Epithelioid sarcoma expresses epidermal growth factor receptor but gene amplification and kinase domain mutations are rare

Michael Cascio, Richard J. O'Donnell, Andrew E. Horvai

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 shows morphologic and immunophenotypic evidence of epithelial differentiation. Current therapeutic strategies include surgical resection, amputation, radiation or chemotherapy, although the overall prognosis remains poor. The 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 sarcoma types, but expression, amplification and mutations have not been studied in epithelioid sarcoma. We evaluated 15 cases of epithelioid sarcoma from 14 patients for EGFR expression using immunohistochemistry, EGFR copy number aberration using fluorescence in situ hybridization and screened for mutations in the tyrosine kinase domain of the EGFR gene using direct sequencing. In all, 14 of the 15 epithelioid sarcomas (93%) showed expression of EGFR by immunohistochemistry. A majority of the cases (n11, 73%) showed strong (2 to 3) and homogeneous (75% of cells) membrane staining. No amplification or polysomy of the EGFR gene or mutations of the tyrosine kinase domain of EGFR (exons 18-21) were detected. These results imply that although EGFR is expressed in most epithelioid sarcomas regardless of subtype, gene amplification and activating mutations in the tyrosine kinase domain appear to be rare or absent. Thus, the benefit of targeted therapy against EGFR in patients with epithelioid sarcoma remains to be determined.

Original languageEnglish (US)
Pages (from-to)574-580
Number of pages7
JournalModern Pathology
Volume23
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

Fingerprint

erbB-1 Genes
Gene Amplification
Epidermal Growth Factor Receptor
Sarcoma
Mutation
Protein-Tyrosine Kinases
Immunohistochemistry
Soft Tissue Neoplasms
Carcinoma
Fibroma
Fluorescence In Situ Hybridization
Amputation
Exons
Therapeutics
Cell Membrane
Radiation
Staining and Labeling
Drug Therapy

Keywords

  • Epidermal growth factor
  • Epithelioid sarcoma
  • Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Epithelioid sarcoma expresses epidermal growth factor receptor but gene amplification and kinase domain mutations are rare. / Cascio, Michael; O'Donnell, Richard J.; Horvai, Andrew E.

In: Modern Pathology, Vol. 23, No. 4, 04.2010, p. 574-580.

Research output: Contribution to journalArticle

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abstract = "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 shows morphologic and immunophenotypic evidence of epithelial differentiation. Current therapeutic strategies include surgical resection, amputation, radiation or chemotherapy, although the overall prognosis remains poor. The 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 sarcoma types, but expression, amplification and mutations have not been studied in epithelioid sarcoma. We evaluated 15 cases of epithelioid sarcoma from 14 patients for EGFR expression using immunohistochemistry, EGFR copy number aberration using fluorescence in situ hybridization and screened for mutations in the tyrosine kinase domain of the EGFR gene using direct sequencing. In all, 14 of the 15 epithelioid sarcomas (93{\%}) showed expression of EGFR by immunohistochemistry. A majority of the cases (n11, 73{\%}) showed strong (2 to 3) and homogeneous (75{\%} of cells) membrane staining. No amplification or polysomy of the EGFR gene or mutations of the tyrosine kinase domain of EGFR (exons 18-21) were detected. These results imply that although EGFR is expressed in most epithelioid sarcomas regardless of subtype, gene amplification and activating mutations in the tyrosine kinase domain appear to be rare or absent. Thus, the benefit of targeted therapy against EGFR in patients with epithelioid sarcoma remains to be determined.",
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