Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization

Developing a minimally invasive and cost-effective prescreening strategy for colon cancer is critical because of the impossibility of conducting colonoscopy on the entire at-risk population. The concept of field carcinogenesis, in which normal-appearing tissue away from a tumor has molecular and, consequently, nano-architectural abnormalities, offers one attractive approach to identify high-risk patients. In this study, we investigated whether the novel imaging technique partial wave spectroscopic (PWS) microscopy could risk-stratify patients harboring precancerous lesions of the colon, using an optically measured biomarker (L _d) obtained from microscopically normal but nanoscopically altered cells. Rectal epithelial cells were examined from 146 patients, including 72 control patients, 14 patients with diminutive adenomas, 20 patients with nondiminutive/nonadvanced adenomas, 15 patients with advanced adenomas/high-grade dysplasia, 12 patients with genetic mutation leading to Lynch syndrome, and 13 patients with cancer. We found that the L _d obtained from rectal colonocytes was well correlated with colon tumorigenicity in our patient cohort and in an independent validation set of 39 additional patients. Therefore, our findings suggest that PWS-measured Ld is an accurate marker of field carcinogenesis. This approach provides a potential prescreening strategy for risk stratification before colonoscopy.