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Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH.
Mod Pathol. 2014 Dec; 27(12):1621-31.MP

Abstract

The aim of this study was to investigate the prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification by fluorescence in situ hybridization (FISH) in a lung cancer patient cohort and to correlate results with morphology, silver in situ hybridization (SISH), and patient outcome. FGFR1 FISH and SISH were performed in 406 and 385 lung cancer cases, respectively, and the results were compared. High-level FGFR1 amplification was defined as the ratio of FGFR1/centromere 8 ≥2, or tumor cell percentage with ≥15 signals ≥10%, or average number of signals/tumor cell nucleus ≥6. Low-level amplification was defined as tumor cell percentage with ≥5 signals ≥50%. Of 406 tumors tested, there were 191 squamous cell carcinomas, 28 carcinomas with focal squamous morphology, 24 large cell carcinomas with squamous immunoprofile, 115 adenocarcinomas, 17 neuroendocrine tumors, and 31 carcinomas without squamous morphology or immunoprofile. FGFR1 FISH was assessable in 368 tumors, with FGFR1 amplification identified in 50, including 48 tumors with either squamous morphology or immunoprofile (48 of 225, 21.3%), and two 'marker-null' tumors without squamous or glandular morphology or immunoprofile (2 of 143, 1.4%; P<0.0001). FGFR1 SISH was assessable in 347 tumors. All 46 FGFR1 FISH-amplified tumors with tumor available for testing showed amplification with SISH, while all other tumors were negative. There was no relationship between FGFR1 amplification status and disease-free (P=0.88, HR=1.04, 95% confidence interval (CI)=0.67-1.60) or overall survival (P=0.97, HR=1.01, 95% CI=0.65-1.58) in surgically radically treated patients with tumors with any squamous morphology or immunoprofile. FGFR1 amplification is a common abnormality in tumors with any squamous morphology or immunoprofile, but it is also present in 'marker-null' tumors. The results of FGFR1 SISH showed 1:1 correlation with the results of FGFR1 FISH, indicating that SISH may be an alternative method to detect FGFR1 amplification. No relationship was detected between patient outcome and FGFR1 amplification.

Authors+Show Affiliations

Department of Anatomical Pathology, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.Department of Anatomical Pathology, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.Research Division, Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Victoria, Australia.Department of Respiratory and Sleep Medicine, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.Department of Surgery, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.Department of Thoracic Surgery, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.1] Research Division, Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Victoria, Australia [2] Division of Hematology and Medical Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.Department of Thoracic Surgery, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.

Pub Type(s)

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

Language

eng

PubMed ID

24762544

Citation

Russell, Prudence A., et al. "Prevalence, Morphology, and Natural History of FGFR1-amplified Lung Cancer, Including Squamous Cell Carcinoma, Detected By FISH and SISH." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 27, no. 12, 2014, pp. 1621-31.
Russell PA, Yu Y, Young RJ, et al. Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH. Mod Pathol. 2014;27(12):1621-31.
Russell, P. A., Yu, Y., Young, R. J., Conron, M., Wainer, Z., Alam, N., Solomon, B., & Wright, G. M. (2014). Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 27(12), 1621-31. https://doi.org/10.1038/modpathol.2014.71
Russell PA, et al. Prevalence, Morphology, and Natural History of FGFR1-amplified Lung Cancer, Including Squamous Cell Carcinoma, Detected By FISH and SISH. Mod Pathol. 2014;27(12):1621-31. PubMed PMID: 24762544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH. AU - Russell,Prudence A, AU - Yu,Yong, AU - Young,Richard J, AU - Conron,Matthew, AU - Wainer,Zoe, AU - Alam,Naveed, AU - Solomon,Benjamin, AU - Wright,Gavin M, Y1 - 2014/04/25/ PY - 2013/09/23/received PY - 2014/03/26/revised PY - 2014/03/26/accepted PY - 2014/4/26/entrez PY - 2014/4/26/pubmed PY - 2015/8/5/medline SP - 1621 EP - 31 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod Pathol VL - 27 IS - 12 N2 - The aim of this study was to investigate the prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification by fluorescence in situ hybridization (FISH) in a lung cancer patient cohort and to correlate results with morphology, silver in situ hybridization (SISH), and patient outcome. FGFR1 FISH and SISH were performed in 406 and 385 lung cancer cases, respectively, and the results were compared. High-level FGFR1 amplification was defined as the ratio of FGFR1/centromere 8 ≥2, or tumor cell percentage with ≥15 signals ≥10%, or average number of signals/tumor cell nucleus ≥6. Low-level amplification was defined as tumor cell percentage with ≥5 signals ≥50%. Of 406 tumors tested, there were 191 squamous cell carcinomas, 28 carcinomas with focal squamous morphology, 24 large cell carcinomas with squamous immunoprofile, 115 adenocarcinomas, 17 neuroendocrine tumors, and 31 carcinomas without squamous morphology or immunoprofile. FGFR1 FISH was assessable in 368 tumors, with FGFR1 amplification identified in 50, including 48 tumors with either squamous morphology or immunoprofile (48 of 225, 21.3%), and two 'marker-null' tumors without squamous or glandular morphology or immunoprofile (2 of 143, 1.4%; P<0.0001). FGFR1 SISH was assessable in 347 tumors. All 46 FGFR1 FISH-amplified tumors with tumor available for testing showed amplification with SISH, while all other tumors were negative. There was no relationship between FGFR1 amplification status and disease-free (P=0.88, HR=1.04, 95% confidence interval (CI)=0.67-1.60) or overall survival (P=0.97, HR=1.01, 95% CI=0.65-1.58) in surgically radically treated patients with tumors with any squamous morphology or immunoprofile. FGFR1 amplification is a common abnormality in tumors with any squamous morphology or immunoprofile, but it is also present in 'marker-null' tumors. The results of FGFR1 SISH showed 1:1 correlation with the results of FGFR1 FISH, indicating that SISH may be an alternative method to detect FGFR1 amplification. No relationship was detected between patient outcome and FGFR1 amplification. SN - 1530-0285 UR - https://www.unboundmedicine.com/medline/citation/24762544/Prevalence_morphology_and_natural_history_of_FGFR1_amplified_lung_cancer_including_squamous_cell_carcinoma_detected_by_FISH_and_SISH_ L2 - https://doi.org/10.1038/modpathol.2014.71 DB - PRIME DP - Unbound Medicine ER -