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Sarcoma Research Series

Epidermal Growth Factor Receptor Expression and Mutational Analysis in Synovial Sarcomas and Malignant Peripheral Nerve Sheath Tumors

^aDepartment of Medicine, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA; ^bDepartment of Pathology, ^cDepartment of Orthopedic Surgery, ^dDepartment of Internal Medicine, Division of General Medicine, and ^eDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, USA

Key Words. Synovial sarcoma • Malignant peripheral nerve sheath tumor • Immunohistochemistry • EGFR • Mutation analysis

Correspondence: Laurence H. Baker, D.O., Department of Internal Medicine, Division of Hematology/Oncology, 24 Frank Lloyd Wright Drive, A3400, PO Box 483, Ann Arbor, Michigan 48106, USA. Telephone: 734-998-7130; Fax: 734-998-7118; e-mail: bakerl{at}umich.edu

Disclosure: L.H.B. is an advisory board member of Ascenta Therapeutics, Inc., The Hope Foundation, NCCN Guidelines Committee, and SARC (Sarcoma Alliance for Research through Collaboration), for which he receives no compensation. No other potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.

Background. Synovial sarcomas (SnSrcs) and malignant peripheral nerve sheath tumors (MPNSTs) are rare mesenchymal tumors of adolescence and young adulthood. Previous work from our laboratory has demonstrated that SnSrcs express epidermal growth factor receptor (EGFR) and human EGFR (HER)-2/neu. The present study extends that work to examine the expression of EGFR in MPNSTs and the characterization of potential targets of the EGFR tyrosine kinase domain.

Methods. Tissue microarrays containing 48 cases of SnSrc and 32 cases of MPNST were stained for EGFR, EGFRvIII, and activated EGFR (pY1068-EGFR). Tumor DNA was extracted from fresh and formalin-fixed, paraffin-embedded tissue blocks and sequenced for exons 17–21 of EGFR and exon 2 of K-ras and b-raf.

Results. Immunohistochemistry (IHC) demonstrated that EGFR is expressed in a majority of SnSrcs and MPNSTs (71% and 62.5%, respectively). EGFRvIII immunoreactivity was negative. IHC was weakly immunopositive for activated EGFR (18.7% and 3.1%, respectively). Sequence analysis of the EGFR genomic DNA did not demonstrate mutations in exons 17–21. No K-ras or b-raf mutations were observed in either tumor type.

Conclusions. Expression of EGFR in SnSrcs and MPNSTs with an intact EGFR/mitogen-activated protein kinase pathway has been hypothesized to contribute to the malignant potential of these tumors. Our study reveals the absence of known activating mutations in EGFR, which suggests that trials of small-molecule inhibitors would be of little clinical benefit. A clinical study of treatment with cetuximab is ongoing and may help elucidate whether blockade of EGFR with antibodies is likely to be more active.

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