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Updated: Aug 2, 2026
Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
Impact of Institutional Universal Microsatellite-Instability (MSI) Reflex Testing on Molecular Profiling Differences
Ellery Altshuler1, Aaron J Franke1, William Paul Skelton2
1Division of Hematology & Oncology, Department of Medicine, University of Florida, Gainesville, FL.
Introduction:
DNA mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer (CRC) is found in about 15% of early-stage diseases and 5% of metastatic diseases. We reviewed a large, single-institutional database after implementation of universal reflex dMMR/MSI-H testing in CRC to compare profiles of younger (≤50) and older (>50) patients.
Patients And Methods:
Between 2009 and 2017, all patients diagnosed with CRC at the University of Florida underwent reflex somatic tumor testing for dMMR by immunohistochemistry (MLH1, PMS2, MSH2, MSH6), MSI by PCR, and Next-Generation Sequencing. Statistical analysis was conducted with 2-sample comparison tests and logistic regression models.
Results:
There were 375 patients included in the final analysis. Patients were grouped as younger (ages ≤50 years-old; n = 80) or older (>50 years-old; n = 295). Compared to tumors from older patients, tumors from younger patients were less likely to be dMMR/MSI-H (12.5% vs. 21.4%, P = .013) and less likely to have a BRAF mutation (1.5% vs. 16.1%, P = .002). BRAF mutation status was highly associated with MMR status; BRAF-mutated tumors were 29.7 times more likely than BRAF-WT tumors to be dMMR/MSI-H (P = < .001, 95% CI 11.3-78.3).
Conclusions:
Tumors of younger patients were less likely than tumors of older patients to have a dMMR/MSI-H or BRAF mutation. Universal MMR/MSI testing in our dataset identified a relatively large population of older patients with sporadic CRC who were eligible for immunotherapy.
