title: Low prognostic implication of fibroblast growth factor family activation in triple-negative breast cancer subsets.
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.
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, backlila@gmail.com.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: An Na
authors.initials: AN
authors.lastname: Seo
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Yu
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Gyungyub
authors.initials: G
authors.lastname: Gong
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018276:Carcinoma, Medullary / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D005500:Follow-Up Studies; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000145:classification* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2