Consistent Amplification of FRS2 and MDM2 in Low-grade Osteosarcoma: A Genetic Study of 22 Cases With Clinicopathologic Analysis

  title={Consistent Amplification of FRS2 and MDM2 in Low-grade Osteosarcoma: A Genetic Study of 22 Cases With Clinicopathologic Analysis},
  author={Xin He and Zongguo Pang and Xian-liang Zhang and Ting Lan and Hui-jiao Chen and Min Chen and Hong Yang and Juan Huang and Yihua Chen and Zhang Zhang and Wenyi Jing and Ran Peng and Hongying Zhang},
  journal={The American Journal of Surgical Pathology},
Low-grade osteosarcoma (LGOS) encompasses low-grade central osteosarcoma (LGCOS) and parosteal osteosarcoma (POS). LGOSs are characterized by a supernumerary ring and giant rod chromosomes containing the 12q13-15 amplicon. The fibroblast growth factor receptor substrate 2 (FRS2) gene is located close to MDM2 and CDK4. Recent studies identified consistent amplification of FRS2 gene in atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma. The aim of this… 
Genomic coamplification of CDK4/MDM2/FRS2 is associated with very poor prognosis and atypical clinical features in neuroblastoma patients
Genomic profiles of 628 NB samples analyzed by array‐comparative genome hybridization were re‐examined to identify gene amplifications other them MYCN amplification and the association of FRS2 gene expression with NB patient outcome using the public R2 Platform was evaluated.
MDM2 Gene Amplification and Expression of MDM2 and CDK4 are Rare in Ossifying Fibroma of Craniofacial Bones
While focal MDM2 and CDK4 nuclear expression may be detected in a minority of ossifying fibromas, this expression does not correlate withMDM2 amplification, and the detection of this genetic abnormality should continue to raise concern for osteosarcoma.
Novel NTRK3 Fusions in Fibrosarcomas of Adults
The clinicopathologic and genetic spectrum of sarcomas associated with NTRK fusions are expanded, and it is suggested that CD34-positive fibrosarcoma of bone and soft tissue could be a good candidate for N TRK testing.
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  • 2019
This review will summarize several of the important molecular findings in adipocytic tumors that have been described over the past 10 years.
Genetic characteristics and molecular diagnostics of bone tumors
A focused review concentrating on the molecular genetic features of bone tumors with specific, recurrent genetic alterations that make them appealing targets for directed ancillary testing by conventional or molecular techniques is provided.
Is Chemotherapy Associated with Improved Overall Survival in Patients with Dedifferentiated Chondrosarcoma? A SEER Database Analysis
Lack of clear benefit from perioperative chemotherapy in dedifferentiated chondrosarcoma argues that it should be used only after careful consideration, and ideally in the context of a clinical trial.
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Differences in MDM2 amplification profiles among liposarcomas could help further define and predict progression to high-grade neoplasia.
MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone
In conclusion, immunohistochemical expression of MDM2 and CDK4 is specific and provides sensitive markers for the diagnosis of low-grade osteosarcomas, helping to differentiate them from benign fibrous and fibro-osseous lesions, particularly in cases with atypical radio-clinical presentation and/or limited biopsy samples.
Amplification of FRS2 and activation of FGFR/FRS2 signaling pathway in high-grade liposarcoma.
It is found that FRS2 and FGFRs proteins are highly expressed and functional in three high-grade liposarcoma cell lines: FU-DDLS-1, LiSa-2, and SW872, and the FGFR selective inhibitor NVP-BGJ-398 significantly inhibited the growth of F U-DD LS-1 and Li Sa-2 cells with a concomitant suppression of FGFR signal transduction.
Immunohistochemical analysis of MDM2 and CDK4 distinguishes low-grade osteosarcoma from benign mimics
MDM2 and CDK4 immunostains reliably distinguish low-grade osteosarcoma from benign histological mimics, and their combination may serve as a useful adjunct in this difficult differential diagnosis.
MDM2 and CDK4 Immunohistochemical Coexpression in High-grade Osteosarcoma: Correlation With a Dedifferentiated Subtype
The data suggest that MDM2 and CDK4 coexpression in high-grade osteosarcomas is sensitive and specific to those that progressed from low-grade fractures, and immunohistochemistry may help identify this dedifferentiated subgroup to facilitate accurate subclassification.
Clinical outcome of low-grade central osteosarcoma and role of CDK4 and MDM2 immunohistochemistry as a diagnostic adjunct
  • D. JeonJ. Koh Soo‐Yong Lee
  • Medicine
    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association
  • 2015
The diagnosis of LCOS is challenging; however, if it is properly diagnosed, there is a high chance of a cure with wide excision alone, and positive immunostaining for CDK4 or MDM2 may be used as a diagnostic adjunct, although negative immunostained cannot rule out this tumor.
Characterization of the 12q15 MDM2 and 12q13‐14 CDK4 amplicons and clinical correlations in osteosarcoma
Coamplification of MDM2 and CDK4 in two separate amplicons occurs frequently in parosteal OS and less so in classical high‐grade OS.
Analysis of 12q13-15 Genes in Parosteal Osteosarcoma
SAS and CDK4 genes were found to be amplified fourfold in two Grade II tumors and in one dedifferentiated tumor, which might suggest a possible role of the chromosome 12 genes in the pathogenesis of parosteal osteosarcoma.