Format

Send to

Choose Destination
J Immunother Cancer. 2018 Apr 17;6(1):29. doi: 10.1186/s40425-018-0341-y.

Microsatellite instability in prostate cancer by PCR or next-generation sequencing.

Author information

1
Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
2
Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA.
3
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
4
Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
5
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
6
VA Puget Sound Health Care System, Seattle, WA, USA.
7
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
8
Department of Laboratory Medicine, University of Washington, Seattle, WA, USA. cpritch@uw.edu.

Abstract

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.

KEYWORDS:

Capillary electrophoresis; MSI; Microsatellite instability; Mismatch repair; NGS; Next-generation sequencing; Promega; Prostate adenocarcinoma; mSINGS

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center