Progress in the Diagnosis and Treatment of Dedifferentiated Chondrosarcoma / 中国肿瘤临床

ABSTRACT

Dedifferentiated chondrosarcoma(DDCS)comprises approximately 10%of all chondrosarcomas and has the worst outcome with a 5-year survival of 10%.The preferred localizations are the femur,humerus and pelvis.DDCS represents a special form of chondrosarcoma characterized by the presence of well-differentiated cartilaginous component in juxtaposition with malignant mesenchymal tumor of high-malignancy grade.The diagnosis of DDCS is highly complicated,requiring detailed radiological and histopathological evaluation as well as precise bioptic technique.The dedifferentiated component is typically a high-grade sarcoma(usually grade 3 or 4),which can be either an osteosarcoma,a malignant fibrous histiocytoma or an anaplastic spindle cell sarcoma.In approximately one-third of the radiographs,one-third of the MR images,and one-half of the CT scans, the tumors demonskates bimorphic features.Recently,array-based comparative genomic hybridization(array-CGH)studies have been performed on frozen chondrosarcoma(including DDCS)specimens.There is a statistically significant association between high-grade tumor(grade Ⅲ and dedifferent ated)and the recurrent genetic deletions at 5q14.2～q21.3,6q16～q25.3,9p24.2～q12,and 9p21.3.One of the most commonly deleted regions of DDCS involved chromosome 9.Earlier investigations of DDCS showed p53 mutation and p53-LOH in the anaplastic component.It is also accompanied by Rt-LOH.P161NK4 and E-cadherin promotor methylation were observed in the low grade chondroid compartment of DDCS.While p161NK4,FHIT,and E-cadherin were methylated in highly malignant osteosarcomatous compartment of the tumor.Surgical resection of the tumor within wide or radical margins is the most important treatment.The value of neoadjuvant or adjuvant therapy remain uncertain.Several new drug targets have been identified and phase Ⅱ studies are currently ongoing.Current phase Ⅱ trials open for DDCS patients used the following medicineapomab(proapoptotic selective agonist of Ap02L/TRAIL death receptor),perifosine(serine/threonine kinase Akt inhibitor),dasatinib(multitargeted small-molecule tyrosine kinase inhibitor),and the combination of gemcitabine and docetaxel.More recently,several phase Ⅰ studies have reported incidental responses of DDCS to newer targeted agents,such as histone deacetylase and vascular endothelial growth factor antisense oligodeoxynucleotide.The prognosis for patients with DDCS remains poor. The poor prognosis of the DDCS is determined by nonchondroid high grade component caused by invasive growth and formation of metastases.Therefore,early diagnosis and prompt surgical treatment may improve the outcome.