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P2.03b-078 MET Gene Amplification and Overexpression in Chinese NSCLC Patients without EGFR Mutations
January 2017
related biopsies. Tumor sufficiency was confirmed prior to implantation into non-obese severe combined immunodeficient (NOD-SCID) mice, with successful engraftment defined as propagation beyond first passage; unsuccessful implantations had no palpable tumor after 6 months. Results: 72/82 (88%) approached patients consented; 49/72 (68%) had adequate tumor tissue for implantation (71% stage III/IV): 46 adenocarcinomas, 2 squamous cell carcinoma, 1 LCNEC. 36/49 (73%) were lifetime never smokers. Patients received adjuvant chemotherapy (3), TKI therapy (15), both (5), or no treatment (26) prior to sampling. Tumor samples were taken from surgically resected lung (18), metastatic adrenal (1) and brain (2), CT-guided lung biopsies (5), endoscopic ultrasoundguided (EBUS) biopsies (6), and thoracentesis pleural fluid (17) specimens. Twenty-eight implanted tumors were EGFR+ (12 exon19 deletions, 2 exon19 deletion/ T790M, 1 exon19 del/exon18 mutation, 12 L858R, and 1 L858R/T790M); 7 had ALK-rearrangements, and 1 had ROS1-rearrangement. Engraftment rates of 31 assessable implanted tumors were as follows: lung resections 12/12 (100%), metastatic resections 2/3 (67%), CT- or EBUSguided biopsies 1/5 (20%), and pleural fluid 2/11 (18%); Engraftment rate was associated with no prior treatment (14/17 no treatment vs 3/14 any treatment, p¼0.001). Of 17 assessable tumors with EGFR activating mutations, 9 engrafted (53%). Of 3 assessable tumors with ALK-rearrangement, 1 was successful (33%). Conclusion: PDX development of EGFR/ALK+ models for testing with novel therapeutics from various tumor biopsy sites is feasible and will provide valuable realtime information for subsequent treatment decisions in advanced NSCLC patients. Updated engraftment and drug screening data will be presented. Keywords: TKI, Resistance, xenografts, EGFR ALK
Abstracts
S983
Background: The prevalence and clinic pathologic characteristics of MET amplification and overexpression in Chinese patients with non-small cell lung cancer (NSCLC) remain unknown. In this multicenter study, we focus on revealing the frequency and clinic pathological characteristics of MET amplification and explore the predictive value of MET amplification and overexpression status to survival in Chinese NSCLC patients. Methods: MET amplification was detected by fluorescence in-situ hybridization (FISH) in 791 patients with EGFR wild-type samples. MET protein expression was detected by immunohistochemistry. Results: In total, 8 patients were identified as harboring MET amplification from 791 NSCLC patients with EGFR wild-type. Among these 8 patients, one was with histology of adeno-squamous carcinoma and 7 of adenocarcinoma. There was no statistically significant difference among age, gender, smoking status and histologic type between patients with and without MET amplification. MET amplification was more frequent in advanced stage and solid predominant subtype of adenocarcinoma. MET protein expression was performed in 395 patients and 138 were positive. Patients with MET protein expression positive had an inferior overall survival compared to those without MET protein expression (45.0 months vs 65.8 months; P¼0.001). Multivariate analysis revealed that MET expression was independent prognostic factor for poor overall survival (HR¼1.497, P¼0.017), while the MET amplification shows weak relevance for overall survival (HR¼1.974, P¼0.251). Conclusion: MET amplification was rare in Chinese NSCLC without EGFR mutation, with a prevalence of about 1%. MET expression but not amplification could be an independent prognostic factor for shorter OS among those EGFR wild-type NSCLC patients. Keywords: non-small cell lung cancer, MET, amplification, Overexpression
P2.03b-078 MET Gene Amplification and Overexpression in Chinese NSCLC Patients without EGFR Mutations
P2.03b-079 Decreased Expression of miR-125a-3p is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients
Topic: Biomarkers
Topic: Biomarkers
Zhengbo Song,1 Xuzhou Wang,2 Yuhui Zheng,3 Yiping Zhang4 1Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2Department of Pathology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou/China, 3Department of Pathology, fujian Medical University, union Hospital, Fuzhou/China, 4Zhejiang Cancer Hospital, Hangzhou/China
Chunyan Wu,1 Likun Hou2 1Shanghai Pulmonary Hospital Affiliated To Tongji University, Shanghai/China, 2 Department of Pathology Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai/China Background: The microRNA miR-125a-3p is derived from the 3-end of pre-miR-125a, proved associated with
related biopsies. Tumor sufficiency was confirmed prior to implantation into non-obese severe combined immunodeficient (NOD-SCID) mice, with successful engraftment defined as propagation beyond first passage; unsuccessful implantations had no palpable tumor after 6 months. Results: 72/82 (88%) approached patients consented; 49/72 (68%) had adequate tumor tissue for implantation (71% stage III/IV): 46 adenocarcinomas, 2 squamous cell carcinoma, 1 LCNEC. 36/49 (73%) were lifetime never smokers. Patients received adjuvant chemotherapy (3), TKI therapy (15), both (5), or no treatment (26) prior to sampling. Tumor samples were taken from surgically resected lung (18), metastatic adrenal (1) and brain (2), CT-guided lung biopsies (5), endoscopic ultrasoundguided (EBUS) biopsies (6), and thoracentesis pleural fluid (17) specimens. Twenty-eight implanted tumors were EGFR+ (12 exon19 deletions, 2 exon19 deletion/ T790M, 1 exon19 del/exon18 mutation, 12 L858R, and 1 L858R/T790M); 7 had ALK-rearrangements, and 1 had ROS1-rearrangement. Engraftment rates of 31 assessable implanted tumors were as follows: lung resections 12/12 (100%), metastatic resections 2/3 (67%), CT- or EBUSguided biopsies 1/5 (20%), and pleural fluid 2/11 (18%); Engraftment rate was associated with no prior treatment (14/17 no treatment vs 3/14 any treatment, p¼0.001). Of 17 assessable tumors with EGFR activating mutations, 9 engrafted (53%). Of 3 assessable tumors with ALK-rearrangement, 1 was successful (33%). Conclusion: PDX development of EGFR/ALK+ models for testing with novel therapeutics from various tumor biopsy sites is feasible and will provide valuable realtime information for subsequent treatment decisions in advanced NSCLC patients. Updated engraftment and drug screening data will be presented. Keywords: TKI, Resistance, xenografts, EGFR ALK
Abstracts
S983
Background: The prevalence and clinic pathologic characteristics of MET amplification and overexpression in Chinese patients with non-small cell lung cancer (NSCLC) remain unknown. In this multicenter study, we focus on revealing the frequency and clinic pathological characteristics of MET amplification and explore the predictive value of MET amplification and overexpression status to survival in Chinese NSCLC patients. Methods: MET amplification was detected by fluorescence in-situ hybridization (FISH) in 791 patients with EGFR wild-type samples. MET protein expression was detected by immunohistochemistry. Results: In total, 8 patients were identified as harboring MET amplification from 791 NSCLC patients with EGFR wild-type. Among these 8 patients, one was with histology of adeno-squamous carcinoma and 7 of adenocarcinoma. There was no statistically significant difference among age, gender, smoking status and histologic type between patients with and without MET amplification. MET amplification was more frequent in advanced stage and solid predominant subtype of adenocarcinoma. MET protein expression was performed in 395 patients and 138 were positive. Patients with MET protein expression positive had an inferior overall survival compared to those without MET protein expression (45.0 months vs 65.8 months; P¼0.001). Multivariate analysis revealed that MET expression was independent prognostic factor for poor overall survival (HR¼1.497, P¼0.017), while the MET amplification shows weak relevance for overall survival (HR¼1.974, P¼0.251). Conclusion: MET amplification was rare in Chinese NSCLC without EGFR mutation, with a prevalence of about 1%. MET expression but not amplification could be an independent prognostic factor for shorter OS among those EGFR wild-type NSCLC patients. Keywords: non-small cell lung cancer, MET, amplification, Overexpression
P2.03b-078 MET Gene Amplification and Overexpression in Chinese NSCLC Patients without EGFR Mutations
P2.03b-079 Decreased Expression of miR-125a-3p is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients
Topic: Biomarkers
Topic: Biomarkers
Zhengbo Song,1 Xuzhou Wang,2 Yuhui Zheng,3 Yiping Zhang4 1Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2Department of Pathology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou/China, 3Department of Pathology, fujian Medical University, union Hospital, Fuzhou/China, 4Zhejiang Cancer Hospital, Hangzhou/China
Chunyan Wu,1 Likun Hou2 1Shanghai Pulmonary Hospital Affiliated To Tongji University, Shanghai/China, 2 Department of Pathology Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai/China Background: The microRNA miR-125a-3p is derived from the 3-end of pre-miR-125a, proved associated with