Prevalence of elevated microsatellite alterations at selected tetranucleotide repeats in pancreatic ductal adenocarcinoma
Related Experiment Video
Updated: Feb 1, 2026
Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line
Published on: April 11, 2025
Taiki Mori1, Yasushi Hamaya1, Takahiro Uotani1
1First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) prognosis remains poor even after complete resection owing to no valuable biomarkers for recurrence and chemosensitivity. Tumors not expressing MSH3 show elevated microsatellite alterations at selected tetranucleotide repeats (EMAST). EMAST reportedly occurs in several tumors. In colorectal cancer (CRC), EMAST was reportedly correlated with 5-fluorouracil (5-FU) sensitivity. However, EMAST prevalence in PDAC and its significance as a prognostic biomarker are unknown. This study aimed to investigate EMAST prevalence in PDAC and the associations between EMAST and pathological factors, EMAST and prognosis, and EMAST and MSH3 expression via immunohistochemistry (IHC). We assessed 40 PDAC patients undergoing surgery. Genomic DNA was extracted from tumors and normal tissues. EMAST and microsatellite instability-high (MSI-H) were analyzed using five polymorphic tetranucleotide markers and five mononucleotide markers, respectively. Tumor sections were stained for MSH3, and staining intensity was evaluated via the Histoscore (H-score). Eighteen of 40 (45%) PDAC patients were EMAST-positive; however, none were MSI-H-positive. Clinicopathological characteristics including overall survival (OS) and recurrence-free survival (RFS) were not significantly different between EMAST-positive and EMAST-negative patients (P = 0.45, 0.98 respectively). IHC was performed to evaluate MSH3 protein expression levels for the PDAC tissue specimens. H-scores of EMAST-positive patients ranged from 0 to 300 (median, 40) and those of EMAST-negative patients ranged from 0 to 300 (median, 170). MSH3 protein was not significantly downregulated in EMAST-positive patients (P = 0.07). This study is a preliminary study and the number of cases investigated was small, and thus, study of a larger cohort will reveal the clinical implication of EMAST.
Insights
Pancreatic cancer (PDAC) patients with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) showed no significant difference in survival or MSH3 expression. Further research is needed to determine EMAST
Area of Science:
- Oncology
- Genetics
- Cancer Biomarkers
Background:
- Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to a lack of reliable biomarkers for recurrence and chemosensitivity.
- Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) are observed in tumors lacking MSH3 expression and have been linked to 5-fluorouracil sensitivity in colorectal cancer.
- The prevalence and prognostic significance of EMAST in PDAC remain largely unknown.
Purpose of the Study:
- To investigate the prevalence of EMAST in PDAC.
- To assess the association between EMAST and clinicopathological factors, prognosis (overall survival and recurrence-free survival), and MSH3 expression.
Main Methods:
- Analysis of EMAST and microsatellite instability-high (MSI-H) in tumor and normal tissues from 40 PDAC patients using specific polymorphic markers.
- Immunohistochemistry (IHC) was used to evaluate MSH3 protein expression levels, quantified by Histoscore (H-score).
- Statistical analysis to compare clinicopathological characteristics, survival outcomes, and MSH3 expression between EMAST-positive and EMAST-negative groups.
Main Results:
- EMAST was detected in 45% (18/40) of PDAC patients; none exhibited MSI-H.
- No significant differences were observed in overall survival (P=0.45) or recurrence-free survival (P=0.98) between EMAST-positive and EMAST-negative patients.
- MSH3 protein expression showed no significant downregulation in EMAST-positive PDAC patients (P=0.07), with varying H-scores in both groups.
Conclusions:
- EMAST is prevalent in PDAC but does not appear to be a significant prognostic biomarker for survival in this preliminary study.
- The association between EMAST and MSH3 expression requires further investigation in larger cohorts.
- This preliminary study highlights the need for larger-scale investigations to elucidate the clinical implications of EMAST in PDAC.
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