Microsatellite instability testing in Korean patients with colorectal cancer

Abstract

Microsatellite instability (MSI) testing is useful for identifying patients with hereditary nonpolyposis colorectal cancer and detecting sporadic colorectal cancer that develops through replication error pathways. A pentaplex panel is recommended by the National Cancer Institute for MSI testing, but simplified mononucleotide panels and immunohistochemistry of mismatch repair proteins are widely employed for convenience. This study was to evaluate the MSI status of colorectal cancer in Korean patients. This study included 1,435 patients with colorectal adenocarcinoma subjected to surgical resection. The pentaplex Bethesda panel was used for MSI testing. Seventy nine (5.5 %) carcinomas were classified as MSI-high (MSI-H) and 95 (6.6 %) as MSI-low (MSI-L). BAT-26 and BAT-25 were unstable in 73 and 75 of 79 MSI-H carcinomas, respectively. With the panel comprising these 2 mononucleotide markers, 72 carcinomas were diagnosed as MSI-H, compared to the Bethesda panel data (72/79, 91.1 %). In contrast, BAT-26 or BAT-25 were unstable in only 7 (7.4 %) of the 95 MSI-L tumors. In the panel with 2 dinucleotide markers, D17250 linked to p53 and D2S123 to hMSH2, detection rates were 89.9 % (71/79) for MSI-H and 80.0 % (76/95) for MSI-L carcinomas, compared to the Bethesda panel. Moreover, we compared the frequency of MSI tumor in our patients with those reported previously from Western countries. In conclusion, the frequency of MSI-H appears lower in colorectal cancer patients in Korea. A simplified panel for MSI testing with BAT-26 and BAT-25 seems not effective for the accurate evaluation of MSI status, particularly in MSI-L colorectal carcinomas, in our patients.

Loss of AT-Rich Interactive Domain 1A Expression in Gastrointestinal Malignancies

“…Our experiments revealed no significant association between MSI status and loss of ARID1A expression. In fact, the rate of MSI-H was relatively low, specifically, 1.7% (3/178) in CRC and 6.4% (14/233) in GC, which was markedly lower than that recorded in our previous reports [5.5% in CRC (79/1,435), and 11.7% in GC (60/515)] [21,30]. This may partly explain why we could not detect an association between loss of ARID1A expression and MSI status.…”

“…DNA extraction and polymerase chain reaction analyses using a DNA autosequencer (ABI 3730 genetic analyzer; Applied Biosystems, Foster City, Calif., USA) were performed as described previously [21]. Until 2006, cancers with alterations in BAT-26 were categorized as MSI-high (MSI-H) phenotype.…”

Metastatic Pattern of Stage IV Colorectal Cancer with High-Frequency Microsatellite Instability as a Prognostic Factor

“…Frequency of CRC with MSI-H is approximately 10-15% in Western countries, whereas that in Asia was reported to be 5.5-7.3% (18,31,32), lower than in Western countries. However, despite the small number of cases, there was a significant prognostic difference between MSI-H-HL and MSI-H-PM cases.…”

Clinicopathologic features of gastric cancer with synchronous and metachronous colorectal cancer in Korea: are microsatellite instability and p53 overexpression useful markers for predicting colorectal cancer in gastric cancer patients?

“…Normal DNA was extracted from the surrounding normal tissue. Five microsatellite markers (BAT-25, BAT-26, D2S123, D5S346, and D17S250), recommended by a National Cancer Institute (NCI) workshop on MSI, were used to analyze paired normal and tumor DNA [16]. Polymerase chain reaction (PCR) was performed using a DNA autosequencer (ABI 3730 genetic analyzer; Applied Biosystems, Foster City, CA, USA).…”

“…The size of each fluorescent PCR product was calculated using GeneMapper software (Applied Biosystems). Based on the guidelines of the NCI, cases positive for C2 markers were considered to show high-frequency MSI (MSI-H), while cases positive for \2 markers were considered to show low-frequency MSI (MSI-L), and cases with no MSI were defined as microsatellite stable (MSS) [16,17].…”