Matthias Preusser1, Anna S Berghoff2, Walter Berger3, Aysegül Ilhan-Mutlu1, Carina Dinhof1, Georg Widhalm4, Karin Dieckmann5, Adelheid Wöhrer2, Monika Hackl6, Andreas von Deimling7, Berthold Streubel8, Peter Birner9. 1. Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria. 2. Institute of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria. 3. Institute of Cancer Research, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria. 4. Department of Neurosurgery, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria. 5. Department of Radiotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria. 6. Austrian National Cancer Registry, Statistics Austria, Vienna, Austria. 7. Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, and Clinical Cooperation Unit Neuropathology, DKFZ, Heidelberg, Germany. 8. Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria. 9. Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Vienna, Austria. Electronic address: peter.birner@meduniwien.ac.at.
Abstract
OBJECTIVES: FGFR1 amplifications are common in squamous cell carcinoma and rare in adenocarcinoma of the lung, but have not been investigated in brain metastases of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We performed fluorescent in situ hybridization (FISH) for FGFR1 and immunohistochemistry for pAKT, PI3K, HIF1a and Ki67 in 175 NSCLC brain metastases and 11 matched primary tumors. ALK gene rearrangement status was available from a previous study. We performed statistical correlations of clinical, histopathological and molecular data. RESULTS: FGFR1 amplifications were found in a total of 30/175 (17%) brain metastases: 4/21 (19%) squamous cell carcinomas, 20/130 (15.3%) adenocarcinomas, 2/12 (16.6%) adenosquamous carcinomas, 4/9 (44.4%) large cell carcinomas and 0/3 neuroendocrine large cell carcinoma. FGFR1 gene status was identical between primary tumors and brain metastases in 9/11 evaluable cases. In 2/11 cases (1 adenosquamous and 1 large cell carcinoma), FGFR1 amplifications were present only in the brain metastasis and not in the primary tumor. Furthermore, we found a significant positive correlation of ALK and FGFR1 gene amplification status in brain metastases (p<0.001, Chi square test). Patients with high-level FGFR1 amplifications had significantly higher number of visceral metastases (p<0.001, Chi square test). CONCLUSION: Our findings argue for an enrichment of FGFR1 amplifications in brain metastases of adenocarcinomas (where they were 5-fold more frequent than reported for primary tumors) and possibly also of other non-squamous carcinomas, but not in squamous cell carcinomas of the lung. These results may be relevant for targeted therapy and prophylaxis of NSCLC brain metastases.
OBJECTIVES:FGFR1 amplifications are common in squamous cell carcinoma and rare in adenocarcinoma of the lung, but have not been investigated in brain metastases of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We performed fluorescent in situ hybridization (FISH) for FGFR1 and immunohistochemistry for pAKT, PI3K, HIF1a and Ki67 in 175 NSCLC brain metastases and 11 matched primary tumors. ALK gene rearrangement status was available from a previous study. We performed statistical correlations of clinical, histopathological and molecular data. RESULTS:FGFR1 amplifications were found in a total of 30/175 (17%) brain metastases: 4/21 (19%) squamous cell carcinomas, 20/130 (15.3%) adenocarcinomas, 2/12 (16.6%) adenosquamous carcinomas, 4/9 (44.4%) large cell carcinomas and 0/3 neuroendocrine large cell carcinoma. FGFR1 gene status was identical between primary tumors and brain metastases in 9/11 evaluable cases. In 2/11 cases (1 adenosquamous and 1 large cell carcinoma), FGFR1 amplifications were present only in the brain metastasis and not in the primary tumor. Furthermore, we found a significant positive correlation of ALK and FGFR1 gene amplification status in brain metastases (p<0.001, Chi square test). Patients with high-level FGFR1 amplifications had significantly higher number of visceral metastases (p<0.001, Chi square test). CONCLUSION: Our findings argue for an enrichment of FGFR1 amplifications in brain metastases of adenocarcinomas (where they were 5-fold more frequent than reported for primary tumors) and possibly also of other non-squamous carcinomas, but not in squamous cell carcinomas of the lung. These results may be relevant for targeted therapy and prophylaxis of NSCLC brain metastases.
Authors: Mikkel G Terp; Kirstine Jacobsen; Miguel Angel Molina; Niki Karachaliou; Hans C Beck; Jordi Bertran-Alamillo; Ana Giménez-Capitán; Andrés F Cardona; Rafael Rosell; Henrik J Ditzel Journal: NPJ Precis Oncol Date: 2021-07-15