Abstract 2787
Background
The form of microsatellite instability (MSI) affecting tetranucleotide repeats known as EMAST (elevated microsatellite alterations at selected tetranucleotide repeats) has emerged as a new potential biomarker in multiple cancers. In colorectal cancer (CRC), the clinical implications and mutation spectrum of EMAST mutations remain inconclusive.
Methods
We evaluated 1,505 CRC cases using five EMAST markers (D20S82, D20S85, D8S321, D9S242 and MYCL1) and the Bethesda panel of MSI markers. Most commonly mutations involved in CRCs were identified by MassArray Assay and DNA repair genes were analyzed by Next-Generation Sequencing (NGS). Clinical characteristics and prognostic relevance were correlated with EMAST. SPSS software (version 16.0) was used to perform all statistical analyses.
Results
Tumors with EMAST-positivity were detected in 159 (10.6%) out of 1,505 CRC cases and associated with unique clinical features including female predominance (p = 0.017), higher prevalence of proximal colon tumors (p < 0.001), early stage tumors (p = 0.002), poorly differentiated tumors (p < 0.001), mucinous histology (p = 0.001), and MSI (p < 0.001) and higher incidence of mutations in PI3KCA (p = 0.003), BRAF (p < 0.001), TGFßR (p < 0.001), PTEN (p = 0.001), and AKT1 (p = 0.04) compared with EMAST-negative tumors. Compared with EMAST-positive alone or MSI-H alone tumors, EMAST-positive MSI-H tumors had higher rates of MSH6, MSH3, PMS2, and EXO1 gene mutation (p < 0.001, p = 0.005, p = 0.001, and p = 0.027) and MLH1, MSH6, and EXO1 gene mutation (p = 0.019, p = 0.005, and p = 0.046), respectively. Finally, EMAST-positivity was a good prognostic indicator in early stage CRC (p = 0.002) but not in late CRC (p = 0.920).
Conclusions
The EMAST defines a unique molecular subtype of CRC.
Clinical trial identification
Legal entity responsible for the study
Taipei Veterans General Hospital.
Funding
Taipei Veterans General Hospital, Ministry of Science and Technology.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.