683 Molecular Features of Colorectal Polyps Presenting Kudo's Type II Mucosal Crypt Pattern

Abstract

Molecular Features of Colorectal Polyps Presenting Kudo’s Type II Mucosal Crypt Pattern Kensuke Shinmura*, Kazuo Konishi, Yutaro Kubota, Yuichiro Yano, Hisako Nozawa, Atsushi Katagiri, Takashi Muramoto, Yoshiya Kobayashi, Toshihiro Kihara, Masayuki Tojo, Kenichi Konda, Teppei Tagawa, Toshiko Yamochi, Fumio Takimoto, Hitoshi Yoshida Division of Gastroenterology, Department of Medicine, Showa University, Tokyo, Japan; Department of Pathology, Showa University, Tokyo, Japan Background & Aims: Hyperplastic polyp (HP), sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA) are thought to be precursor lesions of serrated pathway. However, hyperplastic mucosal crypt patterns (so-called Kudo’s type II) are frequently observed in these lesions under chromoendoscopy. We hypothesized that there are biological or molecular differences among the serrated polyps (SPs) with hyperplastic crypt pattern and that these features are associated with their different pathways of progression to CRC. To test this hypothesis, we evaluated the molecular features of SPs with hyperplastic crypt pattern. Methods: We examined the clinicopathological and molecular features of 136 SPs with hyperplastic [stellar or papillary pits] crypt pattern that were resected endoscopically at Showa University Hospital from April 2005 to November 2011. We investigated the frequency of mutations of KRAS and BRAF; microsatellite instability (MSI); and CpG island methylator phenotype (CIMP), including the methylation of two or more CIMP-related genes (MINT1, 2, 31, p16, and MLH1). HPs were classified into microvesicular HP (MVHP), goblet cell-rich HP (GCHP), and mucin-poor HP (MPHP) variants on the basis of WHO classification. Results: 136 SPs with hyperplastic pattern comprised 81 serrated neoplasias (SNs) (21 TSAs, 60 SSAs), 43 MVHPs and 12 GCHPs. TSAs and SSAs were frequently located in the proximal colon, compared to others (P 0.01). We found no significant difference in the frequency of BRAF mutation among SPs except GCHP (57% for TSAs, 54% for SSAs, 49% for MVHPs and 9% for GCHPs). Furthermore, a significant difference was observed in the frequency of CIMP between TSAs or SSAs and GCHPs (52% for TSAs, 48% for SSAs, 30% for MVHPs and 0% for GCHPs) (P 0.05). When we classified SNs and MVHPs into proximal and distal lesions, proximal lesions had a macroscopically superficial appearance, whereas distal lesions had a protruding appearance (P 0.01). Moreover, the frequency of CIMP was significantly higher in the proximal than the distal lesions (55% vs. 16%) (P 0.05). Conclusions: We observed distinct molecular features between proximal and distal SPs with hyperplastic crypt pattern. Proximal SPs with hyperplastic pattern may develop from MVHPs through SSAs/TSAs to colon cancers.