Low prognostic implication of fibroblast growth factor family activation in triple-negative breast cancer subsets
Hee Jin Lee1, An Na Seo, So Yeon Park
1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, backlila@gmail.com.
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.
Insights
Subsets of triple-negative breast cancer (TNBC) show fibroblast growth factor receptor (FGFR) gene amplification or protein overexpression. These alterations, however, did not significantly impact patient survival in this study.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) has a poor prognosis despite advances in understanding its molecular heterogeneity.
- Fibroblast growth factor (FGF) signaling pathway deregulation is implicated in breast cancer.
- Targeting the FGF pathway is a potential therapeutic strategy for TNBC.
Purpose of the Study:
- To evaluate the expression and copy number alterations of FGF family members in TNBC.
- To investigate the correlation between gene expression, amplification, and methylation of FGFR1, FGFR2, and FGF2 in basal-like TNBC using TCGA data.
Main Methods:
- Retrospective analysis of 148 primary TNBC cases from 2009.
- Immunohistochemistry used to assess FGFR1, FGFR2, and FGF2 expression.
- Fluorescence in situ hybridization for FGFR1 and FGFR2 gene copy number analysis.
- TCGA data utilized for correlation studies.
Main Results:
- FGFR1, FGFR2, and FGF2 protein expression detected in 16.2%, 12.8%, and 12.8% of TNBCs, respectively.
- FGFR1 gene amplification/polysomy found in 11% of cases; FGFR2 amplification/polysomy in 5.5%.
- FGF2 expression correlated with basal-like TNBC; no survival impact from FGF family alterations.
Conclusions:
- Specific subsets of TNBC exhibit FGFR1 or FGFR2 gene amplification.
- FGFR1, FGFR2, or FGF2 protein overexpression occurs in TNBC subsets.
- Despite molecular alterations, no significant impact on patient survival was observed in this cohort.
