Serrated adenocarcinoma morphology in colorectal mucinous adenocarcinoma is associated with improved patient survival.

Chung-Ta Lee,Yi-Lin Chen,Hung-Wen Tsai,Nan-Haw Chow,Peng-Chan Lin,Yu-Chuan Huang,Chung-Liang Ho,Shao-Chieh Lin,Liang-Yi Hung,Bo-Wen Lin,Jenq-Chang Lee,Pei-Fang Su

doi:10.18632/oncotarget.16815

Chung-Ta Lee, Yi-Lin Chen + Show 10 more

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https://doi.org/10.18632/oncotarget.16815

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Journal: Oncotarget	Publication Date: Apr 4, 2017
Citations: 16	License type: cc-by

Affiliation: National Cheng Kung University

Abstract

Colorectal mucinous adenocarcinoma (MAC) and serrated adenocarcinoma (SAC) share many characteristics, including right-side colon location, frequent mucin production, and various molecular features. This study examined the frequency of SAC morphology in MACs. We assessed the correlation of SAC morphology with clinicopathological parameters, molecular characteristics, and patient prognosis. Eighty-eight colorectal MACs were collected and reviewed for SAC morphology according to Makinen's criteria. We sequenced KRAS and BRAF, assessed CpG island methylator phenotype (CIMP) frequency, and analyzed DNA mismatch repair enzyme levels using immunohistochemistry in tumor samples. SAC morphology was observed in 38% of MACs, and was associated with proximal location (P=0.001), BRAF mutation (P=0.042), CIMP-positive status (P=0.023), and contiguous traditional serrated adenoma (P=0.019). Multivariate analysis revealed that MACs without both SAC morphology and CIMP-positive status exhibited 3.955 times greater risk of cancer relapse than MACs having both characteristics or either one (P=0.035). Our results show that two MAC groups with distinct features can be identified using Makinen's criteria, and suggest a favorable prognostic role for the serrated neoplastic pathway in colorectal MAC.

Highlights

Mucinous adenocarcinoma (MAC) of the colorectum accounts for approximately 10% of colorectal cancers (CRCs) and is diagnosed when >50% of the tumor is composed of extracellular mucin pools containing malignant epithelia [1, 2]
serrated adenocarcinoma (SAC) morphology was observed in 38% of mucinous adenocarcinoma (MAC), and was associated with proximal location (P=0.001), BRAF mutation (P=0.042), CpG island methylator phenotype (CIMP)-positive status (P=0.023), and contiguous traditional serrated adenoma (P=0.019)
We showed that MAC with SAC morphology tended to grow in the proximal colon with a higher frequency of “serrated pathway carcinoma” molecular features, including BRAF mutations and CIMP-positivity than MACs without SAC morphology

Summary

Introduction

Mucinous adenocarcinoma (MAC) of the colorectum accounts for approximately 10% of colorectal cancers (CRCs) and is diagnosed when >50% of the tumor is composed of extracellular mucin pools containing malignant epithelia [1, 2]. MAC is more common in women; it presents in the right colon and is generally detected at more advanced stages than non-MAC colorectal cancers [3]. MACs exhibit a higher frequency of DNA www.impactjournals.com/oncotarget mismatch repair (MMR) defects, microsatellite instability (MSI) and RAS/RAF/MAPK pathway mutations than non-MACs, and a lower incidence of p53 mutations [6,7,8,9]. MACs more frequently exhibit a CpG island methylator phenotype (CIMP). This is characterized by CpG island hypermethylation in the promoter regions of carcinogenesisrelated genes, resulting in epigenetic silencing [6, 8, 10, 11]

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