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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

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).

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Acknowledgements

The authors thank J. Michaely and M. Ertz for excellent technical assistance, J. Schöpe for comments on statistical evaluation, and A. Seibold for editing the manuscript.

Funding

This work was supported by scholarship (Deutschlandstipendium) from Federal Ministry of Education and Research (Germany) to F. A. V. Flockerzi and by the FP7 European projects CHIC (grant no. 600841).

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Correspondence to Fidelis Andrea Flockerzi.

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The authors declare no competing financial interests.

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This study was performed within the FP7-ICT programme (ID number 600841) according with the Declaration of Helsinki and approved by the Ethik Kommission an der Ärztekammer des Saarlandes.

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The authors hereby state that the article is original, presently not under consideration for publication in another journal and has not been published previously except, part of it, in the form of an abstract (Virchows Archiv, European Journal of Pathology, Volume 469 Supplement 1 September 2016).

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Flockerzi, F.A., 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 472, 759–769 (2018). https://doi.org/10.1007/s00428-017-2282-0

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Keywords

  • FGFR1
  • Squamous cell carcinoma of the lung
  • Non-small cell lung cancer
  • Prognosis
  • Women
  • Advanced cancer