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

Abstract

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.

Plasma-based microsatellite instability detection strategy to guide immune checkpoint blockade treatment

“…Previous literature showed that MSI-H and MSS cell populations may co-exist within the same MSI-H tumor and patients burdened with multiple tumors could also have discrete genotypes in different lesions, both of which are expected to be better captured by liquid biopsy. [37][38][39][40][41] Temporal Open access discordance may also have played a role since a previous study showed that tissue-blood concordance dropped from 100% to 60% as the time interval between tissue biopsy and blood draw increased from ≤2 weeks to >6 months. 42 The feasibility of predicting ICB efficacy by NGSdetermined bMSI has been explored previously.…”

Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: A systematic review and meta-analysis

“…Abbreviation: P, prospective study; R, retrospective study; PD-1, programmed death-1; PD-L1, programmed death ligand 1; PD-L2, programmed death ligand 2; TIL, tumor-infiltrating lymphocyte; TMB, tumor mutational burden; MSI, microsatellite instability; NA, not available. [24,31,32,[79][80][81] conversion between primary lesions and paired metastases. Nine different cancer types were considered among all eligible studies in this analysis, including fifteen for the non-small cell lung cancer, fourteen for breast cancer, nine for colorectal cancer, five for the kidney renal clear cell carcinoma, five for the head and neck squamous cell carcinoma, four for bladder cancer, two for melanoma, one for synovial sarcoma and one for cervical cancer.…”

“…Inconsistent TIL counts were reported in breast and lung tumours compared with their metastases [20,30]. High concordance of MSI status is found in primary colorectal cancers and their matched liver, lung, and distant lymph node metastases with a total incidence of 2À16% [31,32]. Although discordant status of these biomarkers between primary and metastatic sites has been extensively reported, results from different studies are yet controversial.…”

Mechanisms of Immune Escape and Resistance to Checkpoint Inhibitor Therapies in Mismatch Repair Deficient Metastatic Colorectal Cancers

“…In most tumors, the MSS status was identified in both primary and metastatic specimens, whereas among 46 primary MSI tumors, nine of them were classified as MSS when the metastatic lesion was tested. Interestingly, the discrepancy was mainly limited to peritoneal and ovarian metastases [ 242 ]. If MMR heterogeneity is now confirmed, the implications of this phenomenon in cancer progression and response to therapies are still unclear and need to be thoroughly investigated.…”