Friederike Göke1, Alina Franzen1, Roopika Menon1, Diane Goltz2, Robert Kirsten3, Diana Boehm3, Wenzel Vogel3, Antonia Göke3, Veit Scheble4, Joerg Ellinger5, Ulrich Gerigk6, Falko Fend7, Patrick Wagner8, Andreas Schroeck9, Sven Perner10. 1. Institute of Pathology, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany; Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany. 2. Institute of Pathology, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany. 3. Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany. 4. Department of Hematology and Oncology, University Hospital of Tuebingen, Tuebingen, Germany. 5. Department of Urology, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany. 6. Department of Thorax Surgery, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany. 7. Institute of Pathology, University Hospital of Tuebingen, Tuebingen, Germany. 8. Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA. 9. Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany; Department of Head and Neck Surgery, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany. 10. Institute of Pathology, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany; Institute of Prostate Cancer Research, Affiliated Malteser Hospital, University Hospital of Bonn, Bonn, Germany. Electronic address: sven.perner1972@gmail.com.
Abstract
BACKGROUND: We previously identified amplification of the fibroblast growth factor receptor 1 gene (FGFR1) as a potential therapeutic target for small-molecule inhibitor therapy in squamous cell lung cancer (L-SCC). Currently, clinical phase I trials are underway to examine whether patients with FGFR1-amplified L-SCC benefit from a targeted therapy approach using small-molecule inhibitors. Because most patients with lung cancer present with metastatic disease, we investigated whether lymph node metastases in L-SCC share the FGFR1 amplification status of their corresponding primary tumor. METHODS: The study cohort consisted of 72 patients with L-SCC, 39 with regional lymph node metastases. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tissue of the primary tumors and, where present, of the corresponding lymph node metastasis. A biotin-labeled target probe spanning the FGFR1 locus (8p11.22-23) was used to determine the FGFR1 amplification status by fluorescence in situ hybridization. RESULTS: FGFR1 amplification was detected in 16% (12 of 72) of all primary L-SCCs. In metastatic tumors, 18% (seven of 39) of the lymph node metastases displayed FGFR1 amplification with an exact correlation of FGFR1 amplification status between tumor and metastatic tissue. CONCLUSIONS: FGFR1 amplification is a common genetic event occurring at a frequency of 16% in L-SCCs. Moreover, lymph node metastases derived from FGFR1-amplified L-SCCs also exhibit FGFR1 amplification. Therefore, we suggest that the FGFR1 amplification is a clonal event in tumor progression. Beyond this biologically relevant observation, the findings carry potential therapeutic implications in that small-molecule inhibitors may be applicable to the treatment of a subset of patients with metastatic L-SCC.
BACKGROUND: We previously identified amplification of the fibroblast growth factor receptor 1 gene (FGFR1) as a potential therapeutic target for small-molecule inhibitor therapy in squamous cell lung cancer (L-SCC). Currently, clinical phase I trials are underway to examine whether patients with FGFR1-amplified L-SCC benefit from a targeted therapy approach using small-molecule inhibitors. Because most patients with lung cancer present with metastatic disease, we investigated whether lymph node metastases in L-SCC share the FGFR1 amplification status of their corresponding primary tumor. METHODS: The study cohort consisted of 72 patients with L-SCC, 39 with regional lymph node metastases. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tissue of the primary tumors and, where present, of the corresponding lymph node metastasis. A biotin-labeled target probe spanning the FGFR1 locus (8p11.22-23) was used to determine the FGFR1 amplification status by fluorescence in situ hybridization. RESULTS:FGFR1 amplification was detected in 16% (12 of 72) of all primary L-SCCs. In metastatic tumors, 18% (seven of 39) of the lymph node metastases displayed FGFR1 amplification with an exact correlation of FGFR1 amplification status between tumor and metastatic tissue. CONCLUSIONS:FGFR1 amplification is a common genetic event occurring at a frequency of 16% in L-SCCs. Moreover, lymph node metastases derived from FGFR1-amplified L-SCCs also exhibit FGFR1 amplification. Therefore, we suggest that the FGFR1 amplification is a clonal event in tumor progression. Beyond this biologically relevant observation, the findings carry potential therapeutic implications in that small-molecule inhibitors may be applicable to the treatment of a subset of patients with metastatic L-SCC.
Authors: Grace K Dy; Sumithra J Mandrekar; Garth D Nelson; Jeffrey P Meyers; Araba A Adjei; Helen J Ross; Rafat H Ansari; Alan P Lyss; Philip J Stella; Steven E Schild; Julian R Molina; Alex A Adjei Journal: J Thorac Oncol Date: 2013-01 Impact factor: 15.609
Authors: Murry W Wynes; Trista K Hinz; Dexiang Gao; Michael Martini; Lindsay A Marek; Kathryn E Ware; Michael G Edwards; Diana Böhm; Sven Perner; Barbara A Helfrich; Rafal Dziadziuszko; Jacek Jassem; Szymon Wojtylak; Aleksandra Sejda; Joseph M Gozgit; Paul A Bunn; D Ross Camidge; Aik-Choon Tan; Fred R Hirsch; Lynn E Heasley Journal: Clin Cancer Res Date: 2014-04-25 Impact factor: 12.531
Authors: Vitor Sousa; Diana Reis; Maria Silva; Ana Maria Alarcão; Ana Filipa Ladeirinha; Maria João d'Aguiar; Teresa Ferreira; Sandra Caramujo-Balseiro; Lina Carvalho Journal: Virchows Arch Date: 2016-05-19 Impact factor: 4.064