The Clinicopathological Features and Genetic Mutations in Gastric Cancer Patients According to EMAST and MSI Status

Abstract

Background: There has been no report regarding the clinicopathological features and genetic mutations regarding elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in gastric cancer (GC). Methods: The correlation among EMAST status, microsatellite instability (MSI) status, mutations of common GC-related genes and 16 DNA repair-associated genes, and the clinicopathological features were analyzed. Results: Among the 360 GC patients enrolled, there were 76 (21.1%) with EMAST+ tumors and 284 with EMAST− tumors, and 59 (16.4%) were MSI-high (MSI-H) tumors, and 301 were microsatellite stable (MSS) tumors. Patients with EMAST+ tumors exhibited an earlier pathological T category and had more genetic mutations in the PI3K/AKT pathway, ARID1A and DNA repair-associated genes than those with EMAST− tumors. Patients with MSI-H tumors have more genetic mutations in the PI3K/AKT pathway and DNA repair-associated genes than those with MSS tumors. In the subgroup analysis for MSI-H GC, EMAST+ tumors were associated with earlier pathological T and N categories, earlier TNM stages, higher frequency of DNA-repair-associated genetic mutations, and a better survival rate than EMAST− tumors. Conclusions: PI3K/AKT pathway mutations may play an important role in EMAST+ and/or MSI-H GC. EMAST+/MSI-H tumors seem to represent a different subtype of gastric cancer from EMAST−/MSI-H tumors.

Elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in gastric cancer: a distinct microsatellite instability type with potential clinical impact?

“…The overall frequency of EMAST (2+) was, with 17.8% of the resected tumours showing these alterations, in a similar range to that reported in other studies of GC and also of colorectal carcinomas, which used a comparable definition for EMAST and microsatellite markers for EMAST analysis as in our study [ 18 , 26 ].…”

“…EMAST has been described in several tumour entities including GC, with broad variation in incidence ranging from 8 to 60% in gastrointestinal tumours, which may be related in part to the lack of a standardised definition and marker panels used for the determination of EMAST [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. A partial overlap of EMAST with MSI‐H and also with the MSI‐L phenotype has been reported, and it is not clear if EMAST differentiates MSI‐H tumours into two subgroups with potential consequences for treatment with immune therapy and if EMAST alone represents a unique molecular subclass [ 15 , 17 , 18 , 19 , 20 ]. Furthermore, knowledge about EMAST particularly in GC is limited.…”

Characterization and clinical evaluation of microsatellite instability and loss of heterozygosity in tumor‑related genes in gastric cancer

“…At present, studies analyzing the prognostic value of MSI remain controversial ( 17 ). The present study investigated the association between MSI status of the B5 panel and prognosis (OS, n=176; DFS, n=177; the low number of samples for OS and DFS is because the follow-up information of some patients were lacking).…”

“…In GC, the association between MSI and clinical features remains ambiguous, which may be due to the arbitrary use of MS loci, which is mostly based on CRC studies to define MSI status in different studies, and these loci are not likely to be sufficient for making clinical decisions. Therefore, there is an urgent requirement to identify novel MS loci for the clinical guidance of GC ( 11 , 16 , 17 ).…”

Determinants of Response and Intrinsic Resistance to PD-1 Blockade in Microsatellite Instability–High Gastric Cancer

“…These clinicopathologic observations partly underlie immunogenicity and the clinical responsiveness to immune checkpoint inhibitor (ICI) therapy (1-3),( 4), (5,6). In gastric cancer (GC), MSI-H is observed in 9-22% of non-metastatic cases and in 3-14% of advanced cases (7,8), (9)(10)(11).…”