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

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.

Cemento-ossifying fibroma transforming to osteosarcoma

“…In terms of immunohistochemistry(IHC), SATB2 and MDM2 have been shown to differentiate the long bone OSs, including the small cell variant, from their malignant bone tumour mimickers, such as Ewing sarcomas 14. A study concluded that MDM2 is a useful diagnostic marker to differentiate jaw OS from benign FOLs of the jaw, especially in the case of low-grade transformed OS or high-grade transformed OS 15 16. In contrast, few studies have concluded that STAB2 is not a reliable diagnostic marker for distinguishing oral OS and FOLs of the jaw.…”

Up-regulation of NCAPG mediated by E2F1 facilitates the progression of osteosarcoma through the Wnt/β-catenin signaling pathway

“…Therefore, early diagnosis is of great significance for the treatment and prognosis of patients with osteosarcoma. Current studies have shown that molecules including Snail, MICA, RASSF1A, HER2, MMP-2, MMP-9, and SATB2 have a certain significance in the diagnosis of osteosarcoma ( 27 - 33 ). However, specific biomarkers for the diagnosis of osteosarcoma are still lacking.…”

Loss of SATB2 expression correlates with cytokeratin 7 and PD-L1 tumor cell positivity and aggressiveness in colorectal cancer

“…A recent murine study showed that colonic stem cell identity was lost when SATB2 expression was lost; inversely, the gain of SATB2 expression in small bowel stem cells leads to the conversion into the colonic phenotype 6 . In human pathology, SATB2-immunohistochemistry has gained importance over the last two decades as a marker of osteosarcoma 7 , 8 . SATB2 is constitutively expressed in the physiological colorectal mucosa and a majority of colorectal adenocarcinomas 9 – 14 and is widely used as a routine immunohistochemical marker indicating a colorectal origin to differentiate colorectal adenocarcinomas from other adenocarcinoma primaries.…”