Assessing tumor angiogenesis in colorectal cancer by quantitative contrast-enhanced endoscopic ultrasound and molecular and immunohistochemical analysis

Background and Objectives: Data on contrast-enhanced endoscopic ultrasound (CE-EUS) for colorectal cancer (CRC) evaluation are scarce. Therefore, we aimed to assess the vascular perfusion pattern in CRC by quantitative CE-EUS and compare it to immunohistocliemical and genetic markers of angiogenesis. Patients and Methods: We performed a retrospective analysis of CE-EUS examinations of 42 CRC patients. before any therapy. CE-EUS movies were processed using a dedicated software. Ten parameters were automatically generated from the time-intensity curve (TIC) analysis: peak enhancement (PE), rise time (RT), mean transit time, time to peak (TIP). wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WIPI). wash-out AUC (WoAUC). and wash-in and wash-out AUC (WiWoAUC). The expression levels of the vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2 genes were assessed from biopsy samples harvested during colonoscopy. Microvascular density and vascular area were calculated after CD31 and CD105 immunostaining. Results: Forty-two CE-EUS video sequences were analyzed. We found positive correlations between the parameters PE, WiAUC, WiR. WIPI, WoAUC, WiWoAUC, and N staging (Spearman r = 0.437, r = 0.336, r = 0.462, r = 0.437, r = 0.358, and r = 0.378, respectively, P < 0.05), and also between RT and TTP and CD31 vascular area (r=0.415, and r=0.421, respectively, P< 0.05). VEGFR1 andVEGFR2 expression did not correlate with any of the TIC parameters. Conclusions: CE-EUS with TIC analysis enables minimally invasive assessment of CRC angiogenesis and may provide information regarding the lymph nodes invasion. However, further studies arc needed for defining Its role in the evaluation of CRC patients.