132 Improved Detection of Murine Colonic Dysplasia by Fluorescent-Labeled Multimer Peptide Using NIR Wide-Field Endoscopy

G A A b st ra ct s round-shaped ones in tumor glands (stromal Twist1+cells, A/R = 2.69, glandular Twist1+ cells, A/R= 1.67, A/R p<0.001). TWIST1 expression in the stromal compartment was associated with chromosomal rather than microsatellite instability (84% vs. 68%, respectively; p= 0.05), advanced TNM stage (91% in stage IV vs 72% in stage I/II, p=0.001), and worse disease specific survival (p=0.007). None of 15 adenoma expressed TWIST1 in the neoplastic or stromal compartment (p<0.001 vs CRC). We assessed the neoplastic origin of TWIST1+ stromal cells in humanCRC by combining fluorescent in situ hybridization and immunohistochemistry. Chromosome 7 trisomy was traced in the nuclei of TWIST1+ stromal cells in 60% of CRC specimens harboring this chromosomal abnormality in tumor cells. In an orthotopic In Vivo murine model of rectal cancer, the Twist1+ cells CT26 with a mensenchymal signature, grew round-shaped in syngenic Balb/c mice, but switched to fibroblast shape once invading the stroma. Conclusion: TWIST1 plays a crucial role in maintaining EMT in human CRC. TWIST1-dependent up-regulation of MMP-1 is a newly identified mechanism activating matrix-degradation and cell invasiveness in EMT. By using TWIST1 as marker of invasive EMT cells, we first demonstrated that a fraction of peri-tumoral stromal cells, disguised as fibroblasts, are actually neoplastic. Based on our findings, CRC stroma should no longer be considered a mere recipient of non-neoplastic elements but rather a true incubator for cancer EMT-cells. Targeting TWIST1+ stromal cells might open new scenarios for interfering with cancer invasiveness, and with the metastatic cascade of CRC.