Posters— Diagnostic Imaging/Pathology

HER2/NEU EXPRESSION IN OSTEOSARCOMAS AND OTHER BONY SARCOMAS

Thomas D, Giordano T, Sanders D, Arrowsmith P, Baker L. (University of Michigan Comprehensive Cancer Center, Ann Arbor, M1 48109)

Osteosarcoma and skeletal Ewing’s sarcoma are the most common primary bone tumors in the pediatric age group. Both are aggressive malignancies with a tendency for early and rapid pulmonary metastasis. Advances in surgical oncology and adjuvant pre-operative chemotherapy have increased the overall 5-year survival to approximately 70%. However, although this represents the majority of patients, patients who relapse rarely respond to salvage therapy. Clearly there is a need for alternate adjuvant chemotherapy for these patients. Recently, there have been conflicting reports about the expression of c-erb B2 proto-oncogene product in osteosarcomas and Ewing’s sarcoma. The c-erb B2 proto-oncogene encodes the human epidermal growth factor receptor 2 (Her2/Neu); a membrane bound tyrosine kinase, which when over expressed in rodent fibroblasts causes malignant transformation. Several groups of authors have claimed that a high percentage of osteosarcomas express Her2/Neu and that either this portends a poor prognosis or was associated with a decreased risk of relapse. Archival cases of osteosarcomas (n=38., including preand posttreatment samples, age range 6-27 years) and Ewing’s sarcoma (n=11, age range 16 months-22 years) were retrieved and the diagnosis confirmed. Specimens were assessed for Her2/Neu oncogene expression by standard immunohistochernical techniques. Several cases demonstrated cytoplasmic staining, but none showed the membranous staining characteristic of over-expression by breast carcinomas. To validate the negative immunostains, reverse transcriptase polymerase chain reaction of RNA extracted from archival material also failed t-Odemonstrate the presence of mRNA for c-ErbB2, even though appropriate internal controls were positive. Our results demonstrate that ErbB2 expression in either osteosarcomas and Ewing’s sarcoma is not common and thus not likely to be an important prognostic factor and further that therapy with recombinant humanized anti-HER2 monoclonal antibodies may not be appropriate therapy for these patients.

Kindly supported by the Walther Cancer Institute