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Expression of FGFR1 is an independent prognostic factor in triple-negative breast cancer

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Abstract

Triple-negative breast cancers (TNBCs) are clinically aggressive tumors with limited treatment options. We examined the clinicopathological associations and prognostic implications of FGFR1 and FGFR2 expression in TNBCs. Tissue microarrays constructed from TNBCs were immunostained with FGFR1 and FGFR2, and scored by intensity and percentage of tumor cells stained per intensity for each subcellular compartment, which were correlated with clinicopathological parameters and survival. Cell migration following siRNA-mediated silencing of the FGFR1 gene in TNBC cell lines was also performed. 714 cases were informative for FGFR1 and FGFR2 immunostaining. Thresholds were defined as at least 1 % of cells stained and H-score of 100 or more. Proportions positive by each threshold were, respectively, 89.9 %, 7.1 % for FGFR1 (cytoplasm); 36.8 %, 7.8 % for FGFR2 (cytoplasm); and 33.5 %, 5.2 % for FGFR2 (membrane). Significant associations included FGFR1 and FGFR2 immunostaining for lobular subtype, FGFR2 immunostaining with lower grade, and more basal-like cancers with H-scores of 100 or more FGFR1 immunostaining. Multivariate Cox regression analysis showed FGFR1 expression in TNBCs to be independently prognostic for overall survival (OS) at both thresholds. Cases completely negative (less than 1 % staining) for FGFR1 immunostaining showed improved OS, while those with H-score of 100 or more immunostaining had the worst OS. Cell line studies revealed up-regulation of the FGFR1 gene in the MDA-MB-231 and Hs578T TNBC cells, and specific knockdown of FGFR1 expression significantly reduced cell migration in MDA-MB-231 cell line. In conclusion, FGFR1 expression in TNBCs is independently prognostic of OS, and H-score of 100 or more FGFR1 immunostaining may define tumors that have treatment potential via FGFR signaling inhibition.

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Acknowledgments

The current project is part of a study approved by the Singhealth Institutional Review Board (CIRB Ref: 2011/433/B). For this type of study, formal consent is not required. This study was funded by Stratified Medicine Office (Grant No. SMP0201302).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore

    Chee Leong Cheng, Aye Aye Thike, Sie Yong Jane Tan & Puay Hoon Tan

  2. Department of Anatomy, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, MD10, 4 Medical Drive, #03-01, Singapore, 117597, Singapore

    Pei Jou Chua & Boon Huat Bay

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  1. Chee Leong Cheng
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  2. Aye Aye Thike
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Correspondence to Chee Leong Cheng.

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Cheng, C.L., Thike, A.A., Tan, S.Y.J. et al. Expression of FGFR1 is an independent prognostic factor in triple-negative breast cancer. Breast Cancer Res Treat 151, 99–111 (2015). https://doi.org/10.1007/s10549-015-3371-x

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  • DOI: https://doi.org/10.1007/s10549-015-3371-x

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