MDM2 and CDK4 Are Coexpressed in a Subset of Extraskeletal Osteosarcoma.
Akihiko Yoshida, Tetsuo Ushiku, Toru Motoi, Masashi Fukayama, Hitoshi Tsuda, Tatsuhiro Shibata. National Cancer Center, Tokyo, Japan; University of Tokyo, Japan; Teikyo University, Tokyo, Japan
Background: MDM2 and CDK4 gene amplification and the resultant protein overexpression is a characteristic of the majority of well-differentiated/dedifferentiated liposarcomas (WDLSs/DDLSs). Heterologous osteosarcomatous differentiation rarely occurs in WDLS/DDLS, and such a variant was previously shown to retain MDM2 and CDK4 immunohistochemical overexpression. Our recent encounter of a case of DDLS with massive osteosarcomatous differentiation, for which the diagnosis of extraskeletal osteosarcoma (ESOS) was seriously considered on initial biopsy, posed a question regarding the relationship between DDLS and ESOS. To clarify this, we undertook the immunohistochemical analysis of archival extraskeletal osteosarcomas.
Design: We retrieved 10 cases of extraskeletal osteosarcoma from the files of participating institutions (1960-2010). The tumor occurred in 7 men and 3 women, and the sites included retroperitoneum (n = 1), deep extremity (n = 4), superficial extremity (n = 3), pleura (n = 1), and ovary (n = 1). Nine cases were high-grade tumors; 1, low-grade. No cases showed histological/radiological evidence of coexistent liposarcomatous component. Visceral examples (n = 2) lacked coexisting carcinoma/mesothelioma or cytokeratin expression. A representative section of each case was immunostained with antibodies for MDM2 and CDK4. The results were expressed by staining intensity, which was graded from weak to strong, and by the extent of focal (1-10%) or diffuse (>10%) expression.
Results: Four (40%) cases were found to coexpress MDM2 and CDK4 mostly in a diffuse manner with moderate to strong intensity. They represented 50% of the 8 soft tissue ESOSs and 80% of the 5 deep-seated cases. One low-grade tumor was immunoreactive. The remaining 6 cases were negative for both the markers, and they included all the 3 superficially sited tumors and 2 visceral cases.
Conclusions: A subset of soft tissue ESOS, particularly when deep-seated, shows MDM2 and CDK4 coexpression. This subgroup may be related to DDLS despite the apparent lack of a coexisting liposarcomatous component.
Category: Bone & Soft Tissue
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 3, Tuesday Morning