(P 199) CHARACTERISTICS OF AN IMMUNOHISTOCHEMICAL AND MOLECULARLY DISCORDANT POPULATION OF GIST PATIENTS: A SINGLE CENTER RETROSPECTIVE REVIEW

Objective: CD117, the immunohistochemistry (IHC) marker for protein expression of KIT or the c-KIT proto-oncogene, is expressed in greater than 90% of gastrointestinal stromal tumors (GIST), with platelet-derived growth factor receptor alpha (PDGFRA) mutations also showing variable CD117 expression. However, 10-27% of CD117-expressing GIST tumors do not have detectable KIT or PDGFRA mutations on molecular testing. There is limited data in the literature describing outcomes of patients (pts) with this discordance in IHC and molecular results. Our objective was to evaluate this population of patients with CD117 expression and negative KIT/PDGFRA mutations.

Methods: We performed a retrospective chart review of consecutive pts seen at the University of Virginia with a tissue diagnosis of GIST between 1/1/2018 and 6/1/2025 who also had molecular testing data available. We analyzed patient- and disease-related characteristics within this cohort. Descriptive statistics were used.

Results: Of 40 pts in our total cohort, 45% were male, median age was 68 years, 22.5% were stage IV, 30% originated in the small bowel, and 55% had a moderate to high risk of recurrence at the time of diagnosis. 10 pts (25%) had CD117 positivity but negative molecular testing for KIT/PDGFRA mutations. Within this discordant cohort, 50% were male, median age was 69.5 years, 10% were stage IV, 50% originated in the small bowel, and 30% had a moderate to high risk of recurrence at the time of diagnosis. Median overall survival (OS) was unable to be calculated as > 50% of pts are still living.

Conclusion: Higher representation of small bowel GIST (50 vs 30%), NF1 mutations (50 vs 15%), CDKN2A deletion (10 vs 7.5%) and FH mutations (10 vs 2.5%) were seen in our population of pts with discordant IHC and molecular testing compared to the concordant cohort. Overall survival remains high in this group despite potentially higher risks of recurrence. Larger studies are needed to further elucidate the outcomes of this population.

Molecular and Patient Data for our IHC/Molecular Testing Concordant and Discordant Cohort