Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2015; 21(33): 9749-9757
Published online Sep 7, 2015. doi: 10.3748/wjg.v21.i33.9749
Annexin A10 expression in colorectal cancers with emphasis on the serrated neoplasia pathway
Jeong Mo Bae, Jung Ho Kim, Ye-Young Rhee, Nam-Yun Cho, Tae-You Kim, Gyeong Hoon Kang
Jeong Mo Bae, Jung Ho Kim, Ye-Young Rhee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea
Jeong Mo Bae, Jung Ho Kim, Ye-Young Rhee, Gyeong Hoon Kang, Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, South Korea
Tae-You Kim, Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-799, South Korea
Author contributions: Bae JM, Kim TY and Kang GH designed the research; Bae JM, Kim JH, Rhee YY and Cho NY performed the research; Bae JM analyzed the data and wrote the paper.
Supported by Grant from Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Education, No. 2013R1A1A2059080; a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, No. HI13C1804; Priority Research Centers Program through the NRF funded by the Ministry of Education, Science and Technology, No. 2009-0093820; and the NRF grant funded by the Ministry of Science, ICT, and Future planning, No. 2011-0030049; a grant of the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea, No. HI14C1277.”
Institutional review board statement: This study was reviewed and approved by Institutional Review Board ofSeoul National University College of Medicine/Seoul National University Hospital (IRB No: H. 1502-029-647).
Informed consent statement: Because this study is a retrospective study with a minimal risk to patients, it was exempted from obtaining informed consent by the IRB.
Conflict-of-interest statement: The authors declare no conflict-of-interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Gyeong Hoon Kang, MD, Professor, Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, South Korea. ghkang@snu.ac.kr
Telephone: + 82-2-20723312 Fax: +82-2-7435530
Received: March 1, 2015
Peer-review started: March 2, 2015
First decision: March 26, 2015
Revised: April 11, 2015
Accepted: June 16, 2015
Article in press: June 16, 2015
Published online: September 7, 2015
Processing time: 190 Days and 0.3 Hours
Abstract

AIM: To validate the utility of Annexin A10 as a surrogate marker of the serrated neoplasia pathway in invasive colorectal cancers (CRCs).

METHODS: A total of 1133 primary CRC patients who underwent surgical resection at Seoul National University Hospital between January 2004 and December 2007 were enrolled. Expression of Annexin A10 was evaluated by immunohistochemistry using tissue microarray and paired to our findings on clinicopathologic and molecular characteristics of each individual. CpG island methylator phenotype was determined by MethyLight assay and microsatellite instability was determined by high performance liquid chromatography. KRAS and BRAF mutation status was evaluated by direct sequencing and allele-specific PCR. Univariate and stage-specific survival analyses were performed to reveal the prognostic value of Annexin A10 expression.

RESULTS: Annexin A10 expression was observed in 66 (5.8%) of the 1133 patients. Annexin A10 expression was more commonly found in females and was associated with proximal location, ulcerative gross type, advanced T category, N category and TNM stage. CRCs with Annexin A10 expression showed an absence of luminal necrosis, luminal serration and mucin production. CRCs with Annexin A10 expression were associated with CpG island methylator phenotype, microsatellite instability and BRAF mutation. In survival analysis, Annexin A10 expression was associated with poor overall survival and progression-free survival, especially in stage IV CRCs.

CONCLUSION: Annexin A10 expression is associated with poor clinical behavior and can be used a supportive surrogate marker of the serrated neoplasia pathway in invasive CRCs.

Keywords: Annexin A10; Serrated neoplasia pathway; CpG island methylator phenotype; Colorectal cancer; BRAF mutation

Core tip: Annexin A10 is considered a surrogate immunohistochemical marker for sessile serrated adenomas/polyps. We validated the utility of Annexin A10 as a surrogate marker of the serrated neoplasia pathway in invasive colorectal cancers (CRCs). Annexin A10 expression was associated with female sex, proximal location, ulcerative gross type, advanced TNM stage, serration and mucin production. CRCs with Annexin A10 expression were associated with CpG island methylator phenotype, microsatellite instability and BRAF mutation. In stage-specific survival analysis, Annexin A10 expression was associated with poor clinical outcome in stage IV CRCs. Annexin A10 can be used a supportive surrogate marker of the serrated neoplasia pathway.