Disguised Techniques To FARP1

5?ng/ml. Quantification of PAPP-A in metastatic melanoma patient sera did not reveal elevated levels as compared to normal. PAPP-A knockdown resulted in significant decrease in invasive capability of melanoma cells, with a statistically significant 60% reduction in invasion (paired t-test, p value?FARP1 in BRAFi resistant cells (upto 3 fold), along with up-regulation in expression of IGF1 receptor (IGFR1) and IGF receptor substrates (IRS1 & IRS2), indicating role Doxorubicin in vivo of PAPP-A in acquired resistance to BRAFi via modulation of IGF signalling. Conclusions: Our data suggests that PAPP-A proteolytic activity plays an important role in melanoma progression and treatment resistance to BRAF inhibitors. Targeting PAPP-A could be a novel therapeutic strategy to limit disease progression and holds a promise in overcoming resistance to BRAFi in melanoma patients. In addition, PAPP-A has a potential to be an important biomarker for IGF targeted therapy. S. Sutherland1, S. Henshall2, L. Horvath1,2,4, J. Kench2,3,4 1Sydney Cancer Centre, Royal Prince Alfred Hospital, Sydney, Australia, 2Garvan Institute of Medical Research, Sydney, Australia, 3Department of Cancer Diagnostic/Tissue Pathology, Royal Prince Alfred Hospital, Sydney, Australia, 4University of Sydney, Sydney, Australia Background: The PI3K pathway plays a significant role in advanced prostate cancer (PCa). Mouse models suggest that the downstream effector molecule mTOR is also important in the development of PCa and plays a pivotal role in precursor lesions such as prostatic intraepithelial neoplasia Obeticholic Acid (PIN). This study was conducted to determine the status of p-mTOR across the prostate cancer progression model by looking at expression in normal prostate tissue, proliferative inflammatory atrophy (PIA), an hypothesised precursor lesion to HGPIN, HGPIN and PCa. Expression of p-mTOR in PIA was also compared to expression in, non precursor, atrophic lesions of the prostate. Methods: Expression of p-mTOR was evaluated by immunohistochemistry on tissue microarrays constructed from 119 archival formalin-fixed paraffin embedded radical prostatectomy tissue specimens. Levels of expression were recorded as the percentage of positive epithelial cells multiplied by the intensity of staining scored as 0�C3. Results: p-mTOR expression was found to increase across the progression model with median staining in non-neoplastic samples 15 compared to 100 in PIA, 112.5 in HGPIN and 144 in cancer (P?