Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

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  • a VIP Region and
  • | b Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong, P. R. China;
  • | c Department of Pathology, School of Basic Medical Sciences, and
  • | d Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China; and
  • | e Department of Molecular Diagnostics,
  • | f Department of Colorectal Surgery, and
  • | g Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China.
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Background: Differences between the features of primary cancer and matched metastatic cancer have recently drawn attention in research. This study investigated the concordance in microsatellite instability (MSI) and mismatch repair (MMR) status between primary and corresponding metastatic colorectal cancer (CRC). Methods: Consecutive patients with metastatic CRC who had both primary and metastatic tumors diagnosed at our institution in January 2008 through December 2016 were identified. Immunohistochemistry was used to test the MMR status of both primary and matched metastatic tumors, and PCR analysis was performed to test MSI in patients with deficient MMR (dMMR) status. Results: A total of 369 patients were included. Of the 46 patients with MSI-high primary tumors, 37 (80.4%) also had MSI-high metastatic tumors, whereas 9 (19.6%) had microsatellite stable (MSS) metastatic tumors. A high concordance was found in patients with liver, lung, or distant lymph node metastases. Interestingly, the discrepancy was more likely to be limited to peritoneal (5/20) or ovarian (4/4) metastasis (chi-square test, P<.001). These organ-specific features were also found in the pooled analysis. Along with the change of MSI-high in primary cancer to MSS in metastatic cancer, lymphocyte infiltration decreased significantly (P=.008). However, the change did not influence survival; the median overall survival of MSI-high and MSS metastatic tumors was 21.3 and 21.6 months, respectively (P=.774). The discrepancy rate was 1.6% for patients with proficient MMR primary tumors. Conclusions: For patients with dMMR primary tumors, the concordance of MSI and MMR status in primary CRC and corresponding metastatic cancer is potentially organ-specific. High concordance is found in liver, lung, and distant lymph node metastases, whereas discrepancy is more likely to occur in peritoneal or ovarian metastasis. Rebiopsy to evaluate MSI-high/dMMR status might be needed during the course of anti–PD-1 therapy in cases of peritoneal or ovarian metastasis.

Submitted September 25, 2018; accepted for publication April 5, 2019.

Author contributions: Study concept and design: He, Hu, Shao, L.P. Xia. Data acquisition, analysis, or interpretation: He, Hu, Wang, Jiang, Lu, Zhang, Ding, Shao, L.P. Xia. Statistical analysis: He, Hu, Wang, L.P. Xia. Acquisition of funding: X.J. Xia, Shao, L.P. Xia. Administrative, technical, or material support: Rong, L. Yang, Xie, Y.Z. Yang, Qiu, Lu. Supervision: X.J. Xia, Shao, L.P. Xia. Drafting of manuscript: He, X.J. Xia, L.P. Xia. Critical revisions: all authors.

Disclosures: The authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article. The data in the study were deposited in the Research Data Deposit system of Sun Yat-sen University Cancer Center [RDDA2019001007].

Funding: This work was supported by grants from the Natural Science Foundation of Guangdong, China (2015A030313010), Science and Technology Program of Guangzhou, China (1563000305), the Guangdong Innovative and Entrepreneurial Research Team Program (2016ZT06S638), the Science and Technology project of Guangdong Province (2017A020215031), and National Natural Science Foundation of China (81773051, 81272641, and 81572409).

Correspondence: Liang-Ping Xia, MD, and Jian-Yong Shao, MD, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong 510060, P. R. China. Email:;

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