Screening for microsatellite instability in colorectal carcinoma: Practical utility of immunohistochemistry and PCR with fragment analysis in a diagnostic histopathology setting.

Screening for microsatellite instability in colorectal carcinoma: Practical utility of immunohistochemistry and PCR with fragment analysis in a diagnostic histopathology setting. Malays J Pathol. 2019 Aug;41(2):91-100 Authors: Cheah PL, Li J, Looi LM, Koh CC, Lau TP, Chang SW, Teoh KH, Mun KS, Nazarina AR Abstract Since 2014, the National Comprehensive Cancer Network (NCCN) has recommended that colorectal carcinoma (CRC) be universally tested for high microsatellite instability (MSI-H) which is present in 15% of such cancers. Fidelity of resultant microsatellites during DNA replication is contingent upon an intact mismatch repair (MMR) system and lack of fidelity can result in tumourigenesis. Prior to commencing routine screening for MSI-H, we assessed two commonly used methods, immunohistochemical (IHC) determination of loss of MMR gene products viz MLH1, MSH2, MSH6 and PMS2 against PCR amplification and subsequent fragment analysis of microsatellite markers, BAT25, BAT26, D2S123, D5S346 and D17S250 (Bethesda markers) in 73 unselected primary CRC. 15.1% (11/73) were categorized as MSI-H while deficient MMR (dMMR) was detected in 16.4% (12/73). Of the dMMR, 66.7% (8/12) were classified MSI-H, while 33.3% (4/12) were microsatellite stable/low microsatellite instability (MSS/MSI-L). Of the proficient MMR (pMMR), 95.1% (58/61) were MSS/MSI-L and 4.9% (3/61) were MSI-H. The κ value of 0.639 (standard error =0.125; p = 0.000) indicated s...
Source: Malaysian Journal of Pathology - Category: Pathology Tags: Malays J Pathol Source Type: research