Epithelioid Sarcoma Expresses Epidermal Growth Factor Receptor but Gene Amplification and Kinase Domain Mutations Are Rare
MJ Cascio, RJ O'Donnell, AE Horvai. UCSF, San Francisco, CA
Background: Epithelioid sarcoma is a rare, malignant, soft tissue neoplasm that can be classified into proximal, distal and fibroma-like subtypes. Regardless of subtype, epithelioid sarcoma often demonstrates morphologic and immunophenotypic evidence of epithelial differentiation. Current therapeutic strategies include radical resection, amputation, radiation or chemotherapy although prognosis is poor. Epidermal growth factor receptor (EGFR) is a novel therapeutic target in carcinomas. In some carcinomas, EGFR kinase domain mutations or gene amplification may correlate with response to specific inhibitors. EGFR expression has been reported in some sarcomas, but expression, amplification and kinase mutations have not been studied in epithelioid sarcoma.
Design: We evaluated 13 cases of epithelioid sarcoma (6 distal, 6 proximal and 1 fibroma-like) for expression of EGFR by immunohistochemistry using formalin-fixed, paraffin-embedded tissue. Each sample was stained and scored according to established methods (EGFR pharmDx, Dako, Carpinteria, CA) and the fraction of cells staining was also recorded. EGFR gene amplification and polysomy were evaluated using fluorescence in situ hybridization (FISH) performed on paraffin-embedded tissue. All cases were tested for kinase domain mutations (exons 18-21) by PCR and direct sequencing.
Results: Twelve of thirteen epithelioid sarcomas (92%) showed expression of EGFR by immunohistochemistry. Most cases (n=8, 62%) showed strong (3+) and homogeneous (>75% of cells) membrane staining. FISH demonstrated no amplification of the EGFR gene (EGFR:centromere ratios ranged from 0.93 to 1.03). Forward and reverse nucleotide sequencing of the tyrosine kinase domain of the EGFR gene (exons 18-21) failed to reveal point mutations, insertions, or deletions in any case.
Conclusions: EGFR is expressed in most epithelioid sarcoma regardless of subtype. However, EGFR gene amplification and activating mutations in the tyrosine kinase domain appear to be rare or absent in these tumors. Thus, the benefit of targeted therapy against EGFR in patients with epithelioid sarcoma remains to be determined.
Category: Bone & Soft Tissue
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 14, Monday Morning