Abstract B117: Expression of c-MET and related oncogenic signals in formalin-fixed paraffin-embedded human tumors

Abstract

Abstract Background: Hepatocyte growth factor (HGF) and its receptor tyrosine kinase c-MET are often dysregulated in cancer. Stimulation of the HGF/MET signaling pathway can lead to increased cell migration, proliferation, and angiogenesis and is associated with highly invasive malignant cancers. Oncogenic activation of the c-MET pathway occurs by gene amplification, mutation, or autocrine/paracrine stimulation. Methods: We have examined the expression of total c-MET and the active, phosphorylated forms of MET and associated cellular signals in a panel of solid human tumors by immunohistochemistry (IHC). Results: Total c-MET is expressed in a wide variety of human tumors including breast, lung, colorectal, pancreatic, liver, glial and testicular cancers. Phospho-MET (p-c-MET) and phospho-focal adhesion kinase (pFAK, a downstream signal of MET) are expressed in a subset of c-MET expressing tumors. Table 1 includes preliminary results. Conclusions: Detection of p-c-MET and p-FAK in archival formalin fixed paraffin embedded tumors by IHC staining is possible, and we have identified a subset of tumors where HGF/MET activation is evident. These tumors would be an important indication for c-MET targeted antitumor therapies. Table 1 Percentage of human tumors that express c-MET biomarkers Positive IHC Staining Tumors Total Tumor Type c-MET (N) p-c-MET (N) p-FAK (N) breast 96% (23) 61% (23) 65% (23) lung (NSCLC) 75% (36) 50% (36) 61% (36) colorectal 85% (20) 50% (20) ND pancreas 85% (55) 64% (53) 58% (55) Liver 91% (22) 14% (22) 18% (22) glioma 83% (18) 39% (18) 39% (18) Testis 65% (30) 23% (30) 45% (28) ND = not done Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B117.