9577 Background: Pathologic events pertaining to the intracellular cell signaling pathway are now being recognized to be directly or indirectly responsible for oncogenic transformation in a variety of malignancies. Many drugs are now available which can block key steps of these signaling pathways. We sought to use IHC stains of previously stored sarcoma specimens to determine if expression of potential molecular targets (mTOR, p 70 S6 Kinase, ERK1/2, NF Kappa B) is present. Methods: Using tumor registry data, our three most common adult STS histopathologic subtypes were identified, and paraffin embedded tissue blocks representing these histologies were retrieved. Each block was reviewed for tissue adequacy. The blocks were cut and then stained with the aforementioned phosphorylated IHC stains (Cell Signal Technologies). Slides were graded on intensity of stain uptake (0–3+) and percentage of cells staining. A particular IHC stain was considered positive if 10% or more cells were stained 1+ or greater in intensity. Results: Seventeen Malignant Fibrous Histiocytomas (MFH), 20 Leiomyosarcomas (LMS) and 7 Liposarcomas were stained for the presence of p-mTOR, p-p70S6 Kinase, p ERK1/2, and p-NF Kappa B. Data for NF Kappa B will be presented at the meeting. The results are summarized in the table below. Conclusions: Pathways involving ERK appear to be active in more frequently diagnosed Sarcomas. Slightly more than half of the MFHs we studied expressed phosphorylated ERK1/2. Further exploration of this pathway, as well as mTOR, as potential targets of therapeutic intervention is indicated in STS. [Table: see text] No significant financial relationships to disclose.
Molecular targets and novel therapeutic avenues in soft tissue sarcoma
