Skip to main content

Advertisement

SpringerLink
Log in

Low Prognostic Implication of Fibroblast Growth Factor Family Activation in Triple-negative Breast Cancer Subsets

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Despite a greater understanding of the molecular heterogeneity of breast cancer, current therapeutic strategies still cannot overcome the relatively poor prognosis of triple-negative breast cancer (TNBC). Deregulation of fibroblast growth factor (FGF) signaling has been found in breast cancer, and blocking this pathway has been suggested as a potential therapeutic target. We therefore evaluated the expression and copy number changes of FGF family members in TNBC.

Methods

We retrospectively evaluated 148 primary TNBC in 2009 for FGFR1, FGFR2, and FGF2 expression by immunohistochemistry. FGFR1 and FGFR2 gene copy numbers were analyzed by fluorescence in situ hybridization. The Cancer Genome Atlas (TCGA) data was used to study correlations between gene expression and amplification or methylation of FGFR1, FGFR2, and FGF2 in basal-like TNBC.

Results

FGFR1, FGFR2, and FGF2 expression were found in 16.2 % (24 of 148), 12.8 % (19 of 148), and 12.8 % (19 of 148) of TNBCs, respectively. FGFR1 gene amplification was observed in 4.1 % (6 of 145), and FGFR1 high polysomy was detected in 6.9 % (10 of 145) of the cases examined. FGFR2 gene amplification and high polysomy were identified in 4.7 % (6 of 129 cases) and 0.8 % (1 of 129 cases), respectively. FGF2 expression was found to be associated with basal-like TNBC. The expression of FGF family members and FGFR1 or FGFR2 gene amplification did not affect patient survival. TCGA data revealed that promoter methylation of the 3 genes was significantly associated with mRNA expression.

Conclusions

Even though the implications for patient outcomes are not significant, subsets of TNBCs harbor FGFR1 or FGFR2 gene amplification and FGFR1, FGFR2, or FGF2 protein overexpression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121:2750–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Ossovskaya V, Wang Y, Budoff A, Xu Q, Lituev A, Potapova O, et al. Exploring molecular pathways of triple-negative breast cancer. Genes Cancer. 2011;2:870–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Turner N, Lambros MB, Horlings HM, Pearson A, Sharpe R, Natrajan R, et al. Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets. Oncogene. 2010;29:2013–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Brooks AN, Kilgour E, Smith PD. Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancer. Clin Cancer Res. 2012;18:1855–62.

    Article  CAS  PubMed  Google Scholar 

  5. Ahmad I, Iwata T, Leung HY. Mechanisms of FGFR-mediated carcinogenesis. Biochim Biophys Acta. 2012;1823:850–60.

    Article  CAS  PubMed  Google Scholar 

  6. Elbauomy Elsheikh S, Green AR, Lambros MB, Turner NC, Grainge MJ, Powe D, et al. FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis. Breast Cancer Res. 2007;9:R23.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28:2784–95.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Koh YW, Lee HJ, Lee JW, Kang J, Gong G. Dual-color silver-enhanced in situ hybridization for assessing HER2 gene amplification in breast cancer. Mod Pathol. 2011;24:794–800.

    Article  CAS  PubMed  Google Scholar 

  9. Jang MH, Kim EJ, Choi Y, Lee HE, Kim YJ, Kim JH, et al. FGFR1 is amplified during the progression of in situ to invasive breast carcinoma. Breast Cancer Res. 2012;14:R115.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Cappuzzo F, Hirsch FR, Rossi E, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst. 2005;97:643-55.

    Article  CAS  PubMed  Google Scholar 

  11. Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, et al. The landscape of cancer genes and mutational processes in breast cancer. Nature. 2012;486:400–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.

    Article  CAS  PubMed  Google Scholar 

  13. Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008;14:1368–76.

    Article  CAS  PubMed  Google Scholar 

  14. Beroukhim R, Getz G, Nghiemphu L, Barretina J, Hsueh T, Linhart D, et al. Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci USA. 2007;104:20007–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Massabeau C, Sigal-Zafrani B, Belin L, Savignoni A, Richardson M, Kirova YM, et al. The fibroblast growth factor receptor 1 (FGFR1), a marker of response to chemoradiotherapy in breast cancer? Breast Cancer Res Treat. 2012;134:259–66.

    Article  CAS  PubMed  Google Scholar 

  16. Sun S, Jiang Y, Zhang G, Song H, Zhang X, Zhang Y, et al. Increased expression of fibroblastic growth factor receptor 2 is correlated with poor prognosis in patients with breast cancer. J Surg Oncol. 2012;105:773–9.

    Article  CAS  PubMed  Google Scholar 

  17. Gelsi-Boyer V, Orsetti B, Cervera N, Finetti P, Sircoulomb F, Rougé C, et al. Comprehensive profiling of 8p11-12 amplification in breast cancer. Mol Cancer Res. 2005;3:655–67.

    Article  CAS  PubMed  Google Scholar 

  18. Turner N, Pearson A, Sharpe R, Lambros M, Geyer F, Lopez-Garcia MA, et al. FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer. Cancer Res. 2010;70:2085–94.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Sharpe R, Pearson A, Herrera-Abreu MT, Johnson D, Mackay A, Welti JC, et al. FGFR signaling promotes the growth of triple-negative and basal-like breast cancer cell lines both in vitro and in vivo. Clin Cancer Res. 2011;17:5275–86.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Jain VK, Turner NC. Challenges and opportunities in the targeting of fibroblast growth factor receptors in breast cancer. Breast Cancer Res. 2012;14:208.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Michor F, Polyak K. The origins and implications of intratumor heterogeneity. Cancer Prev Res Phila. 2010;3:1361–4.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Hee Jin Lee MD, PhD, Joo Young Kim MD, Ji Young Park MD, PhD & Gyungyub Gong MD, PhD

  2. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea

    An Na Seo MD, PhD & So Yeon Park MD, PhD

  3. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea

    So Yeon Park MD, PhD

  4. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Jong Han Yu MD, PhD

  5. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Jin-Hee Ahn MD, PhD

Authors
  1. Hee Jin Lee MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. An Na Seo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. So Yeon Park MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joo Young Kim MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ji Young Park MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jong Han Yu MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jin-Hee Ahn MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gyungyub Gong MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hee Jin Lee MD, PhD.

Additional information

Hee Jin Lee and An Na Seo are contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, H.J., Seo, A.N., Park, S.Y. et al. Low Prognostic Implication of Fibroblast Growth Factor Family Activation in Triple-negative Breast Cancer Subsets. Ann Surg Oncol 21, 1561–1568 (2014). https://doi.org/10.1245/s10434-013-3456-x

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-013-3456-x

Keywords

Search

Navigation