Evaluation of the Three Customized MSI Panels to Improve the Detection of Microsatellite Instability in Gastric Cancer

Abstract

The increased sensitivity to detect MSI-unstable tumors with customized panels including BAT40 and D18S34 indicates that precise MSI screening to discriminate MSI-H from MSS and MSI-L may be feasible for gastric cancer.

Genetic and histological subtypes of gastric cancer reviewed, particularly emphasising on microsatellite instability and E-cadherin gene mutation

“…II) [30,31]. A standard test for MSI, also known as the Bethesda panel, was proposed at the National Cancer Institute in 1997 but also customized panels are used which precisely indicate MSI [24,32,33]. This is a panel consisting of two mononucleotide repeats (BAT25, BAT26) and three dinucleotide repeats (D2S123, D5S346, D17S250) [22].…”

Prognostic and predictive biomarkers in oesophagogastric cancer

“…However, even with FLOT, 5-year overall survival reaches only 45%. Other attempts such as the use of preoperative chemotherapy combined with postoperative chemoradiotherapy in the CRITICS trial or the addition of targeted treatment such as bevacizumab in the ST03 trial did not improve overall survival compared to existing standard treatment regimens for patients with resectable GC (59,60).…”

“…Eight (13%) studies investigated KRAS amplification in addition to KRAS mutations with contradictory results. Three studies found that the incidence of KRAS amplification varied between 5% and 9% but was higher than that of KRAS mutation in GC (between 0% and 4%) (59,68,80…”

“…A recent study suggested that KRAS amplifications contribute to the activation of KRAS in GC (80) and that activation by KRAS amplification may account for the low incidence of KRAS mutations in GC compared to other types of cancer (59). However, the results from studies comparing the incidence and relationship of KRAS mutations (0-10%) and KRAS amplifications (1-9%) in GC remain contradictory (48,59,67,68,79,80,87). However, three studies seem to indicate that KRAS amplifications and mutations are mutually exclusive (48,79,80) suggesting a need to screen GC patients for both KRAS mutations and amplifications.…”

“…Discrepancies in the frequency of MSI-H amongst studies could be related to different definitions of MSI-H (32), as well as differences in location (28) and number of microsatellite loci tested (35). Recent studies in GC suggest that a mononucleotide and dinucleotide markers different to those included in the so-called Bethesda panel might improve accuracy and sensitivity of MSI testing in GC (58,59).…”