Connective Tissue Oncology Society

2001 CTOS Annual Meeting Posters— Pathology

EXPRESSION OF HER2/NEU (HER2) AND EGFR IN OSTEOSARCOMA (OS)
James C Wittig¹, Lorna Cruz³, Felasfa Wodajo¹, WM Chu², Kristen L Kellar-Graney¹, Nita Seibel⁴, Dhruv Kumar³, Martin M Malawer¹, Dennis A Priebat²
¹Dept of Orthopedic Oncology Washington Cancer Institute Washington Hospital Center, ²Deptartment of Hematology/Oncology Washington Cancer Institute Washington Hospital Center, ³Department of Pathology Washington Hospital Center, ⁴Children's National Medical Center Department of Pediatric Hematology/Oncology

OBJECTIVE: Overexpression of protooncogenes and cellular growth factor receptors have been implicated in the development of osteosarcomas. HER2 (human epidermal growth factor receptor 2) is a 185-Kd transmembrane glycoprotein receptor that is the product of the c-erbB-2 protooncogene. It is structurally homologous to EGFR (epidermal growth factor receptor). Recent studies have reported that 42%-45% of OS overexpress HER2 and that overexpression of HER2 in OS correlates with a worse event-free survival, and a poor histologic response to induction chemotherapy. This has stimulated interest in investigating the use of anti-HER2 monoclonal antibodies in treatment protocols as part of initial or salvage chemotherapy regimens for poor prognosis patients. Expression of EGFR in OS has not been thoroughly investigated although its overexpression by other tumor types has been correlated with a poor prognosis. The purpose of this study was to examine the expression of HER2 and EGFR in OS and to determine the relationship between overexpression and survival, response to induction chemotherapy, local and systemic recurrence, and various other potential prognostic factors.

METHODS: Archival paraffin embedded tissue from 32 patients with the diagnosis of high-grade OS were stained for HER2 (Hercep Test- DAKO Corp) and EGFR (Mouse Anti-EGFR, ZYMED LABS) via standard immunohistochemical techniques. Cellular membrane staining was graded 0 to 3+ according to intensity. The receptors were considered to be overexpressed if grade 2 or 3 staining was present.

RESULTS: HER2 was not expressed in any specimen. (All specimens demonstrated grade 0 staining for HER2.) EGFR was overexpressed in five (16%) specimens. Overexpression of EGFR did not correlate with prognosis or with any significant prognostic variables.

CONCLUSION: HER2 and EGFR do not demonstrate significant nor consistent overexpression by OS cells. They are unlikely to represent important prognostic variables. Therapy with anti-HER2 antibody or IMC-C225 (anti-EGFR ab) may not be beneficial. Further investigation is required.