Schildhaus, Hans-Ulrich, Heukamp, Lukas C., Merkelbach-Bruse, Sabine, Riesner, Katharina, Schmitz, Katja, Binot, Elke, Paggen, Ellen, Albus, Kerstin, Schulte, Wolfgang, Ko, Yon-Dschun, Schlesinger, Andreas, Ansen, Sascha, Engel-Riedel, Walburga, Brockmann, Michael, Serke, Monika, Gerigk, Ulrich, Huss, Sebastian, Goeke, Friederike, Perner, Sven, Hekmat, Khosro, Frank, Konrad F., Reiser, Marcel, Schnell, Roland, Bos, Marc, Mattonet, Christian, Sos, Martin, Stoelben, Erich, Wolf, Juergen, Zander, Thomas and Buettner, Reinhard (2012). Definition of a fluorescence in-situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer. Mod. Pathol., 25 (11). S. 1473 - 1481. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1530-0285

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Abstract

We recently reported fibroblast growth factor receptor-type 1 (FGFR1) amplification to be associated with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. This makes FGFR1 a novel target for directed therapy in these tumors. To reproducibly identify patients for clinical studies, we developed a standardized reading and evaluation strategy for FGFR1 fluorescence in-situ hybridization (FISH) and propose evaluation criteria, describe different patterns of low- and high-level amplifications and report on the prevalence of FGFR1 amplifications in pulmonary carcinomas. A total of 420 lung cancer patients including 307 squamous carcinomas, 100 adenocarcinomas of the lung and 13 carcinomas of other types were analyzed for FGFR1 amplification using a dual color FISH. We found heterogeneous and different patterns of gene copy numbers. FGFR1 amplifications were observed in 20% of pulmonary squamous carcinomas but not in adenocarcinomas. High-level amplification (as defined by an FGFR1/centromer 8 (CEN8) ratio >= 2.0, or average number of FGFR1 signals per tumor cell nucleus >= 6, or the percentage of tumor cells containing >= 15 FGFR1 signals or large clusters >= 10%) was detected at a frequency of 16% and low-level amplification (as defined by >= 5 FGFR1 signals in >= 50% of tumor cells) at a frequency of 4%. We conclude that FGFR1 amplification is one of the most frequent therapeutically tractable genetic lesions in pulmonary carcinomas. Standardized reporting of FGFR1 amplification in squamous carcinomas of the lung will become increasingly important to correlate therapeutic responses with FGFR1 inhibitors in clinical studies. Thus, our reading and evaluation strategy might serve as a basis for identifying patients for ongoing and upcoming clinical trials. Modern Pathology (2012) 25, 1473-1480; doi: 10.1038/modpathol.2012.102; published online 8 June 2012

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schildhaus, Hans-UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heukamp, Lukas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merkelbach-Bruse, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riesner, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmitz, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Binot, ElkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paggen, EllenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Albus, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulte, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ko, Yon-DschunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlesinger, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ansen, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engel-Riedel, WalburgaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brockmann, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Serke, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerigk, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huss, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goeke, FriederikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perner, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hekmat, KhosroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frank, Konrad F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reiser, MarcelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schnell, RolandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bos, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mattonet, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sos, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoelben, ErichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-479791
DOI: 10.1038/modpathol.2012.102
Journal or Publication Title: Mod. Pathol.
Volume: 25
Number: 11
Page Range: S. 1473 - 1481
Date: 2012
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1530-0285
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
THERAPEUTIC TARGET; CARCINOMAS; SURVIVAL; GENEMultiple languages
PathologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47979

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