FGFR4 overexpression and hotspot mutations in metastatic ER+ breast cancer are enriched in the lobular subtype

FGFR4 expression is elevated in cell lines and patient samples treated with endocrine therapy. a Top, FGFR4 RNA expression fold-change in long-term endocrine-resistant cell line models of ER+ breast cancer, relative to parental cell lines with short-term estrogen deprivation. From left to right, tamoxifen-resistant cells from {"type":"entrez-geo","attrs":{"text":"GSE12708","term_id":"12708"}}GSE12708, long-term estrogen deprived (LTED) cells from {"type":"entrez-geo","attrs":{"text":"GSE75971","term_id":"75971"}}GSE75971, LTED cells from {"type":"entrez-geo","attrs":{"text":"GSE116744","term_id":"116744"}}GSE116744. *p？<？0.05 for differential expression versus parental, corrected for multiple comparisons with Benjamini–Hochberg. Bottom, qRT-PCR and immunoblot comparison of FGFR4 expression in MM134 and SUM44 LTED cells, relative to parental cells grown in FBS. Error bars represent？±？SD for three biological replicates. Red bars represent ILC and blue bars represent IDC. b Top, FGFR4 expression gain in 29 ER+ paired tumors. Bottom, FGFR4 expression gain in the tumors separated by site of metastasis (met). Red lines represent primary tumor histology of ILC, blue lines represent IDC, and green lines represent mixed IDC/ILC tumors. Two-sided paired Wilcoxon rank tests were used to calculate p values for FGFR4 gain. c IHC staining of an orphan bone metastasis (left, no primary antibody. right, FGFR4 (MABD120, 1:250 dilution)). d IHC staining of FGFR4 (MABD120, 1:250 dilution) in a paired primary breast tumor and endocrine-treated local recurrence. Scale bars represent 100？μm. See Supplementary Material for additional antibody validatio