Differential Expression of Proteins Regulating Lipogenesis in Liposarcoma
JE Pogoriler, AG Montag. University of Chicago Medical Center, Chicago
Background: PPAR-gamma, a transcription factor important in adipocyte differentiation, has been shown to be expressed in all subtypes of liposarcoma, and treatment with PPAR agonists induces differentiation of liposarcoma cells in vitro. These observations suggest that signaling pathways involved in adipocyte differentiation might also be important in liposarcomas. We hypothesized that signaling pathways that inhibit adipocyte differentiation would be more prominent in more aggressive tumor types.
Design: We constructed a liposarcoma tissue microarray that included well-differentiated, de-differentiated, myxoid, round-cell and pleomorphic liposarcomas. Using immunohistochemistry, we determined the expression of components of signaling pathways known to inhibit adipocyte development, including Wnt10b, ß-catenin, Notch1 and DLK1.
Results: Of 22 well-differentiated liposarcomas, none expressed Wnt10b or DLK1, and only 1 (5%) was positive for nuclear Notch 1. Well differentiated liposarcoma may progress to de-differentiated liposarcoma. Of 12 de-differentiated liposarcomas, 7 (58%) had nuclear Notch 1, and none expressed Wnt10b or DLK1. Of 16 myxoid liposarcomas, 1 (6%) expressed DLK1, 3 (19%) expressed Wnt10b, and 10 (62%) were positive for nuclear Notch 1. Myxoid liposarcoma may progress to a round cell phenotype, and 6 of the myxoid tumors positive for Notch 1 contained a transitional or round cell component. Of 8 round cell tumors, 1 (13%) expressed DLK, 3 (38%) expressed Wnt 10b and all 8 were positive for nuclear Notch 1. Pleomorphic liposarcomas are the most aggressive liposarcoma, and they had significantly higher rates of proliferation and greater nuclear staining of p53 than other tumor types. Of 12 pleomorphic liposarcomas, only 2 (17%) were positive for Wnt10b, but 10 (83%) were positive for DLK and nuclear Notch1. No tumors were positive for ß-catenin.
Conclusions: Overall, these results suggest that more aggressive, less differentiated types of tumors are more likely to express inhibitors of adipocyte differentiation, with Notch 1 activation frequently occurring as tumors progress to a more aggressive phenotype. In contrast, DLK was expressed only in pleomorphic tumors. Despite a role in inhibiting adipocyte differentiation during development, Wnt10b was not detected in the vast majority of liposarcomas.
Category: Bone & Soft Tissue
Monday, March 22, 2010 1:00 PM
Poster Session II # 12, Monday Afternoon