Journal
JOURNAL FOR IMMUNOTHERAPY OF CANCER
Volume 6, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s40425-018-0341-y
Keywords
Prostate adenocarcinoma; Microsatellite instability; MSI; Promega; Capillary electrophoresis; Mismatch repair; NGS; Next-generation sequencing; mSINGS
Categories
Funding
- Prostate Cancer Foundation
- Department of Defense PCRP award [PC131820]
- DOD awards [W81XWH-15-1-0430, W81XWH-15-1-0562]
- Transformative Impact Award
- Prostate Cancer Biorepository Network (PCBN) awards [W81XWH-10-2-0056, W81XWH-10-2-0046]
- Institute for Prostate Cancer Research (IPCR)
- Pacific Northwest Prostate Cancer SPORE [P50CA97186, PO1 CA163227]
- Richard M. LUCAS Foundation
Ask authors/readers for more resources
Background: Microsatellite instability (MSI) is now being used as a sole biomarker to guide immunotherapy treatment for men with advanced prostate cancer. Yet current molecular diagnostic tests for MSI have not been evaluated for use in prostate cancer. Methods: We evaluated two next-generation sequencing (NGS) MSI-detection methods, MSIplus (18 markers) and MSI by Large Panel NGS (>60 markers), and compared the performance of each NGS method to the most widely used 5-marker MSI-PCR detection system. All methods were evaluated by comparison to targeted whole gene sequencing of DNA mismatch-repair genes, and immunohistochemistry for mismatch repair genes, where available. Results: In a set of 91 prostate tumors with known mismatch repair status (29-deficient and 62-intact mismatch-repair) MSIplus had a sensitivity of 96.6% (28/29) and a specificity of 100% (62/62), MSI by Large Panel NGS had a sensitivity of 93.1% (27/29) and a specificity of 98.4% (61/62), and MSI-PCR had a sensitivity of 72.4% (21/29) and a specificity of 100% (62/62). Conclusions: We found that the widely used 5-marker MSI-PCR panel has inferior sensitivity when applied to prostate cancer and that NGS testing with an expanded panel of markers performs well. In addition, NGS methods offer advantages over MSI-PCR, including no requirement for matched non-tumor tissue and an automated analysis pipeline with quantitative interpretation of MSI-status.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available