[Show abstract][Hide abstract] ABSTRACT: Single Nucleotide Polymorphisms (SNPs) in intron 2 of the Fibroblast Growth Factor Receptor Type 2 (FGFR2) gene, including rs2981582, contribute to multifactorial breast cancer susceptibility. The high risk polymorphism haplotype in the FGFR2 gene has been associated with increased mRNA transcription and altered transcription factor binding but the effect on FGFR2 protein expression is unknown. 40 breast tumours were identified from individuals with known rs2981582 genotype. Tumour sections were stained for FGFR2 protein expression, and scored for nuclear and cytoplasmic staining in tumour and surrounding normal tissue.
FGFR2 immunohistochemistry demonstrated variable nuclear staining in normal tissue and tumour tissue, as well as consistent cytoplasmic staining. We did not find an association between nuclear staining for FGFR2 and genotype, and there was no association between FGFR2 staining and estrogen or progestogen receptor status. There was an association between presence of nuclear staining for FGFR2 in normal tissue and presence of nuclear staining in the adjacent tumour (Fishers exact test, p = 0.002).
Variable nuclear staining for FGFR2 in breast cancer, but an absence of correlation with rs2981582 genotype suggests that the mechanism of action of polymorphisms at the FGFR2 locus may be more complex than a direct effect on mRNA expression levels in the final cancer. The effect may relate to FGFR2 function or localisation during breast development or tumourigenesis. Nuclear localisation of FGFR2 suggests an important additional role for this protein in breast development and breast cancer, in addition to its function as a classical cell surface receptor.