SATB2 and MDM2 Immunoexpression and Diagnostic Role in Primary Osteosarcomas of the Jaw.

Adepitan A Owosho,Kehinde E Adebiyi,Temitope Kehinde,Grayson Cole,Kurt F Summersgill,Adeola M Ladeji,Jacob Palmer,Mofoluwaso A Olajide,Jeffrey A Vos,Olufunlola M Adesina,Toluwaniyin Okunade

doi:10.3390/dj10010004

Abstract

Primary osteosarcomas of the jaw (OSJ) are rare, accounting for 6% of all osteosarcomas. This study aims to determine the value of SATB2 and MDM2 immunohistochemistry (IHC) in differentiating OSJ from other jawbone mimickers, such as benign fibro-osseous lesions (BFOLs) of the jaw or Ewing sarcoma of the jaw. Certain subsets of osteosarcoma harbor a supernumerary ring and/or giant marker chromosomes with amplification of the 12q13–15 region, including the murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) genes. Special AT-rich sequence-binding protein 2 (SATB2) is an immunophenotypic marker for osteoblastic differentiation. Cases of OSJ, BFOLs (ossifying fibroma and fibrous dysplasia) of the jaw, and Ewing sarcoma of the jaw were retrieved from the Departments of Oral Pathology and Oral Medicine, Faculty of Dentistry, Obafemi Awolowo University and Lagos State University College of Medicine, Nigeria. All OSJ retrieved showed histologic features of high-grade osteosarcoma. IHC for SATB2 (clone EP281) and MDM2 (clone IF2), as well as fluorescence in situ hybridization (FISH) for MDM2 amplification, were performed on all cases. SATB2 was expressed in a strong intensity and diffuse staining pattern in all cases (11 OSJ, including a small-cell variant, 7 ossifying fibromas, and 5 fibrous dysplasias) except in Ewing sarcoma, where it was negative in neoplastic cells. MDM2 was expressed in a weak to moderate intensity and scattered focal to limited diffuse staining pattern in 27% (3/11) of cases of OSJ and negative in all BFOLs and the Ewing sarcoma. MDM2 amplification was negative by FISH in interpretable cases. In conclusion, the three cases of high-grade OSJs that expressed MDM2 may have undergone transformation from a low-grade osteosarcoma (LGOS). SATB2 is not a dependable diagnostic marker to differentiate OSJ from BFOLs of the jaw; however, it could serve as a valuable diagnostic marker in differentiating the small-cell variant of OSJ from Ewing sarcoma of the jaw, while MDM2 may be a useful diagnostic marker in differentiating OSJ from BFOLs of the jaw, especially in the case of an LGOS or high-grade transformed osteosarcoma.

Highlights

Osteosarcoma is the most common malignant primary bone tumor arising from mesenchymal osteoblasts that produce neoplastic osteoid or immature bone [1]
From other common jawbone mimickers. We investigated these in OSJ, benign fibro-osseous lesions of the jaw, and a primary Ewing sarcoma of the jaw
Low-grade osteosarcomas (LGOS) are characterized by plump/spindle cell stroma with low-to-moderate cellularity and well-differentiated anastomosing bone trabeculae, which can be confused with benign fibro-osseous lesions (BFOLs), such as ossifying fibroma and fibrous dysplasia, in the setting of a limited/small biopsy

Summary

Introduction

Osteosarcoma is the most common malignant primary bone tumor arising from mesenchymal osteoblasts that produce neoplastic osteoid or immature bone [1]. It commonly affects children and adolescents, typically involving metaphyses of long bones, such as the femur, tibia, and humerus. The predisposing conditions to osteosarcoma are Li-Fraumeni syndrome, congenital poikiloderma, prior radiation to bone, and bone diseases such as. Osteosarcoma can be classified as osteoblastic, chondroblastic, or fibroblastic. It can be classified as other, rarer forms, such as the small-cell variant, epithelioid, giant cell-rich, telangiectatic, and well-differentiated (low-grade intraosseous). The survival rate of osteosarcoma patients remains dismal, for patients that develop distant metastasis [5,8,9]

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