Rationale for Treatment of Metastatic Squamous Cell Carcinoma of the Lung Using FGFR1 Inhibitors
Friederike Goeke, Alina Franzen, Roopika Mennon, Veit Scheble, Diane Goltz, Robert Kirsten, Diana Boehm, Wenzel Vogel, Andreas Schroeck, Sven Perner. University Hospital Bonn, Bonn, Germany; University Hospital Tuebingen, Tuebingen, Germany
Background: We previously identified amplification of the fibroblast growth factor receptor 1 (FGFR1) gene as a potential therapeutic target for a small molecule inhibitor therapy in squamous cell lung cancer (L-SCC). Currently, clinical phase 1 trials are running in order to test if patients with FGFR1-amplified L-SCC benefit from a targeted therapy using small molecule inhibitors against FGFR. As most lung cancer patients present with metastatic disease, we investigated if the FGFR1 amplification also occurs in lymph node metastatic tissue of FGFR1-amplified and non-amplified primary tumors. Our study aims to give a rational whether to include patients with a metastatic L-SCC in a targeted small molecule inhibitor therapy.
Design: Our study cohort consists of 72 patients suffering from L-SCC. Of these, 39 patients presented with regional lymph node metastasis. 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-labelled target probe spanning the FGFR1 locus (8p11.22-23) was used to determine the FGFR1 amplification status by fluorescence in-situ hybridization (FISH).
Results: 16% (12/72) of all primary tumors and 18% (7/39) of the lymph node metastasis displayed a FGFR1 amplification. Of interest, FGFR1 lymph node metastasis developed from FGFR1 amplified primary tumors. Furthermore, non-amplified tumors never displayed FGFR1 amplification in their corresponding lymph node metastases.
Conclusions: We could confirm that the FGFR1 amplification is a common genetic event in L-SCC. On top of that, we are the first to discover FGFR1 amplification in lymph node metastasis. Interestingly, the FGFR1 amplification status always transfers from primary L-SCC into the corresponding lymph node metastasis. Therefore, we suggest that the FGFR1 amplification is a clonal event in tumor progression. Beyond this biologically relevant observation, our finding is the basis for a rational of treating patients suffering not only from primary but also from metastatic FGFR1 amplified L-SCC with a targeted small molecule inhibitor therapy using FGFR inhibitors.
Monday, March 19, 2012 2:15 PM
Platform Session: Section D, Monday Afternoon