Elevated microsatellite alterations at selected tetranucleotides in early‐stage colorectal cancers with and without high‐frequency microsatellite instability: same, same but different?

Abstract

Microsatellite instability (MSI) is associated with better prognosis in colorectal cancer (CRC). Elevated microsatellite alterations at selected tetranucleotides (EMAST) is a less‐understood form of MSI. Here, we aim to investigate the role of EMAST in CRC±MSI related to clinical and tumor‐specific characteristics. A consecutive, population‐based series of stage I–III colorectal cancers were investigated for MSI and EMAST using PCR primers for 10 microsatellite markers. Of 151 patients included, 33 (21.8%) had MSI and 35 (23.2%) were EMAST+, with an overlap of 77% for positivity, (odds ratio [OR] 61; P < 0.001), and 95% for both markers being negative. EMAST was more prevalent in colon versus rectum (86% vs. 14%, P = 0.004). EMAST+ cancers were significantly more frequent in proximal colon (77 vs. 23%, P = 0.004), had advanced t‐stage (T3–4 vs. T1–2 in 94% vs. 6%, respectively; P = 0.008), were larger (≥5 cm vs. <5 cm in 63% and 37%, respectively; P = 0.022) and had poorly differentiated tumor grade (71 vs. 29%, P < 0.01). Furthermore, EMAST+ tumors had a higher median number of harvested lymph nodes than EMAST− (11 vs. 9 nodes; P = 0.03). No significant association was found between EMAST status and age, gender, presence of distant metastases or metastatic lymph nodes, and overall survival. A nonsignificant difference toward worse survival in node‐negative colon cancers needs confirmation in larger cohorts. EMAST+ cancers overlap and share features with MSI+ in CRC. Overall, survival was not influenced by the presence of EMAST, but may be of importance in subgroups such as node‐negative disease of the colon.

MSI‐L/EMAST is a predictive biomarker for metastasis in colorectal cancer patients

“…MSI analysis was performed using a panel of three mononucleotide markers: BAT‐25, BAT‐26, and NR‐27 and EMAST analysis was performed using a panel of five tetranucleotide markers: D20S82, D20S85, D9S242, D8S321, and MYCL1. Polymerase chain reaction (PCR) was performed with previously described primers (Mojarad et al, ; M. M. Watson et al, ) without fluorescent labels. Amplification reactions (25 μl) were prepared subjected to PCR amplification: Initial incubation at 95°C for 5 min, followed by 35 cycles of 95°C for 40 s, 62°C for 40 s, and 72°C for 40 s, and a final incubation at 72°C for 5 min.…”

Correlation of Blood T-Cells to Intratumoural Density and Location of CD3+ and CD8+ T-Cells in Colorectal Cancer

“…However, there is a link between MSI and immune response in that previous studies have found that patients with MSI have a higher percentage of CD8 + T-cells, but a lower percentage of CD4 + T-cells in tumour compared to those with microsatellite stable (MSS) disease (16). Another form of MSI includes elevated microsatellite instability at selected tetranucleotide repeats (EMAST) (17), which has been associated with a higher density of CD8 + at tumour nests (18) and was included together with MSI in this study for comparison.…”

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

“…In colorectal cancer, the incidence of EMAST was similar to that of MSI and was approximately 20%-40%; EMAST+ tumors were associated with the MSI-H phenotype and more frequently located in the colon than in the rectum [5,6]. However, in non-small cell lung cancer [7], the incidence of EMAST was higher than that of MSI (42.9% vs. 16.3%), and there was no association between the incidence rates of EMAST and MSI.…”

“…However, in non-small cell lung cancer [7], the incidence of EMAST was higher than that of MSI (42.9% vs. 16.3%), and there was no association between the incidence rates of EMAST and MSI. The correlation between EMAST status and patient survival in cancer is still controversial [5][6][7][8]. Consequently, there is a need to investigate the correlation among EMAST status, MSI status, genetic alterations, and clinicopathological features in GC patients.…”