Expression of ICAM-1, MHC-1 and B7 surface molecules in canine primary appendicular osteosarcoma

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Fabiosa, Flor
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Osteosarcoma is the most common primary malignant bone tumor in dogs. The characteristic aggressive and highly metastatic behavior of this neoplasm indicates it has developed mechanisms to elude the immune surveillance system. The aim of the study was to determine whether canine primary appendicular osteosarcomas express ICAM-1, MHC-1 and B7 molecules which are critical in eliciting optimum immune response. Cell lines and tissue sections (frozen and paraffin-embedded, formalin-fixed tissues) of dogs with osteosarcoma were analyzed using fluorescence microscopy, flow cytometry and immunohistochemistry for expression of ICAM-1, MHC-1 and B7. All cell lines (n = 5) examined by fluorescence microscopy exhibited high ICAM-1 expression. Three out of five cell lines showed moderate expression of MHC-1 and low expression in two cell lines. B7 expression was measured using flow cytometry on 5 cell lines. Data showed that 4 out of 5 cell lines were positive for B7, positive cells ranged from 73.67 to 85.13 %. Frozen (n = 7) and paraffin-embedded, formalin-fixed (n = 17) tissue sections were examined using immunohistochemistry for expression of ICAM-1 and MHC-1. In frozen tumor sections, expression of ICAM-1 was high in tumors from 4 out of 7 (57.1%) dogs and 3 of 7 (43%) dog tumors expressed moderate staining. MHC-1 expression in tumors was observed in 4 of 7 (57. 1%) dogs with moderate staining while 3 of 7 (43%) exhibited low staining. In formalin-fixed, paraffin-embedded tumor sections, ICAM-1 showed high staining for tumors from 10 of 17 (59%) dogs and moderate staining in tumors from 7 of 17 (41.2%) dogs. MHC-1 showed low expression in tumors from 7 of 17 (41%) dogs and negative staining in tumors from 10 of 17 (59%) dogs. This study demonstrated high ICAM-1 expression in canine primary appendicular osteosarcomas, which could possibly explain its invasive nature and rapid metastasis. While B7 expression suggests, that these tumors are able to deliver costimulatory signal yet manage to escape from immune effector cells perhaps due to low MHC-1 expression. Results suggest that the tumor could use this strategy to interfere with antigen presentation by MHC-1 while possibly maintaining inhibitory signal to NIK cells.

Mon Jan 01 00:00:00 UTC 2001