Fibroblast growth factor receptor 3 (FGFR3) expression in malignant lymphomas

Fibroblast growth factor receptor 3 (FGFR3) protein is aberrantly expressed in approximately 15% of cases of plasma cell myeloma as a result of t(4;14)(p16.3;q32), and FGFR3 expression in myeloma is associated with an adverse prognosis. Novel, recently developed therapeutic agents that target the FGFR3 pathway are currently in clinical trials for myeloma. Although extensively studied in plasma cell neoplasms, there is little information in the literature regarding FGFR3 expression in malignant lymphomas, and it is unclear whether lymphoma patients may also benefit from anti-FGFR3 therapy. We, therefore, examined the expression of FGFR3 by immunohistochemistry in 70 cases of malignant lymphoma using tissue microarrays and whole paraffin sections. Of 22 cases of plasma cell myeloma analyzed as controls, FGFR3 positivity was seen in 3/5 t(4;14) positive cases (60%) and in none of 17 t(4;14) negative cases (P=0.006). Weak-to-moderate cytoplasmic FGFR3 staining was seen in 6/43 (12%) B-cell non-Hodgkin lymphomas and 2/17 (12%) T-cell lymphomas, with staining observed at low incidence in many histologic types. Cytoplasmic staining was also seen infrequently in classic Hodgkin lymphoma (1/10, 10%). Membrane staining was not observed in any case of malignant lymphoma. These results indicate that aberrant FGFR3 staining may be seen infrequently in many forms of malignant lymphoma, although dysregulation of this pathway does not seem to contribute to lymphomagenesis in the majority of cases. Moreover, these findings suggest at least most patients with malignant lymphomas are unlikely to benefit from novel agents targeting the FGFR3 pathway.