Assessing prognostic and therapeutic associations across EMAST, MSI, and MSS among African Americans colorectal cancer subtypes

Background: Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST), microsatellite instability-high (MSI), and microsatellite stability (MSS) represent distinct forms of genomic instability and characterize colorectal cancer (CRC) genotypes related to DNA mismatch repair (MMR) deficiency and proficiency. EMAST is reported with a higher prevalence among African American (AA) vs White rectal cancers. The full clinical significance and phenotype of EMAST and its relationship with tumor characteristics, treatment factors, and patient outcomes remain unclear. Aim: We compared clinical characteristics, treatment patterns, and survival outcomes across EMAST, MSI, and MSS genotypes among AA CRC patients, and evaluated whether these genotypes have distinct prognostic or therapeutic associations. Methods: We retrospectively analyzed 304 CRC patients at Howard University, the majority being from AAs. Patients' CRCs were assessed for EMAST, MSI, and MSS via fragment analysis. Clinical variables, including demographics, survival, tumor location, and treatment history, were compared across groups. Remission and recurrence outcomes were assessed. Statistical significance was determined using p-values provided in the dataset. Results: Patients with EMAST CRCs demonstrated higher overall[JC1] mortality when compared with patients with MSI and MSS CRCs (32% vs 18% vs 14%, respectively). The higher mortality between patients with MSI versus MSS CRCs may reflect a greater proportion of stage III tumors in the MSI vs MSS subgroup (n=14, 48.3% vs n=91, 39%) as advanced stage is strongly associated with poor survival. Patients with MSI CRCs demonstrated more right-sided tumors (46%) than patients with MSS (13%) or EMAST (15%) CRCs. Symptom-wise, gastrointestinal bleeding was the most frequent occurring in 25%, 19% and 12% of patients with MSS, EMAST, and MSI CRCs, respectively. Treatment-wise, chemotherapy was administered to 57%, 63% and 57% of patients with EMAST, MSI, and MSS CRCs, and 84%, 100%, 76%, respectively, were treated with radiotherapy. However, patient benefit was not equal based on the higher mortality of patients with EMAST CRCs. Demographic and clinical variables showed no significant differences (p>0.05) between patients with EMAST, MSS, and MSI CRCs. Similarly, we identified no differences among the 3 groups in overall survival or remission and recurrence rates (p>0.05). Conclusions : Patients with EMAST CRCs have the highest mortality despite similar treatment exposures and comparable demographic and clinical characteristics amongst our three groups. As expected, patients with MSI CRCs demonstrate a predominance of right-sided cancers. Overall, the EMAST genotype aligns with being a biological modifier that associates with poorer patient outcomes.