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Prediction of biological behavior and prognosis of colorectal cancer patients by tumor MSI/MMR in the Chinese population

Authors Yan WY, Hu J, Xie L, Cheng L, Yang M, Li L, Shi J, Liu BR, Qian X

Received 12 July 2016

Accepted for publication 13 October 2016

Published 8 December 2016 Volume 2016:9 Pages 7415—7424


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr Carlos E Vigil

Wen-Yue Yan,1,* Jing Hu,1,2,* Li Xie,2 Lei Cheng,2 Mi Yang,2 Li Li,2 Jiong Shi,3 Bao-Rui Liu,2 Xiao-Ping Qian1,2

1The Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 2The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 3Department of Pathology, Drum Tower Hospital, Medical School of Nanjing University, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Abstract: Colorectal cancers (CRCs) exhibiting microsatellite instability (MSI) have special biological behavior. The clinical predictors for MSI and its survival relevance for the Chinese population were still unclear. Seven hundred ninety-five CRC patients were retrospectively assessed. Mismatch repair (MMR) proteins (MSH2, MSH6, PMS1, and MLH1) expression was detected by immunohistochemistry using tumor tissues of all patients. DNA MSI status was analyzed by polymerase chain reaction in 182 samples randomly selected from the 795 cases. Among all CRC tumor tissues, 97 cases (12.2%) were with an MMR protein-deficient (MMR-D) phenotype, whereas 698 cases (87.8%) were with an MMR proteins intact (MMR-I) phenotype. A total of 21 (11.5%) CRCs were identified as having high microsatellite instability, 156 (85.7%) tumors were having microsatellite stability (MSS), and five (2.7%) were having low microsatellite instability. Importantly, MMR status was demonstrated to be moderately consistent with MSI status (κ=0.845, 95% confidence interval [CI] 0.721, 0.969). Unconditional logistic regression analysis revealed age, number of lymph node, tumor diameter, and tumor site as predictors for MSI with a substantial ability to discriminate different MSI status by area under curve of 80.62% using receiver operation curve. Compared with MMR-I, MMR-D was an independent prognostic factor for longer overall survival (hazard ratio =0.340, 95% CI 0.126, 0.919; P=0.034). MMR-D is an independent prognostic factor for better outcome. Our results may provide evidence for individualized diagnosis and treatment of CRC, but this will require further validation in larger sample studies.

Keywords: microsatellite instability, mismatch repair, sporadic colorectal cancer, clinicopathological features, prognosis

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