[74] Mammalian Target of Rapamycin (mTOR) Pathway Is Differentially Upregulated in Liposarcomas More Than Lipomas and Normal Fat

CT Elkins, T Scharschmidt, J Mayerson, G He, OH Iwenofu. Ohio State University, Columbus; Ohio State University, Columbus, OH

Background: The mammalian target of rapamycin (mTOR) is a protein kinase of the phosphatidylinositol 3-kinase (PI3K) signaling pathway that regulates cell growth and survival. The mTOR pathway is activated in various solid organ tumors and sarcomas, and is of importance because several mTOR inhibitors are currently on clinical trials. Phosphoribosomal S6 protein (p-S6rp) is a surrogate marker for mTOR pathway activation and has been shown to be predictive of tumor response to mTOR inhibition. This is the first study on the differential activation of the mTOR pathway in normal fat, lipomas and liposarcomas.
Design: 38 lipomatous lesions including normal fat (n=10), lipomas (n=10), and liposarcomas (n=18), including well differentiated liposarcoma, (n=10), myxoid/round cell liposarcoma (n=6) and pleomorphic liposarcoma (n=2) were retrieved form the case files of OSU. Standard sections were stained with anti-pS6rp (Ser 235/236, Cell Signaling Technologies, Danvers, MA, USA) using the DAKO autostainer. Staining was evaluated semiquantatively for both quantity (%: 0,≤10%, ≤25%, ≤50%, >50%) and intensity (1-3+). Negative staining was defined as staining of 0 or 1+ intensity of <5%.
Results: A high level of expression of p-s6rp was observed across the various subtypes of liposarcomas (LPS) with (89%; 16/18) 2-3+ staining intensity. The well differentiated LPS's had a positive rate of 80% (8/10 cases) while all cases of myxoid/round cell LPS (n=6) and pleomorphic LPS (n=2) were positive (100%) respectively. Lipomas showed an intermediate level of expression (60%), with the majority of cases showing 2+ expression in approximately 10% of tumor cells. Normal fat had a positive rate of 30%. The differential staining between the LPS's, lipomas and normal fat on chi-square analysis was statistically significant with p≤0.05≤0.001 respectively.

Phospho-S6 ribosomal protein expression in Liposarcomas, Lipomas and Normal Fat
Tumor typesPositiveNegativeTotal
Liposarcomas (n=18)16218
Lipomas (n=10)6410
Normal Fat (n=10)3710

Conclusions: The relative high expression of p-S6rp in malignant fat tumors compared to lipomas and normal fat is indicative of the differential activation of the mTOR pathway in liposarcomas with potential implication for the use of mTOR inhibitors for targeted therapy. Clinical trials are needed to validate the utility of these novel agents.
Category: Bone & Soft Tissue

Monday, March 22, 2010 1:00 PM

Poster Session II # 13, Monday Afternoon


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