Clinicopathologic Analysis of HER-2/neu Immunoexpression among Various Histologic Subtypes and Grades of Osteosarcoma

• Published in: Modern pathology 2001-12, Vol.14 (12), p.1277-1283
• Main Authors: Kilpatrick, Scott E, Geisinger, Kim R, King, Tonya S, Sciarrotta, Janiece, Ward, William G, Gold, Stuart H, Bos, Gary D
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies; Antibodies, Neoplasm - analysis; Antigens; Automation; Bone cancer; Bone Neoplasms - classification; Bone Neoplasms - metabolism; Bone Neoplasms - mortality; Bone Neoplasms - pathology; Breast cancer; Breast Neoplasms - chemistry; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Intraductal, Noninfiltrating - chemistry; Carcinoma, Intraductal, Noninfiltrating - metabolism; Carcinoma, Intraductal, Noninfiltrating - secondary; Chemotherapy; Child; Female; Fluorescent Antibody Technique, Indirect; Grade; HER-2/neu; Humans; Immunoenzyme Techniques; Immunohistochemistry; Laboratory Medicine; Male; Medicine & Public Health; Metastasis; Middle Aged; original-article; Orthopedics; Osteosarcoma; Osteosarcoma - classification; Osteosarcoma - metabolism; Osteosarcoma - mortality; Osteosarcoma - pathology; Pathology; Reagents; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - biosynthesis; Receptor, ErbB-2 - immunology; Subtypes; Survival Rate
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.3880474

Overexpression of the HER-2/neu oncogene appears to have prognostic significance in breast cancer. Recently, some have reported a relationship between increased immunohistochemical expression in osteosarcoma and poor clinical outcome. Despite limited data, a pilot trial of Herceptin, which targets the oncogene product, has been initiated for the therapy of some metastatic osteosarcomas (CCG-P9852). Archival formalin-fixed, paraffin-embedded tissue obtained from 41 patients diagnosed with osteosarcoma was examined immunohistochemically by 2 antibodies against the HER-2/neu oncogene product: CB-11 (monoclonal, 1/100) and Oncor (polyclonal, 1/200). All but one tumor (case of recurrent dedifferentiated parosteal osteosarcoma) represented primary tumor samples; when applicable, only prechemotherapy biopsies were analyzed. The study sample included the full spectrum of histologic subtypes and grades of osteosarcoma (25 conventional high grade; 3 telangiectatic; 1 small cell; 6 parosteal; 1 periosteal; and 5 low-grade intramedullary). A case of metastatic breast cancer with known overexpression of the HER-2/neu oncogene served as the positive control. Complete membranous positivity, considered prognostically significant in breast cancer, was not seen in any of our osteosarcoma cases. At least focal cytoplasmic positivity was documented in 40 (98%) tumors using the CB11 antibody and in 34 (83%) using the Oncor antibody. The intensity of the cytoplasmic staining (0, 1–3+) did not correlate with histologic subtype/grade, response to chemotherapy (