Growth factor receptor expression in orbital lymphangioma: Possible therapeutic implications

OBJECTIVE: To examine the expression of molecules targeted by imatinib mesylate (STI571;Gleevec) and epidermal growth factor receptor (EGFR) inhibitors in orbital lymphangiomas. DESIGN: Retrospective observational case series. PARTICIPANTS: Six patients with orbital lymphangioma treated at four institutions between March 2000 and December 2002. METHODS: Tissue specimens and medical records from six patients were collected. Immunohistochemical analysis was performed using antibodies against c-kit and platelet-derived growth factor receptor (PDGFR) alpha and beta and EGFR tyrosine kinase. MAIN OUTCOME MEASURES: Expression of c-kit, PDGFR alpha and beta, as well as EGFR receptors in orbital lymphangioma. RESULTS: PDGFR alpha and beta receptors were expressed on the endothelial and smooth muscle cells of the vascular channels of the lymphangioma in all six patients. Five of six orbital specimens demonstrated expression of EGFR on the smooth muscle cells of the vascular channels. C-kit was expressed by mast cells. CONCLUSIONS: PDGFR alpha expression by the endothelial cells lining orbital lymphangiomas suggests a possible role for PDGF in the angiogenic activity of this tumor. Clinical trials should be designed to investigate the efficacy of specific inhibitors of PDGFR, such as imatinib mesylate, as single agents or in combination with EGFR inhibitors for treatment of refractory orbital lymphangioma.