Immunohistochemical detection of c-fos and c-jun expression in osseous and cartilaginous tumours of the skeleton

Abstract

The products of c-fos and c-jun proto-oncogenes form the heterodimeric complex AP-1 (activator protein 1), which play an important part in the control of bone cell proliferation and differentiation and in the development of bone tumours. We examined the expression of c-fos and c-jun in a series of 52 primary skeletal neoplasms, using an immunohistochemical method on formalin-fixed, paraffin-embedded sections. The expression of c-fos and c-jun was restricted to bone-forming lesions, while cartilaginous tumours were devoid of immunoreactivity. In benign osteoblastic lesions moderate c-fos and c-jun expression was found in 2 cases (18.1%). The highest levels of c-fos and c-jun expression were detected in high-grade central osteosarcomas (7 of 15 cases with moderate/diffuse expression) while 1 telangiectatic osteosarcoma, 2 low-grade central osteosarcomas, 1 low-grade periosteal osteosarcoma and 7 low-grade parosteal osteosarcomas were either negative or had low expression. The high-grade component of a dedifferentiated parosteal osteosarcoma showed diffuse immunoreactivity for both oncoproteins. Comparison of c-fos and c-jun expression by histological grade showed that high-grade osteosarcomas had a significantly higher expression of both oncoproteins than did low-grade osteosarcomas (P = 0.01, Fisher's exact test). Thus, c-fos and c-jun overexpression may be implicated in the development of high-grade osteosarcomas, but they appear to have little or no relevance for the development of low-grade osteosarcomas and cartilaginous skeletal neoplasms.

c-Jun knockdown sensitizes osteosarcoma to doxorubicin

“…1), akin to findings in an earlier study (4). Areas within the tumor that had a less differentiated pattern, that is a more aggressive growth pattern, were more intensely stained than those with a greater differentiation status.…”

“…These findings have important clinical implications because c-Jun levels are elevated with increasing grade of osteosarcoma (4,5). The efficacy of the DNAzyme was heightened when combined with doxorubicin, a frontline chemotherapeutic for osteosarcoma.…”

“…One such molecule is c-Jun, a member of the basic regionleucine zipper (bZIP) protein family that homodimerizes and heterodimerizes with other bZIP proteins to form the transcription factor activating protein-1 (3). c-Jun has been found to be increased in higher-grade osteosarcoma (4,5). Because no report exists of c-Jun mRNA silencing as a potential therapy modality for osteosarcoma, we embarked on this investigation.…”

MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone

“…18,[35][36][37][38][39][40] Okada et al 41 studied eight cases of low-grade central osteosarcomas retrospectively and showed that proliferative cell activity evaluated by AgNOR and MIB-1 immunohistochemical staining was significantly higher in cases of low-grade central osteosarcoma than in fibrous dysplasia and might be helpful in differentiating low-grade central osteosarcoma from fibrous dysplasia. Pollandt et al 42 showed that Gsalpha gene mutations were a constant finding in cases of monostotic fibrous dysplasia.…”

“…These tumors seem to share similarities in changes in cytogenetics and molecular genetics involving ring or giant marker chromosomes, which contain amplification of the 12q13-15 region, including murine doubleminute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4). [16][17][18][19][20][21] The purpose of this study was to determine the value of MDM2 and CDK4 immunostaining for the differential diagnosis of low-grade osteosarcomas and benign fibrous or fibro-osseous lesions. We then investigated the immunohistochemical status of 72 low-grade osteosarcomas and 107 fibrous or fibro-osseous lesions of the bone or paraosseous soft tissue.…”