MicroRNA-200a Expression in Synovial Sarcoma Is Related to Epithelial Differentiation.
Toru Motoi, Arisa Kumagai, Akihiko Yoshida, Tetsuo Imamura, Toshio Fukusato. Teikyo University School of Medicine, Tokyo, Japan; Tokyo University, Japan; Teikyo University Hospital, Tokyo, Japan
Background: Synovial sarcoma (SS) is characterized by epithelial differentiation through mechanisms involving epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). Recently, microRNA (miR)-200 family was found to play key roles in EMT/MET during tumor metastasis and invasion mainly by the regulation of E-cadherin (ECAD). To test the hypothesis that miR-200 may contribute to epithelial differentiation in SS, we examined the expression of miR-200a, a main member of miR-200 family, in SS and other sarcoma types.
Design: Formalin-fixed paraffin-embedded samples of 8 surgical cases of SS were collected, including 3 biphasic and 5 monophasic fibrous variants. For comparison, 4 malignant peripheral nerve sheath tumors, 4 solitary fibrous tumors (SFTs), 2 clear cell sarcomas, 2 dermatofibrosarcomas protuberans, 2 pleomorphic malignant fibrous histiocytomas, and 1 epithelioid sarcoma were also studied. Following total RNA extraction, the expression level of mature miR-200a was measured by quantitative RT-PCR with relative quantification calibrated by a SFT sample. SS cases were analyzed for SYT-SSX 1/2 by RT-PCR. Epithelial differentiation was assessed by immunohistochemical expression of cytokeratin (AE1/AE3) and ECAD. Immunostaining was graded as 3+ (>=30%), 2+ (10%-<30%), 1+ (1%-<10%), and 0 (<1%).
Results: miR-200a was highly expressed in SS (fold change: 0.7-363.1, mean: 99.7) compared with other types of sarcoma (0.1-40.7, mean: 4.8) (t-test, p < 0.05). In SS, the expression level of miR-200a were correlated with the reactivity of AE1/AE3 (3+:2/8, 2+:1/8, 1+:3/8, 0:2/8) and ECAD (3+:1/8, 2+:1/8, 1+:1/8, 0:5/8) in spindle cell component. Two SSs with very low miR-200a level were negative for AE1/AE3 and ECAD. Four SSs harbored SYT-SSX1 and the remaining 4 showed SYT-SSX2. Although histological and genetic subtypes were not correlated with miR-200a expression status, a case of biphasic SS with predominantly epithelial component expressed high level of miR-200a.
Conclusions: The expression of miR-200a is tightly linked to epithelial differentiation in SS. miR-200a may regulate its target EMT/MET genes to induce this phenotypic change. In addition, miR-200a was differentially expressed in SS over other sarcoma types, and it can be utilized as a new diagnostic marker of SS showing true epithelial diffrentiation.
Category: Bone & Soft Tissue
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 19, Tuesday Morning