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Digestive Diseases and Sciences

, Volume 57, Issue 5, pp 1261–1270 | Cite as

Externalization of Saw-Tooth Architecture in Small Serrated Polyps Implies the Presence of Methylation of IGFBP7

  • Eisuke KajiEmail author
  • Toshio Uraoka
  • Jun Kato
  • Sakiko Hiraoka
  • Hideyuki Suzuki
  • Mitsuhiro Akita
  • Shunsuke Saito
  • Takehiro Tanaka
  • Nobuya Ohara
  • Kazuhide Yamamoto
Original Article

Abstract

Introduction

Serrated polyps have been considered to be precursors of colorectal cancer with microsatellite instability. However, the biological and/or morphological changes which occur during the course of serrated polyp to cancer remain to be elucidated.

Methods

Twenty-eight colorectal serrated polyps including five mixed polyps (MP) from 20 patients were observed by chromoendoscopy with magnification, and subsequently resected endoscopically. The presence of mutations in two genes (K-ras and BRAF) and the methylation status of six genes (MLH1-A, MLH1-C, ESR1, P16, SOCS1, and IGFBP7) were examined.

Results

The 28 polyps included 32 histological serrated lesions (22 sessile serrated adenomas [SSA], six hyperplastic polyps [HP], and four traditional serrated adenoma [TSA]-like lesions). BRAF mutation was frequently observed in SSAs (19/22), while K-ras mutation was dominant in HPs (5/6). The externalization of saw-tooth architecture in serrated polyps was endoscopically observed more frequently in those with high levels of IGFBP7 methylation (P = 0.03). Moreover, the endoscopic finding was observed in five of six small serrated lesions (<10 mm) which contained both BRAF mutation and high levels of IGFBP7 methylation. TSA-like lesions in small MPs demonstrated the endoscopic finding with no or little MLH1 methylation, while the counterparts in the mixed polyps had high levels of MLH1 methylation with relatively low levels of IGFBP7 methylation.

Conclusions

Our data suggests two distinct pathways may be involved in the early stages of the serrated pathway: one where MLH1 is primarily methylated, and a second where methylated IGFBP7 is associated with an externalization of saw-tooth architecture.

Keywords

Sessile serrated adenoma Serrated pathway Endoscopy IGFBP7 

Notes

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Eisuke Kaji
    • 1
    Email author
  • Toshio Uraoka
    • 2
  • Jun Kato
    • 1
  • Sakiko Hiraoka
    • 1
  • Hideyuki Suzuki
    • 1
  • Mitsuhiro Akita
    • 1
  • Shunsuke Saito
    • 1
  • Takehiro Tanaka
    • 3
  • Nobuya Ohara
    • 3
  • Kazuhide Yamamoto
    • 1
  1. 1.Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  2. 2.Department of EndoscopyOkayama University HospitalOkayamaJapan
  3. 3.Department of Pathology and OncologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan

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