Desmin expression in colorectal cancer stroma correlates with advanced stage disease and marks angiogenic microvessels

Protein from laser microdissected tumor and normal mucosa was analysed by two dimensional difference gel electrophoresis (2D DIGE) and mass spectrometry to determine differentially over expressed tumor proteins. Tumor over-expression of one such protein, desmin, was quantified using immunofluorescence staining in a larger cohort. Dual staining for desmin and vimentin, or desmin and von Willebrand factor, was performed to determine the cell type of interest.Desmin expression was significantly increased between stage I and III tumors, (P < 0.0001), and stage II and III tumors, (P < 0.0001). Strong focal desmin expression was found in stroma directly adjacent to carcinomatous glands and microvessels. These cells showed co-localisation of desmin and vimentin in close association with cells expressing VWF, indicating they were pericytes. Significantly higher levels of desmin-positive pericytes were observed in late stage tumors, consistent with increased angiogenesis.Pericyte coverage of vasculature is a marker of vessel maturation, hence desmin expression may have use as a marker for microvessel maturation. Clinical trials will be needed to determine its use in identifying tumors that will be less responsive to anti-angiogenic therapy.The staging of colorectal cancer (CRC) could be improved as up to 25% of patients deemed early stage (no regional lymph node or distant metastasis) relapse following presumed curative surgery [1]. This is likely caused by circulating tumor cells [2,3] or by established micro-metastatic disease in local lymph nodes or distant sites. Identification of a biomarker for more advanced disease in the primary tumor may result in down-staging the disease and thus identify a more appropriate selection of patients for increased surveillance and adjuvant therapy. Targeted therapy, such as anti-VEGF monoclonal antibody therapy, has shown a small but significant increase in progression-free and overall survival in a proportion of metastatic CRC patients