Abstract Adenomas with high-grade dysplasia (HGD) are recognized to be harbingers of future neoplastic lesions and colonoscopy is repeated in a year. There is little data regarding the neoplastic potential of the colon bearing such lesions. We postulated that lesions >1cm, in contrast to their smaller counterparts, would progress through an adenoma-carcinoma sequence. Conversely, smaller sized lesions might have a greater propensity for recurrence since there may be a priori more biological aggressiveness. Methods: We used the Adnab-9 monoclonal anti-adenoma risk marker to investigate high risk patients with HGD adenomas. Immunohistochemistry on normal-appearing colonic mucosa, ELISA of effluent acquired during colonoscopy and fecal Western blotting and ELISA, the stool collected prospectively was performed. Results: 23 patients with HGD adenomas, the majority found on the index colonoscopy were evaluated (table). A trend existed for increased NSAID intake in the large HGD group 5/7 (71%) compared to 2/7 (29%) in the small (p=0.28) and for increased numbers of metachronous adenomas in the small HGD group. More had symptoms in the large HGD group (67%) compared to 40% in small (NSS). No small HGD lesion was associated with a field effect (FE) in contrast to 100% in those patients with large lesion HGD (p<0.01). Concurrence with location of FE with synchronous adenomas was 5/6 (83%) and 2/5 (40%) with metachronous polyps in those with large HGD (p=0.24). Conclusions: Small HGD lesions appear to progress by pathways beyond the purview of the adenoma carcinoma sequence characterized by the significant lack of a field effect. They arise in a colon that may be destined for greater than usual risk for CRN even than that seen with larger HGD lesions. Larger prospective studies should be undertaken to confirm these preliminary findings and determine the tumorigenic pathway but in the interim surveillance for smaller lesions should not be limited to a single 1 year of follow-up.ParameterLarge HGDSmall HGDAll HGDN131023Age x±sd (years)65.5±10.064.7±8.765.2±9.3%Race AA53.93043.5BMI30.3±7.127.9±6.229.3±6.6%Left-sided76.97073.9%TA/TVA/VA69.2/23.1/7.760/40/063/32.7/4.3Size x±sd (mm)21.5±13.76.7±3.115.1±12.8Follow-up yrs3.6±2.15.3±2.7(p=0.15)4.2±2.4Synchronous adenomas1.8±3.3 6/14 46.2%1.4±1.5 5/10 50%1.5±2.7 11/24 45.8%Metachronous adenomas1.3±1; 7/10 70%2.1±2.34* 4/7 57% (p=0.6)1.3±1.7 11/17 64.7%%Ad-9 WB+12.528.620FecalAdnab-92/8 (25%)2/7(28.6%)4/15(26.7%)Effluent Elisa+4/9(44.4%)2/7(28.6%)p=.66/16(38%)%Field Effect6/6 (100)**0/5 (0%)6/11(55.5%)**OR 0.007:CI 0.0001-.415;p=0.0022; *p=0.3 Note: F/U time NSS Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2903.