Background: Osteosarcoma is a rare primary malignant bone tumour, with poor prognosis, occurring mainly in adolescents. The bone invasion by a tumour cell affects the balance between bone resorption and formation, releasing factors initially trapped in the bone matrix and which in turn facilitate the tumour development. The main objectives of this work were to characterise the tumour bone microenvironment (or niche) of localised osteosarcoma or metastatic form of osteosarcoma by histopathological assessment correlated with the clinical annotations.
Methods: Fifty patients suffering from osteosarcoma were enrolled in this study (Nantes University Hospital, France). Analyses were carried out on the pre-operatory biopsies and two groups were defined: localised osteosarcoma (M-) and metastatic osteosarcoma with lung metastases (M+). The tumour niche was characterised by immunohistochemistry approaches: immune cells (macrophages with M1 and M2 polarised macrophages, lymphocytes, masts cells), vascularisation compartment (endothelial cells, smooth muscle cells, pericytes), cytokines/receptors (OPG and RANKL) and mitotic index.
Results: The present cohort included 22 non-metastatic osteosarcomas (M-), and 28 metastatic osteosarcomas (M+). A significant higher infiltration of M1-polarised macrophages was detectable in M- tumours compared with M+ tumours (INOS staining, p=0.001). In addition, M+ tumours exhibited a significantly higher vascular density (CD146 staining, p=0.01) compared with the M- group. OPG immunostaining was significant increased in M- osteosarcomas compared to M+ tumours (p=0.02). In multivariate analyses, INOS and OPG were predictive factors of metastasis (p=0.02 and p=0.03, respectively).
Conclusion: It is an original study, with clinical annotations, comparing tumour bone microenvironment of osteosarcomas with or without metastasis. M1-polarised macrophages and OPG, have predictive factor of the metastastic process. A difference between metastatic or primary osteosarcoma microenvironment was demonstrated leading to propose predictive factors of the metastatic process.
Disclosure: The authors declared no competing interests. This work was supported by the Ligue Nationale Contre le Cancer (Equipe LIGUE 2012) and by INSERM.