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HER2 Amplification and Overexpression Is Not Present in Pediatric Osteosarcoma: A Tissue Microarray Study

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Pediatric and Developmental Pathology

Abstract

The HER2 gene, located on 17q, encodes a 185-kD transmembrane tyrosine kinase receptor. Amplification of this gene with overexpression of the gene product occurs in about 30% of cases of breast cancer and is considered to be a poor prognostic indicator for this tumor. Results for HER2 expression in osteosarcoma are controversial, with some studies reporting up to 61% of positive cases and others reporting only negative results. Further, expression of HER2 is reported to be a favorable prognostic indicator by some groups and unfavorable by others. The present study used tissue microarrays containing 34 samples of osteosarcoma from 18 patients to analyze HER2 expression by immunohistochemistry and gene copy number by chromogenic in situ hybridization. The microarray included 13 pretreatment biopsies, 11 posttreatment resection specimens, and 10 resected metastases and comprised 18 osteoblastic, 6 chondroblastic, 5 fibroblastic, and 5 mixed subtypes. HER2 protein expression was seen in 4 of 34 (12%) tumor samples that originated from 2 of 18 patients (11%). The staining pattern was consistently weak and focal, and immunohistochemical overexpression of the HER2 protein, defined as complete membrane positivity, was never observed. Further, the presence of HER2 gene amplification was not detected in any osteosarcoma by chromogenic in situ hybridization. Therefore, therapies based on antibodies directed against the HER2 protein are unlikely to have much value in the treatment of pediatric osteosarcomas. From a technical standpoint, this study also demonstrates the value of tissue microarrays in screening tumors at the protein and gene levels using conventional light microscopy.

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Acknowledgment

This research was supported by funding from the National Cancer Institute of Canada with funds from the Canadian Cancer Society.

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Authors and Affiliations

  1. Department of Pediatric Laboratory Medicine, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Gino R. Somers, Michael Ho, Maria Zielenska & Paul S. Thorner

  2. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine University of Toronto, Toronto, ON, M5S 1A1, Canada

    Gino R. Somers, Maria Zielenska, Jeremy A. Squire & Paul S. Thorner

  3. Department of Laboratory Medicine and Pathology, Princess Margaret Hospital, 610 University Avenue, Toronto, ON, M5G 2M9, Canada

    Jeremy A. Squire

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  1. Gino R. Somers
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  2. Michael Ho
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Correspondence to Gino R. Somers.

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Somers, G.R., Ho, M., Zielenska, M. et al. HER2 Amplification and Overexpression Is Not Present in Pediatric Osteosarcoma: A Tissue Microarray Study. Pediatr Dev Pathol 8, 525–532 (2005). https://doi.org/10.1007/s10024-005-0044-5

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  • DOI: https://doi.org/10.1007/s10024-005-0044-5

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