Nationwide large-scale investigation of microsatellite instability status in more than 18,000 patients with various advanced solid cancers.

Abstract

803 Background: The recent success of immunotherapy in high-frequency microsatellite instability (MSI-H) and/or mismatch repair protein deficient (MMR-D) tumors now supports testing for MSI in all advanced solid tumors. We previously reported using the quasi-monomorphic variation range (QMVR), the MSI status can be determined without matched normal DNA (Bando H, et al. Cancer Sci. 2018). Here, we investigate the proportion of the MSI status across various advanced solid tumors by this method. Methods: The MSI analysis was performed centrally by CLIA-certified, CAP-accredited, the single laboratory using tumor DNA from formalin-fixed paraffin embedded (FFPE) tissues with the MSI test kit (FALCO), which includes fluorescent-labelled primers for co-amplification of five mononucleotide markers (NR-21, BAT-25, MONO-27, NR-24 and BAT-26). The MSI-H was defined as positive if 2 or more makers showed instable. Results: A total of 18,250 patients with advanced solid tumors were registered from Dec 2018 to Aug 2019, and the MSI status was confirmed in 18,088 patients (99%). Among them, 51.9% were male, with median of 62.0 y/o. Overall prevalence of the MSI-H was3.3% (2.3% in male and 4.5% in female); the highest was 16.2% (149/916) in endometrial cancer, followed by 13% (13/100) in small intestinal cancer, 5.9% (74/1277) in gastric cancer, 3.3% (236/7190) in colorectal cancer, 2.6% (4/154) in prostate cancer, 2.5% (20/806) in ovarian cancer, 2.1% (9/426) in cervical cancer, 1.6% (13/831) in biliary tract cancer, 1.5% (4/271) in hepatocellular carcinoma, 0.9% (16/1852) in pancreas cancer. Interestingly, among biliary tract cancers, all MSI-H cases were arising from gall bladder (13/152) but no other sites. High prevalence was observed in cancer of teens or twenties (7.9%) and over 80y/o (5.6%), compare with others (3.0%) in this study (p < 0.001, both). Conclusions: These data show the MSI-H advanced solid tumors are distributed across a much broader tumor spectrum, and confirm the clinical relevance of the screening in patients with most advanced solid tumors, which can select patients sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin.