Altered intracellular localization of fibroblast growth factor receptor 3 in human breast cancer

Immunohistochemical staining of human breast tissues, using an antibody aga inst fibroblast growth factor receptor 3 [FGFR-3], showed differences in ce llular distribution. Both malignant and non-malignant epithelial cells cont ained FGFR-3 immunoreactivity, but myoepithelial cells and stroma were nega tive. The staining pattern in malignant epithelial cells was predominantly nuclear, whereas epithelial cells in normal breast tissue showed both cytop lasmic and nuclear elements. Reverse transcription-polymerase chain reactio n (RT-PCR) revealed two isoforms of FGFR-3 corresponding to the FGFR-3-IIIb variant and a previously described exon-deleted nuclear form of PGFR3, whi ch were present in both malignant and non-malignant epithelial cells. The h igher level of nuclear staining and loss of cytoplasmic staining seen in ma lignant epithelial cells did not correspond to an increase in expression of the exon-deleted form of FGFR-3, nor to any detectable activating point mu tations, Since receptor activation can result in its movement to a perinucl ear localization, an alternative explanation for the redistribution of FGFR 3-IIIb could be different degrees of activation by a ligand (FGF1 or FGF9), No FGF9 was detected by immunohistochemistry in breast tissues. FGF1, howe ver, is present in the majority of breast cancers and a different tissue di stribution of FGF1 was found in breast tissues, showing predominantly nucle ar, or a mis of nuclear and cytoplasmic FGFR-3, The difference in FGFR-3 st aining patterns may implicate this ligand-receptor pair in breast cancer. C opyright (C) 2001 John Wiley & Sons, Ltd.