Microsatellite Instability (MSI) for endometrial cancer

Background

Patients with endometrial cancer can be screened for Lynch syndrome by both MSI testing and immunohistochemistry. MSI testing screens for the phenotype of microsatellite instability to identify patients who require further genetics referral and testing so that appropriate care can be given to affected patients to reduce the risks of a second malignancy.

Purpose of test

The MSI test compares the allelic profiles of five mononucleotide microsatellite markers (NR-21, BAT-26, BAT-25, NR-24 and MONO-27) generated by amplification of DNA from matching tumour and normal samples using a commercial MSI PCR kit (MSI Analysis System v1.2, Promega, Madison, WI, USA). Tumours are classified as MSI-high, MSI-low or MSS (microsatellite stable).

Expected test result

MSI-stable / MSI-low (1-shift) / MSI-high (2 or more shifts)

Caveats

DNA integrity and concentration must meet assay requirements. Low tumour content (<30%) may result in an inaccurate result. MSI PCR testing serves to identify the phenotype of microsatellite instability. MSI PCR does not identify the specific mismatch repair genes which are mutated. An MSI-high tumour does not equate to Lynch syndrome. MSH6-mutated tumours may not be MSI-high and such tumours will therefore not be identified by MSI testing alone. MSI-high tumours with retained MMR protein expression may have a POLE gene mutation.

Proficiency testing

College of American Pathologists proficiency testing programme.

Reference

McMeekin DS et al. Clinicopathologic significance of mismatch repair defects in endometrial cancer: An NRG Oncology/ Gynecologic Oncology Group Study. J Clin Oncol 2016; 34(25): 3062-8.