Detection of FGFR3 by Immunohistochemistry in Multiple Myeloma Is Highly Predictive of t(4;14) by FISH and Is Associated with CD56 (NCAM1) Expression.

Recent studies have demonstrated that neural cell adhesion molecule CD56 (NCAM1) is involved in multiple adhesive interactions with several different classes of ligands on the cell surface and in the extracellular matrix. One of these ligands is fibroblast growth factor receptor (FGFR) family. While a direct interaction between CD56 (NCAM1) and FGFR3 is yet to be reported we have speculated that such interaction might exist in myeloma cells with aberrant FGFR3 expression. In order to test this hypothesis we have retrospectively examined the presence of t(4;14) in 127 multiple myeloma samples and its correlation with the presence of deletion 13 by FISH; FGFR3 and cyclin D1 expression by immunohistochemistry and CD56 expression as determined by flow cytometry. FISH detected t(4;14) in 32 (25.1%) of 127 MM patient specimens. 71.4% of t(4;14) positive samples were found to have deletion of chromosome 13, in contrast to only 34% in t(4;14) negative samples. Aberrant expression of FGFR3 was detected by immunohistochemistry in 14/21 or 66.7% of t(4;14) positive samples. No expression of FGFR3 was detected in 10 t(4;14) negative samples. As expected low Cyclin D1 expression by IHC was detected in t(4;14) positive samples (5/21 or 23.8%). More importantly all samples positive for FGFR3 by IHC were CD56 positive (14/14 or 100%) and in 21/22 (95.5%) of t(4;14) positive in contrast to 62% in t(4;14) samples. Further work is currently being conducted in order to examine the downstream signaling pathways that might be activated as a result of such possible interaction.