Craniofacial Osteosarcoma—Pilot Study on the Expression of Osteobiologic Characteristics and Hypothesis on Metastasis

Abstract

Background: Craniofacial osteosarcomas (COS) and extracranial osteosarcomas (EOS) show distinct clinical differences. COS show a remarkably lower incidence of metastases and a better survival. However, in contrast to EOS, they show a poor response to neoadjuvant chemotherapy. Tumor-associated macrophages and their polarization as well as developmental biological signaling pathways are possible candidates for explaining the clinical differences between COS and EOS. The aim of the study was to analyze differential expression of macrophage markers and important regulators of these pathways. Methods: Twenty osteosarcoma cases (10 COS and 10 EOS) were immunohistochemically stained to assess CD68, CD11c, CD163, MRC1, Gli1, and Gli2 expression. Statistical differences between COS and EOS were tested using the Mann-Whitney U test. Additionally, the paper describes an example of multidisciplinary treatment of a patient suffering from COS and discusses the surgical challenges in treatment and rehabilitation of COS. Results: COS showed a significantly (p < 0.05) increased infiltration of CD11c-positive M1 macrophages and a shift toward M1 polarization compared to EOS. Additionally, COS revealed a significantly (p < 0.05) lower Gli1 expression than EOS. Conclusion: The reduced Gli1 expression in COS can be interpreted as reduced activation of the Hedgehog (Hh) signaling pathway. The increased M1 polarization and reduced Hh activation in COS could explain the low incidence of metastases in these osteosarcomas.

Infiltration of LPAR5+ macrophages in osteosarcoma tumor microenvironment predicts better outcomes

“…It was reported that M1 macrophages promoted inflammatory responses, were capable of antigen presentation and the activation of T cells, and therefore have anti-tumor and anti-metastatic effects (81,82). Manuel Weber et al compared the difference in macrophage infiltration between craniofacial osteosarcoma (COS) and extracranial osteosarcoma (EOS) and found that M1 macrophages were more infiltrated in COS, which could explain the low probability of metastasis in COS (83). M2 macrophages were reported to have immunomodulatory effects and were associated with wound healing, immunosuppression, tumor progression and metastasis (84)(85)(86).…”

“…Manuel Weber et al. compared the difference in macrophage infiltration between craniofacial osteosarcoma (COS) and extracranial osteosarcoma (EOS) and found that M1 macrophages were more infiltrated in COS, which could explain the low probability of metastasis in COS ( 83 ). M2 macrophages were reported to have immunomodulatory effects and were associated with wound healing, immunosuppression, tumor progression and metastasis ( 84 – 86 ).…”

The Special Developmental Biology of Craniofacial Tissues Enables the Understanding of Oral and Maxillofacial Physiology and Diseases

“…The different clinical behavior of craniofacial versus extracranial osteosarcoma may be due to the different developmental biology of craniofacial and extracranial bone. A different activation of the Hedgehog signaling pathway and also possible immunologic differences between craniofacial and extracranial osteosarcomas have already been shown [ 19 ].…”

Efficacy of Recombinant Human Endostatin plus Neoadjuvant Chemotherapy for Osteosarcoma and Its Influence on Serum VEGF and MMP-9 Levels

“…In adolescence, the disease often occurs in the long bone metaphysis of the extremities, such as the distal femur and the proximal tibia [ 4 , 5 ]. For the elderly, however, the predilection sites are diverse, which can also occur in the craniofacial region [ 6 ]. OSA has a high propensity to metastasize, specifically to the lungs, with more than 85% of patients developing lung metastasis at the time of initial treatment [ 7 ].…”