Background: Dominant negative inhibition of nuclear factor kB (NFkB) signalling activity in a human osteosarcoma cell line (Saos2) results in malignant reversion and the induction of the osteoblast differentiating transcription factor, Runx2/ Cbfa1. This observation suggests that there is an inverse relation between a transcription factor associated with malignant progression and chemoresistance (NFkB) and an osteoblast differentiating transcription factor (Runx2/Cbfa1). Aims: To assess and correlate Runx2/Cbfa1 and NFkB (p65) immunoreactivity in human osteosarcoma. Methods: Runx2/Cbfa1 and NFkB (p65) immunoreactivity was assessed on 11 paraffin wax embedded archival specimens of human primary osteosarcoma by standard immunohistochemical methods and scored on a scale of 0-3. A Pearson correlation analysis between Runx2/Cbfa1 and NFkB (p65) scores was established. Results: Runx2/Cbfa1 was expressed constitutively in all pathology specimens of human osteosarcoma. Of note, a chondroblastic osteosarcoma showed the highest Runx2/ Cbfa1 immunoreactivity. A Pearson correlation did not support an inverse correlation between Runx2/Cbfa1 and NFkB (p65) scores (r = 0.57) in human osteosarcoma. Conclusion: Runx2/Cbfa1 immunoreactivity does not inversely correlate with NFkB immunoreactivity, and thus cannot serve as an indirect measure of NFkB activity or an independent predictive or prognostic indicator. O steosarcoma is the most common primary bone malignancy, with a propensity for pulmonary metastasis and a predilection for paediatric and geriatric age groups. The cornerstone of current clinical management involves high dose neoadjuvant chemotherapy, to which 40-60% of cases are non-responsive. Thus, prognosticating, stratifying, and individualising treatment is crucial for optimal and cost effective management. 1 ''Although the NFkB activation status of a tumour has predictive and prognostic value, it cannot be measured by routine laboratory investigations'' Histopathologically, osteosarcomas are characterised by atypical cells (osteoblasts, mesenchymal cells, fibroblasts, and chondrocytes) enmeshed in a disorganised bony matrix (immature osteoid). We recently showed that dominant negative inhibition of the promalignant transcription factor, nuclear factor kB (NFkB), in a human osteosarcoma cell line (Saos2) results in malignant reversion and the induction of the osteoblast differentiating transcription factor, Runx2/ Cbfa1.2 3 This finding was interesting for two reasons:N It validated the concept that cellular differentiation and transformation are mutually exclusive processes.N It suggested an inverse relation between a transcription factor associated with malignant progression 4 and chemoresistance (NFkB) 5 and an osteoblast differentiating transcription factor (Runx2/Cbfa1).Although the NFkB activation status of a tumour has predictive and prognostic value, it cannot be measured by routine laboratory investigations. Our present study was designed to assess whether Runx2/Cbfa1 expression could serve as an indirect me...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.