التفاصيل البيبلوغرافية
| العنوان: |
Screening for microsatellite instability in colorectal carcinoma: practical utility of immunohistochemistry and PCR with fragment analysis in a diagnostic histopathology setting. |
| المؤلفون: |
Phaik-Leng CHEAH, Jing LI, Lai-Meng LOOI, Cing-Chai KOH, Tze-Pheng LAU, Siow-Wee CHANG, Kean-Hooi TEOH, Kein-Seong MUN, NAZARINA, Abdul Rahman |
| المصدر: |
Malaysian Journal of Pathology; Aug2019, Vol. 41 Issue 2, p91-100, 10p |
| مستخلص: |
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 value of 0.639 (standard error =0.125; p = 0.000) indicated substantial agreement between detection of loss of DNA mismatch repair using immunohistochemistry and the detection of downstream microsatellite instability using PCR. After consideration of advantages and shortcomings of both methods, it is our opinion that the choice of preferred technique for MSI analysis would depend on the type of laboratory carrying out the testing. [ABSTRACT FROM AUTHOR] |
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