[86] Immunohistochemical and Cytogenetic Analyses of FGF23, and Chondrogenic and Osteogenic Transcription Factor Expression in Phosphaturic Mesenchymal Tumor

A Kumagai, T Motoi, S Fukumoto, T Ushiku, A Yoshida, K Ohashi, M Fukayama, T Fukusato. Teikyo University School of Medicine, Tokyo, Japan; University of Tokyo, Tokyo, Japan; Toranomon Hospital, Tokyo, Japan

Background: Phosphaturic mesenchymal tumor (PMT) is a rare mesenchymal neoplasm arising from both bone and soft tissue, which induces oncogenic osteomalacia (OO) as a paraneoplastic syndrome. Recently, FGF23 secreted by tumor cells is identified as a cause of OO; however, the mechanisms underlying the overexpression of FGF23 and the true nature of PMT tumor cells remain to be elucidated.
Design: Eight PMTs (6 from bone and 2 from soft tissue) with known OO, including 6 cases of mixed connective tissue variant (MCT) and 2 cases of osteoblastic variant (OB), were studied. Cytogenetic analysis was performed in 4 examples of MCT by dual-color chromogenic in situ hybridization (CISH) using chromosome 12 centromere (CEN12) and FGF23 probes. FGF23 immunohistochemistry was undertaken, using two different antibodies. In order to better characterize PMT tumor cells, the expression status of essential transcription factors in chondrogenesis (Sox9) and osteogenesis (Runx2 and Osterix) were examined by immunohistochemistry (2+:positive cells>50%, 1+:positive cells<50%).
Results: Immunohistochemically, focal cytoplasmic staining of FGF23 was observed in all the PMTs, whichever antibody was used. No copy number gain or loss of FGF23 was detected by CISH; tetrasomy 12 was however focally observed in 3 of 4 cases. Five of 6 MCTs showed higher level of immunoexpression of RUNX2 (2+) than Osterix (1+); on the contrary, both OBs labeled more for Osterix (2+) than Runx2 (1+). Sox9 expression was significantly lower than RUNX2 in MCTs (1+: 5/6 cases, 0: 1/5 cases). No Sox9 expression was observed in either OB.
Conclusions: FGF23 is a useful immunohistochemical marker for the diagnosis of PMT. The CISH analysis suggests the overexpression of FGF23 occur by mechanisms other than direct copy number alteration of FGF23 gene, and that chromosomal instability involving chromosome 12 may play a role in MCT. The predominant expression of osteogenic markers may indicate that PMT possess an osteogenic potential that is only incompletely unfolded. Since Runx2 is known to be expressed prior to Osterix in bone development, the higher Runx2 expression level in MCT may reflect its remaining at earlier phase in osseous differentiation than OB.
Category: Bone & Soft Tissue

Monday, March 22, 2010 1:00 PM

Poster Session II # 3, Monday Afternoon

 

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