| Autor: |
O'Shannessy DJ; Department of Translational Medicine and Diagnostics, Morphotek Inc., Exton, PA., Somers EB; Department of Translational Medicine and Diagnostics, Morphotek Inc., Exton, PA., Chandrasekaran LK; HistoRx Inc. (A subsidiary of Genoptix Medical Laboratory, Inc.), Carlsbad, CA., Nicolaides NC; Department of Translational Medicine and Diagnostics, Morphotek Inc., Exton, PA., Bordeaux J; HistoRx Inc. (A subsidiary of Genoptix Medical Laboratory, Inc.), Carlsbad, CA., Gustavson MD; HistoRx Inc. (A subsidiary of Genoptix Medical Laboratory, Inc.), Carlsbad, CA. |
| Abstrakt: |
Tumor survival is influenced by interactions between tumor cells and the stromal microenvironment. One example is Endosialin (Tumor Endothelial Marker-1 (TEM-1) or CD248), which is expressed primarily by cells of mesenchymal origin and some tumor cells. The expression, as a function of architectural masking, of TEM-1 and its pathway-associated proteins was quantified and examined for association with five-year disease-specific survival on a colorectal cancer (CRC) cohort divided into training (n=330) and validation (n=164) sets. Although stromal expression of TEM-1 had prognostic value, a more significant prognostic signature was obtained through linear combination of five compartment-specific expression scores (TEM-1 Stroma, TEM-1 Tumor Vessel, HIF2α Stromal Vessel, Collagen IV Tumor, and Fibronectin Stroma). This resulted in a single continuous risk score (TAPPS: TEM-1 Associated Pathway Prognostic Signature) which was significantly associated with decreased survival on both the training set [HR=1.76 (95%CI: 1.44-2.15); p<0.001] and validation set [HR=1.38 (95%CI: 1.02-1.88); p=0.04]. Importantly, since prognosis is a critical clinical question in Stage II patients, the TAPPS score also significantly predicted survival in the Stage II patient (n=126) cohort [HR=1.75 (95%CI: 1.22-2.52); p=0.002] suggesting the potential of using the TAPPS score to assess overall risk in CRC patients, and specifically in Stage II patients. |
