Externalization of saw-tooth architecture in small serrated polyps implies the presence of methylation of IGFBP7

Eisuke Kaji, Hideyuki Suzuki, Toshio Uraoka, Takehiro Tanaka, Jun Kato, Mitsuhiro Akita, Nobuya Ohara, Sakiko Hiraoka, Shunsuke Saito, Kazuhide Yamamoto

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1261-1270
Number of pages10
JournalDigestive Diseases and Sciences
Volume57
Issue number5
DOIs
Publication statusPublished - May 2012

Fingerprint

Polyps
Methylation
Tooth
Adenoma
Mutation
Microsatellite Instability
ras Genes
Colorectal Neoplasms
Genes
Neoplasms

Keywords

  • Endoscopy
  • IGFBP7
  • Serrated pathway
  • Sessile serrated adenoma

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Externalization of saw-tooth architecture in small serrated polyps implies the presence of methylation of IGFBP7. / Kaji, Eisuke; Suzuki, Hideyuki; Uraoka, Toshio; Tanaka, Takehiro; Kato, Jun; Akita, Mitsuhiro; Ohara, Nobuya; Hiraoka, Sakiko; Saito, Shunsuke; Yamamoto, Kazuhide.

In: Digestive Diseases and Sciences, Vol. 57, No. 5, 05.2012, p. 1261-1270.

Research output: Contribution to journalArticle

Kaji, Eisuke ; Suzuki, Hideyuki ; Uraoka, Toshio ; Tanaka, Takehiro ; Kato, Jun ; Akita, Mitsuhiro ; Ohara, Nobuya ; Hiraoka, Sakiko ; Saito, Shunsuke ; Yamamoto, Kazuhide. / Externalization of saw-tooth architecture in small serrated polyps implies the presence of methylation of IGFBP7. In: Digestive Diseases and Sciences. 2012 ; Vol. 57, No. 5. pp. 1261-1270.
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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.",
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T1 - Externalization of saw-tooth architecture in small serrated polyps implies the presence of methylation of IGFBP7

AU - Kaji, Eisuke

AU - Suzuki, Hideyuki

AU - Uraoka, Toshio

AU - Tanaka, Takehiro

AU - Kato, Jun

AU - Akita, Mitsuhiro

AU - Ohara, Nobuya

AU - Hiraoka, Sakiko

AU - Saito, Shunsuke

AU - Yamamoto, Kazuhide

PY - 2012/5

Y1 - 2012/5

N2 - 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.

AB - 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.

KW - Endoscopy

KW - IGFBP7

KW - Serrated pathway

KW - Sessile serrated adenoma

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