EGFR Expression, Amplification and Kinase Domain Mutations Are Rare in Epithelioid Vascular Neoplasms
R Gill, RJ O'Donnell, AE Horvai. UCSF, San Francisco, CA
Background: Epithelioid vascular neoplasms represent a spectrum of tumors ranging from benign epithelioid hemangioma, intermediate grade epithelioid hemangioendothelioma to malignant epithelioid angiosarcoma. Patients diagnosed with the latter two uncommon tumors have few therapeutic options and might benefit from targeted inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase activity. Treatment with kinase inhibitors has been well established for carcinomas, in which the presence of kinase domain mutations or EGFR gene amplification may correlate with clinical response to specific inhibitors.
Design: We evaluated 17 epithelioid hemangioendotheliomas (EHE) and 10 epithelioid angiosarcomas (EA) for EGFR expression by immunohistochemistry, on formalin-fixed paraffin embedded tissue. Each sample was scored (1-4+) and characterized as positive or negative. Positive cases were further analyzed by dual color fluorescence in-situ hybridization (FISH) for EGFR amplification or polysomy. Finally, positive cases were tested for kinase domain mutations in exons 18-21 by PCR and direct sequencing.
Results: Three of the EHE cases (18%) and one EA case (10%) had detectable membrane EGFR by immunohistochemistry with 1+ to 3+ intensity and 25% to 100% of tumor cells staining. However, none of these demonstrated EGFR gene amplification by FISH (EGFR to centromere ratios ranged from 0.85 to 1.0). One EHE case demonstrated a single base change in exon 19. This corresponded to a P753R missense mutation. A second EHE case demonstrated a silent base change in exon 20 (at Gln787). None of the EA cases demonstrated mutations in exons 18-21 of EGFR.
Conclusions: The expression of EGFR is rare in EHE and EA. A subset of these epithelioid vascular tumors demonstrate immunohistochemically detectible EGFR but the absence of gene amplification and rarity of kinase domain mutations suggests that few patients, if any, may benefit from targeted therapy.
Category: Bone & Soft Tissue
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 5, Tuesday Morning