OncoTargets and Therapy (Aug 2016)
EGFR protein expression using a specific intracellular domain antibody and PTEN and clinical outcomes in squamous cell lung cancer patients with EGFR-tyrosine kinase inhibitor therapy
Abstract
Hyun Chang,1,2,* Jisu Oh,1,3,* Xianglan Zhang,4 Yu Jung Kim,1 Jae Ho Lee,1 Choon-Taek Lee,1 Jin-haeng Chung,5 Jong-Seok Lee1 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, 2Division of Medical Oncology, Department of Internal Medicine, International St Mary’s Hospital, College of Medicine, Catholic Kwandong University, Incheon, 3Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 4Department of Pathology, Yanbian University Hospital, Yanji, People’s Republic of China; 5Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea *These authors contributed equally to this work Purpose: The aim of this research was to examine the molecular and clinical features that are related with EGFR-tyrosine kinase inhibitor (EGFR-TKI) efficacy in previously treated patients with squamous cell carcinoma of the lung (SCCL). Materials and methods: This retrospective study included 67 SCCL patients with obtainable lung cancer tissue and records on EGFR-TKI treatment response and survival. EGFR protein expression in lung cancer tissue was measured by immunohistochemistry with a specific antibody that recognizes the intracellular domain (ID) of EGFR. PTEN expression in lung cancer tissue was also evaluated with immunohistochemistry. PI3KCA gene amplification was detected by quantitative real-time polymerase chain reaction, and FGFR1 amplification was assessed by fluorescent in situ hybridization. Results: EGFR ID expression (hazard ratio [HR] 0.53, P=0.022) and Eastern Cooperative Oncology Group (ECOG) performance status (PS) (HR 0.43, P=0.022) were significantly related with progression-free survival following EGFR-TKIs treatment. PTEN expression (HR 0.52, P=0.025) was significantly related to overall survival. The group of EGFR-positive or PTEN-positive patients with ECOG PS of 0 or 1 had better clinical outcomes than patients who were EGFR-negative and PTEN-negative or who had poor ECOG PS with longer median progression-free survival (2.1 vs 1.0 months, P=0.05) and overall survival (6.2 vs 2.1 months, P=0.05). Conclusion: EGFR expression using an ID-specific antibody and PTEN protein expression may be used to identify SCCL patients who might benefit from EGFR-TKI treatment. Keywords: EGFR, tyrosine kinase inhibitor, squamous cell carcinoma, lung, intracellular domain, PTEN
