Epigenetic Study for Expression of MUC4 in Low Grade Fibromyxoid Sarcoma
Atsuji Matsuyama, Ryo Shibuya, Fumie Kubota, Mitsuhiro Nakamoto, Masanori Hisaoka. University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan
Background: Low grade fibromyxoid sarcoma (LGFMS) is a rare but distinctive fibromyxoid variant of fibrosarcoma, and has been shown to have characteristic chromosomal abnormalities such as t(7;16)(q33;p11), resulting in the FUS-CREB3L2 fusion gene. Recent gene microarray and immunohistochemical analyses have shown that LGFMSs specifically expresses MUC4, a transmembranous glycoprotein. The MUC4 gene is located on 3q29, that is not involved in the FUS-CREB3L2 fusion gene, and the mechanism of the upregulationed MUC4 gene expression is unclear.
Design: We examined the immunohistochemical expression of MUC4 in 24 LGFMSs, in all of which FUS-CREB3L2 fusion had been identified, and 273 other soft tissue tumors of a wider variety than that examined in the previous studies. To evaluate the epigenetic regulation of the MUC4, a methylation status of the promoter CpG region of the MUC4 gene was examined by methylation-specific PCR (MSP).
Results: Immunohistochemically, 91% (22/24) of LGFMSs and 22% (6/27) of synovial sarcomas were positively reactive to MUC4. The MUC4 expression was noted diffusely in LGFMSs, whereas focal and predominant MUC4 expression was seen in an epithelial component of synovial sarcomas. The other soft tissue tumors examined were negative. The MSP analysis revealed the promoter CpG of the MUC4 gene was unmethylated in all the 12 LGFMSs examined including a MUC4-negative tumor, and in 11 of the 12 other soft tissue tumors including MUC4 -negative synovial sarcomas.
Conclusions: MUC4 is a sensitive and reliable immunohistochemical marker for distinguishing LGFMS from non-LGFMS tumors other than synovial sarcoma. The almost consistently but not specifically unmethylated promoter region of the MUC4 suggests an additional regulatory mechanism leading to the aberrant expression of MUC4 in LGFMSs and synovial sarcomas.
Category: Bone & Soft Tissue
Monday, March 4, 2013 1:00 PM
Poster Session II # 5, Monday Afternoon