Upper GI
Andrew Hanna, MD
Resident
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
A tissue microarray of 127 human GIST specimens (68 primary, 59 metastatic) were analyzed for IHC expression of CD3, CD4, CD8, CD68, FOXP3, and class I. Demographic, pathologic, and outcome variables were recorded. Immunohistochemical expression of all markers was correlated with demographic and pathologic variables using Student’s t-test or analysis of variance. Univariable and multivariable survival analysis was performed with Kaplan-Meier and Cox regression. Finally, two previously published bulk RNA sequencing human GIST datasets with similar variables were used to confirm our findings using survival and gene set enrichment analysis (GSEA).
Results: Class I expression correlated with very low risk tumors by Miettinen criteria, low mitotic rate, size < 5 cm, and primary (vs. metastatic) tumors (all univariate p< 0.05). Among primary GISTs, class I was the only factor predicting recurrence and overall survival on univariable Kaplan-Meier analysis (Figure) as well as multivariable Cox regression (p< 0.05). Interestingly, class I was not associated with overall survival among metastatic samples. Using a publicly available dataset combining gene expression, clinical, and survival data from 36 primary GIST patients never treated with imatinib, higher gene expression of various class I genes such as β2 microglobulin, HLA-A, HLA-B, and HLA-C was correlated with improved survival (all p< 0.05). Finally, GSEA of our gene expression dataset of 75 primary and metastatic GIST patients confirmed enrichment of class I gene sets within samples from primary GISTs with lower mitotic rate (all normalized enrichment scores >2, false discovery rate < 0.01).
Conclusions: Decreased class I expression correlates with GIST progression and metastasis. This association underscores the importance of the tumor immune environment and response in GIST clinical outcomes.