye Gu,3 Qian Luo,4 Jiajun Shi,1 Zixin Deng,1 Jian Ma,5 Wei Ma1 1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 2Oncology Department, 3Endoscope Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 4Core Facility and Technical Service Center, School of Life Science and Biotechnology, Shanghai Jiao Tong University, 5Pneumology Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Abstract: Recently, tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment for advanced non-small cell lung cancer (NSCLC), significantly improving the treatment outcomes of lung adenocarcinoma patients with the EGFR mutation. However, the application of TKIs for lung squamous cell carcinoma (SCC), the second largest pathological subtype of NSCLC, remains controversial because available data for the EGFR mutation profile and frequency in SCC patients are limited. In this study, 89 bronchoscopic–biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation, using improved polymerase chain reaction-denature gel gradient electrophoresis. EGFR exon 19 mutations were detected in 77 of 89 (86.5%) patients, and included six kinds of point mutations (11.6%) and two deletions (Del_747-751 [64.9%] and Del_746-751 [23.3%]). We found that the proportion of mutated EGFR varied from 0.98% to 100% in positive specimens and increased with the development of the disease. The difference of proportion between Stage IV patients and Stage II patients or Stage III patients was significant (P<0.001). These results provided valuable clues to explain the reason why patients harboring the same mutation responded distinctly to TKI treatment. Del_747-751 and Del_746-751 were the dominant mutations in the assayed SCC patients (76.4%), and both belong to the EGFR–TKI-sensitive mutation. Recently research demonstrated that Del_746-751 patients have better response to EGFR-TKI than Del_L747-751 patients. However, our study indicated that majority of SCC patients (55.5%) carried Del_ L747-751. We suggest that the unique clinic features of SCC should be further studied to reveal the mechanism of poorer treatment outcome of EGFR–TKI therapy, and that a better treatment plan and more specific, potent targeted drugs for lung SCC need to be developed. Keywords: lung squamous carcinoma, EGFR exon 19, mutation profile, PCR-DGGE, tyrosine kinase inhibitors

Keywords

• Lung Squamous Carcinoma
• EGFR exon 19
• Mutation Profile
• PCR-DGGE
• Tyrosine Kinase Inhibitors.