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FGFR1 gene amplification in squamous cell carcinomas of the lung: a potential favorable prognostic marker for women and for patients with advanced cancer.
Virchows Arch. 2018 May; 472(5):759-769.VA

Abstract

In squamous cell carcinoma (SCC) of the lung, mutations within the genes of fibroblast growth factor receptors (FGFR) such as K660N/K660E in FGFR2 and R248C/S249C in FGFR3 and FGFR1 gene amplification have been described, but their prognostic relevance still remains unclear. In order to detect the mutation frequencies and to define their prognostic value for associated clinicopathologic features and survival of patients, resected ΔNp63/p40-positive SCC of the lung (n = 101) were screened for FGFR1 gene amplification by fluorescence in situ hybridization performed on formalin-fixed paraffin embedded tissues and for the presumed driver mutations in genes of FGFR2 and FGFR3 by PCR and Sanger sequencing. Twenty-two of 101 SCCs (22%) were positive for amplification based on a FGFR1/centromere (chromosome 8) ratio > 2.0 or higher. In advanced tumor stages (III-IV), the overall survival of patients carrying FGFR1 gene amplification was significantly higher (p = 0.006). Among women, FGFR1 gene amplification was significantly associated with longer overall survival (p = 0.023). The presence of FGFR1 gene amplification was associated with patient age (65 versus 69 years, p = 0.046), but not with gender, tumor stage, histologic subtype, tumor grade, or ΔNp63/p40 immunoreactivity. The S249C mutation in the FGFR3 gene was identified in one out of 101 SCCs (1%); the K600N, K660E, or R248C mutations were not identified. These results suggest that FGFR1 gene amplification is a frequent alteration in SCC of the lung and appears not to be a negative but rather a favorable prognostic marker for women and particularly for patients with advanced SCC of the lung (stage III-IV).

Authors+Show Affiliations

Department of Pathology, Saarland University Medical Center, Homburg, Building 26, 66421, Homburg, Germany. Fidelis.Flockerzi@uks.eu.Department of Pathology, Saarland University Medical Center, Homburg, Building 26, 66421, Homburg, Germany. Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Tübingen, Germany.Department of Thoracic and Cardiovascular Surgery, Saarland University Medical Center, Homburg, Germany.Saarland Cancer Registry, Saarbrücken, Germany.Department of Pathology, Saarland University Medical Center, Homburg, Building 26, 66421, Homburg, Germany. Cancer Center Saarland, Saarland University Medical Center, Homburg, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29270870

Citation

Flockerzi, Fidelis Andrea, et al. "FGFR1 Gene Amplification in Squamous Cell Carcinomas of the Lung: a Potential Favorable Prognostic Marker for Women and for Patients With Advanced Cancer." Virchows Archiv : an International Journal of Pathology, vol. 472, no. 5, 2018, pp. 759-769.
Flockerzi FA, Roggia C, Langer F, et al. FGFR1 gene amplification in squamous cell carcinomas of the lung: a potential favorable prognostic marker for women and for patients with advanced cancer. Virchows Arch. 2018;472(5):759-769.
Flockerzi, F. A., Roggia, C., Langer, F., Holleczek, B., & Bohle, R. M. (2018). FGFR1 gene amplification in squamous cell carcinomas of the lung: a potential favorable prognostic marker for women and for patients with advanced cancer. Virchows Archiv : an International Journal of Pathology, 472(5), 759-769. https://doi.org/10.1007/s00428-017-2282-0
Flockerzi FA, et al. FGFR1 Gene Amplification in Squamous Cell Carcinomas of the Lung: a Potential Favorable Prognostic Marker for Women and for Patients With Advanced Cancer. Virchows Arch. 2018;472(5):759-769. PubMed PMID: 29270870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FGFR1 gene amplification in squamous cell carcinomas of the lung: a potential favorable prognostic marker for women and for patients with advanced cancer. AU - Flockerzi,Fidelis Andrea, AU - Roggia,Cristiana, AU - Langer,Frank, AU - Holleczek,Bernd, AU - Bohle,Rainer M, Y1 - 2017/12/21/ PY - 2017/09/27/received PY - 2017/12/11/accepted PY - 2017/11/30/revised PY - 2017/12/23/pubmed PY - 2018/5/31/medline PY - 2017/12/23/entrez KW - Advanced cancer KW - FGFR1 KW - Non-small cell lung cancer KW - Prognosis KW - Squamous cell carcinoma of the lung KW - Women SP - 759 EP - 769 JF - Virchows Archiv : an international journal of pathology JO - Virchows Arch. VL - 472 IS - 5 N2 - In squamous cell carcinoma (SCC) of the lung, mutations within the genes of fibroblast growth factor receptors (FGFR) such as K660N/K660E in FGFR2 and R248C/S249C in FGFR3 and FGFR1 gene amplification have been described, but their prognostic relevance still remains unclear. In order to detect the mutation frequencies and to define their prognostic value for associated clinicopathologic features and survival of patients, resected ΔNp63/p40-positive SCC of the lung (n = 101) were screened for FGFR1 gene amplification by fluorescence in situ hybridization performed on formalin-fixed paraffin embedded tissues and for the presumed driver mutations in genes of FGFR2 and FGFR3 by PCR and Sanger sequencing. Twenty-two of 101 SCCs (22%) were positive for amplification based on a FGFR1/centromere (chromosome 8) ratio > 2.0 or higher. In advanced tumor stages (III-IV), the overall survival of patients carrying FGFR1 gene amplification was significantly higher (p = 0.006). Among women, FGFR1 gene amplification was significantly associated with longer overall survival (p = 0.023). The presence of FGFR1 gene amplification was associated with patient age (65 versus 69 years, p = 0.046), but not with gender, tumor stage, histologic subtype, tumor grade, or ΔNp63/p40 immunoreactivity. The S249C mutation in the FGFR3 gene was identified in one out of 101 SCCs (1%); the K600N, K660E, or R248C mutations were not identified. These results suggest that FGFR1 gene amplification is a frequent alteration in SCC of the lung and appears not to be a negative but rather a favorable prognostic marker for women and particularly for patients with advanced SCC of the lung (stage III-IV). SN - 1432-2307 UR - https://www.unboundmedicine.com/medline/citation/29270870/FGFR1_gene_amplification_in_squamous_cell_carcinomas_of_the_lung:_a_potential_favorable_prognostic_marker_for_women_and_for_patients_with_advanced_cancer_ L2 - https://dx.doi.org/10.1007/s00428-017-2282-0 DB - PRIME DP - Unbound Medicine ER -