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Definition of a fluorescence in-situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer.
Mod Pathol. 2012 Nov; 25(11):1473-80.MP

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.

Authors+Show Affiliations

Centre of Integrated Oncology Köln-Bonn, Institute of Pathology, University Hospital Cologne, Cologne, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22684217

Citation

Schildhaus, Hans-Ulrich, et al. "Definition of a Fluorescence In-situ Hybridization Score Identifies High- and Low-level FGFR1 Amplification Types in Squamous Cell Lung Cancer." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 25, no. 11, 2012, pp. 1473-80.
Schildhaus HU, Heukamp LC, Merkelbach-Bruse S, et al. Definition of a fluorescence in-situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer. Mod Pathol. 2012;25(11):1473-80.
Schildhaus, H. U., Heukamp, L. C., Merkelbach-Bruse, S., Riesner, K., Schmitz, K., Binot, E., Paggen, E., Albus, K., Schulte, W., Ko, Y. D., Schlesinger, A., Ansén, S., Engel-Riedel, W., Brockmann, M., Serke, M., Gerigk, U., Huss, S., Göke, F., Perner, S., ... Buettner, R. (2012). Definition of a fluorescence in-situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 25(11), 1473-80. https://doi.org/10.1038/modpathol.2012.102
Schildhaus HU, et al. Definition of a Fluorescence In-situ Hybridization Score Identifies High- and Low-level FGFR1 Amplification Types in Squamous Cell Lung Cancer. Mod Pathol. 2012;25(11):1473-80. PubMed PMID: 22684217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Definition of a fluorescence in-situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer. AU - Schildhaus,Hans-Ulrich, AU - Heukamp,Lukas C, AU - Merkelbach-Bruse,Sabine, AU - Riesner,Katharina, AU - Schmitz,Katja, AU - Binot,Elke, AU - Paggen,Ellen, AU - Albus,Kerstin, AU - Schulte,Wolfgang, AU - Ko,Yon-Dschun, AU - Schlesinger,Andreas, AU - Ansén,Sascha, AU - Engel-Riedel,Walburga, AU - Brockmann,Michael, AU - Serke,Monika, AU - Gerigk,Ulrich, AU - Huss,Sebastian, AU - Göke,Friederike, AU - Perner,Sven, AU - Hekmat,Khosro, AU - Frank,Konrad F, AU - Reiser,Marcel, AU - Schnell,Roland, AU - Bos,Marc, AU - Mattonet,Christian, AU - Sos,Martin, AU - Stoelben,Erich, AU - Wolf,Jürgen, AU - Zander,Thomas, AU - Buettner,Reinhard, Y1 - 2012/06/08/ PY - 2012/6/12/entrez PY - 2012/6/12/pubmed PY - 2013/4/24/medline SP - 1473 EP - 80 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod Pathol VL - 25 IS - 11 N2 - 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. SN - 1530-0285 UR - https://www.unboundmedicine.com/medline/citation/22684217/Definition_of_a_fluorescence_in_situ_hybridization_score_identifies_high__and_low_level_FGFR1_amplification_types_in_squamous_cell_lung_cancer_ L2 - https://doi.org/10.1038/modpathol.2012.102 DB - PRIME DP - Unbound Medicine ER -