M1939 COX-2 Polymorphisms in Colorectal Carcinogenesis: A Strategy for Individualized Chemoprevention

Abstract

development of multiple serrated polyps and lesser numbers of adenomas. Nine cancers and ninety-three polyps (39 common hyperplastic polyps (HP), 35 advanced serrated polyps comprising 27 SSA, 1 serrated adenoma (SA) and 7 mixed polyps (MP), and 19 traditional adenomas (TA)) from 31 patients were stained for MUC6. Staining was positive in 69% of SSA, 86% of MP, and negative in a single SA. Overall, staining was positive in 70% of advanced serrated polyps which was significantly greater than the level seen in common HP (70% vs 38%; P=0.0065). MUC6 staining, where present, was confined to the crypt bases. All TA and normal mucosa were negative. Four of nine CRC (44%) stained positive for MUC6 and 75% of these were proximal contrasting with 20% of distal CRC. There was no association between MUC6 expression by CRC and mismatch repair deficiency. More proximal serrated polyps stained positively for MUC6 than distal serrated polyps, 66% and 30% respectively (P=0.008). This study suggests that MUC6 lacks the specificity originally observed by Owens et al, with staining present in 38% of HP. Though our findings were obtained in Caucasian patients with HPS, they are consistent with those of Mochizuka and colleagues (Histochem Cell Biol 2007; 128:445-55) who found MUC6 expression was expressed in common HP and SSA but not in traditional SA or normal mucosa in a series of Japanese patients where HPS was not targeted. Our findings further demonstrate that the expression of MUC6 is significantly more frequent in lesions arising in the proximal colon, whether or not advanced morphology was observed. MUC6 is frequently expressed in SSAs and to a lesser extent in HP and therefore does not provide a surrogate marker for advanced morphology in serrated polyps. The correlation of MUC6 expression with proximal location may suggest that a subset of common serrated polyps in the proximal colon may be developmentally related to their more advanced counterparts.