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

// Chung-Ta Lee 1 , Yu-Chuan Huang 2, * , Liang-Yi Hung 2, 3, * , Nan-Haw Chow 1 , Pei-Fang Su 4 , Chung-Liang Ho 1 , Hung-Wen Tsai 1 , Yi-Lin Chen 1 , Shao-Chieh Lin 4 , Bo-Wen Lin 5 , Peng-Chan Lin 6 and Jenq-Chang Lee 5 1 Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan 2 Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan 3 Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan 4 Department of Statistics, College of Management, National Cheng Kung University, Tainan 70101, Taiwan 5 Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan 6 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan * These authors have contributed equally to this work Correspondence to: Chung-Ta Lee, email: lcta@mail.ncku.edu.tw Jenq-Chang Lee, email: leejc@mail.ncku.edu.tw Keywords: colorectal cancer, mucinous adenocarcinoma, serrated adenocarcinoma, CIMP, BRAF Received: December 14, 2016     Accepted: March 19, 2017     Published: April 04, 2017 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.