MICRO-ARCHITECTURAL ALTERATIONS IN ENDOSCOPICALLY-NORMAL MUCOSA PROVIDES ACCURATE RISK STRATIFICATION FOR COLORECTAL NEOPLASIA

Abstract

Purpose: The “field effect” is frequently exploited for colorectal cancer (CRC) screening; however, the most common markers (i.e. the distal adenoma) lacks both sensitivity and positive predictive value. Micro-alterations in the colonocytes (i.e. the “field”) may reflect the earliest events in colon carcinogenesis although, to date, practical detection of these subtle changes have not been possible. We have pioneered optics for the detection of dysplasia in general (Nature 2000) and in the colon (Nature Med 2001). We have recently developed 4D-ELF, a new generation of light-scattering technology, that allows heretofore unattainable insights into the nano-scale cellular architecture (IEEE 2003). In experimental models, 4D-ELF analysis of uninvolved mucosa had unprecedented sensitivity for CRC risk (Gastroenterology 2004). The aim of this study was to evaluate the ability of 4D-ELF to predict neoplasia in humans. Methods: Forty-five patients undergoing colonoscopy had two mid-transverse colon biopsies from endoscopically normal mucosa. 4D-ELF analysis was performed on fresh tissue using our advanced light-scattering apparatus. Parameters that were evaluated included principal component 1 (PC1) and spectral slope. Patients were divided into high and low risk based on current and past colonoscopy findings (presence of adenoma or carcinoma). Results: PC1 and spectral slope were dramatically and highly statistically significantly altered in colonic neoplasia patients (high risk) when compared to those with normal colonoscopies (low risk) (see figure).Figure 1Conclusions: We demonstrate, for the first time, that micro-architectural changes in the endoscopically normal mucosa could predict the risk of colonic neoplasia. These parameters were markedly superior to any previously described biomarkers. This suggests that that 4D-ELF analysis may have potential applicability in CRC risk-stratification. [figure 1]