Kenneth J Craddock1, Olga Ludkovski, Jenna Sykes, Frances A Shepherd, Ming-Sound Tsao. 1. *Departments of Pathology, †Ontario Cancer Institute, ‡Department of Biostatistics, §Division of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; and ¶Departments of Laboratory Medicine and Pathobiology, ‖Medicine, University of Toronto, Ontario, Canada.
Abstract
INTRODUCTION: Fibroblast growth factor receptor 1 (FGFR1) gene amplification was recently reported as a recurrent abnormality in 10% to 20% of primary lung squamous cell carcinomas (SqCCs), and has attracted significant interest as a potential therapeutic target. Limited data are available for its prognostic impact in early-stage SqCC. METHODS: Tissue microarrays containing 135 primary lung SqCCs and 58 matching lymph node metastases were tested by interphase fluorescence in situ hybridization for DNA copy number (CN) abnormalities at the 8p12 region including FGFR1. RESULTS: FGFR1amplification was found in 18.2% (22 of 121 evaluable) of primary SqCC, using a definition of average copies of FGFR1 per cell of 5.0 or more. Concordance rate between primaries and matching lymph node metastases was 97.7% (43 of 44; 7 amplified and 37 nonamplified), with the only discordant case showing CN at approximately the dichotomous cutoff. Similarly, concordance between two separate lymph node metastases in each of 10 patients was 100% (1 amplified and 9 nonamplified). Using various CN cutoffs, we found no statistically significant association between FGFR1 CN abnormalities and patient age, sex, tumor grade, stage, smoking status, disease-free survival, cause-specific survival, or overall survival. CONCLUSION: FGFR1 amplification is not prognostic in resected lung squamous cell carcinoma patients.
INTRODUCTION:Fibroblast growth factor receptor 1 (FGFR1) gene amplification was recently reported as a recurrent abnormality in 10% to 20% of primary lung squamous cell carcinomas (SqCCs), and has attracted significant interest as a potential therapeutic target. Limited data are available for its prognostic impact in early-stage SqCC. METHODS: Tissue microarrays containing 135 primary lung SqCCs and 58 matching lymph node metastases were tested by interphase fluorescence in situ hybridization for DNA copy number (CN) abnormalities at the 8p12 region including FGFR1. RESULTS: FGFR1amplification was found in 18.2% (22 of 121 evaluable) of primary SqCC, using a definition of average copies of FGFR1 per cell of 5.0 or more. Concordance rate between primaries and matching lymph node metastases was 97.7% (43 of 44; 7 amplified and 37 nonamplified), with the only discordant case showing CN at approximately the dichotomous cutoff. Similarly, concordance between two separate lymph node metastases in each of 10 patients was 100% (1 amplified and 9 nonamplified). Using various CN cutoffs, we found no statistically significant association between FGFR1CN abnormalities and patient age, sex, tumor grade, stage, smoking status, disease-free survival, cause-specific survival, or overall survival. CONCLUSION:FGFR1 amplification is not prognostic in resected lung squamous cell carcinomapatients.
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