[73] Mammalian Target of Rapamycin (mTOR) Is Constitutively Activated in Chordomas

CT Elkins, PD Zhang, T Scharschmidt, J Mayerson, OH Iwenofu. Ohio State University, Columbus, OH; Hospital of the University of Pennsylvania, Philadelphia, PA

Background: Chordomas are rare neuroaxial tumors that are locally aggressive and notoriously resistant to chemotherapy and radiation therapy. Recent data suggest that mammalian target of rapamycin pathway could play a role in the oncogenesis of chordomas and thus an important therapeutic target. Mammalian target of rapamycin (mTOR) is a serine/threonine kinase of the PI3K/AKT signaling pathway known to play an important role in cell growth and has been shown to be activated in various solid organ tumors and sarcomas. Several mTOR inhibitors are currently in clinical trials. However, expression of mTOR pathway-related genes in chordomas have not been completely evaluated on routine histologic material by immunohistochemical staining for phosphoribosomal S6 protein (p-s6rp), phospho-mTOR, p70S6K and p-AKT antibodies.
Design: 16 cases of chordoma were retrieved from the files at the Hospital of the University of Pennsylvania and the Ohio State University. Representative section from each case were stained with antibodies to p-AKT, p-mTOR, p-70S6k and p-S6rp (Ser235/236) using the DAKO autostainer. Staining was evaluated semiquantatively for both quantity (%: 0,≤10%, ≤25%, ≤50%, >50%) and intensity (0,1+ to 3+). Negative staining was defined as staining of 0 and 1+ <5%.
Results: In all the cases, the tumor cells showed intermediate to intense staining (2+ & 3+; 100%) with p-mTOR and p-70S6k antibodies; 14 of the 16 cases showed 2+ or 3+ p-aKT staining. P-S6rp staining was positive (2+ & 3+) in 14 of the 16 cases. The results are summarized in the table below:

pAKT/p-mTOR/p-70S6K/p-S6rp Expression in Chordomas
Stainsp-AKTp-mTORp-70S6Kp-S6rp
Chordomas (n=16) % staining9410010089



Conclusions: The results of a high level of expression for the p-AKT, p-mTOR, p-70S6k and pS6rp antibodies, are indicative of a high frequency of constitutive activation of PI3K/AKT/mTOR pathway in chordomas as previous suggested. Our study supports the use of mTOR inbihitors in treatment of chordoma and needs to be further evaluated in experimental models and clinical trials.
Category: Bone & Soft Tissue

Tuesday, March 23, 2010 9:30 AM

Poster Session III # 19, Tuesday Morning

 

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