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

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.

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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
  2. An Na Seo MD, PhD
  3. So Yeon Park MD, PhD
  4. Joo Young Kim MD
  5. Ji Young Park MD, PhD
  6. Jong Han Yu MD, PhD
  7. Jin-Hee Ahn MD, PhD
  8. Gyungyub Gong MD, PhD

Corresponding author

Correspondence toHee Jin Lee MD, PhD.

Additional information

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

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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

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