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Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 317 - 317
1 Nov 2002
Merimsky O Issakov J Dadia S Kollender Y Schwartz I Bickels J Flusser G Inbar M Meller I
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Background: The c-ebB-2 gene and its products (also designated HER-2 and c-neu) encode for a 185-kd transmembrane glycoprotein with intracellular tyrosine kinase activity. C-erbB-2 belongs to the epidermal growth factor receptor family, of which there are four known members, and has molecular homology to the epidermal growth factor receptor. It seems that this family is critical in control of growth, differentiation, and mobility of many normal and transformed epithelial cell types.

Materials and Methods: We have looked for over expression of c-erbB-2 gene product in 230 cases of soft tissue sarcoma, in order to establish a possible new prognostic marker, and a potentially new treatment option.

Results: In all the cases, irrespective of the sarcoma histological type, the immunostaining for erbB-2 was negative.

Conclusions: Applications of erbB-2 for prognostication as well as the option of receptor targeting by trastuzumab monoclonal antibodies were aborted.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 317 - 317
1 Nov 2002
Merimsky O Issakov J Kollender Y Inbar M Bickels J Meller I
Full Access

Background: We have recently observed that many of our sarcoma patients presented also with thyroid disorders. Literature data are almost unavailable on this topic.

Materials and Methods: Retrospective analysis of files of patients with sarcoma and clinically overt thyroid disorders.

Results: Out of 375 patients with soft tissue sarcomas (STS) and 235 with bone sarcoma (BS) including small blue round cell tumors (SBRC), 28 patients (4.6%) had an associated significant thyroid disorder. The types of sarcoma were mainly liposarcoma followed by malignant fibrous histiocytoma, leiomyosarcoma and bone sarcoma. The primary sites were mainly limb and trunk. The interval between the diagnosis of the thyroid disorder and the sarcoma varied between {−14} years (thyroid first) and {+16.5} years (thyroid later) with a median of {−0.2} years. Thyroid disorders included goiter, thyroiditis and carcinoma.

Conclusions: There are basic-science and clinical evidences to a possible common pathway that leads to the association between overt thyroid disorders and sarcomas of bone or soft tissues. Oncogene erbA activity is related to thyroid receptors to T3 and to development of sarcoma. Cross talk of the sarcoma oncogene and the erbA might contribute to the development of sarcoma. The thyroid hormone receptor and the highly related viral oncoprotein v-erbA are found exclusively in the nucleus as stable constituents of chromatin. It has been shown that v-erbA can block the spontaneous differentiation in erythroid cells transformed by various retroviral oncogenes. V-erbA can alter the spectrum of neoplasia induced by the v-src oncogene, which causes predominantly sarcomas and erythroblastosis in chicks. The erbA can cooperate with other oncogenes such as v-erbB or with v-fms, v-ras, and c-kit. Cooperation with v-myc may play a role in the development of rhabdomyosarcoma especially in thyroid hormone deficiency state. The possible clinical implications are the need to screen patients with sarcoma to thyroid disorders, and patients with thyroid disorders for malignant diseases.