The association of Hypoxia-Inducible Factor-2 (HIF-2) overexpression score with Germinal Center-Cell Like (GCB) and Non-Germinal Center B-Cell Like (Non-GCB) subtypes of Diffuse Large B-cell Lymphoma (DLBCL)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. It is classified into homogeneous subtypes, namely Germinal Center B-Cell Like (GCB) and Non-Germinal Center B-Cell Like (GCB), with the latter associated with worse survival outcomes. Increased expression of Hypoxia-Inducible Factor-2 alpha (HIF-2 alpha) is often observed in DLBCL and has been correlated with enhanced angiogenesis, suggesting its potential as a prognostic factor in managing DLBCL. The study evaluates the association between HIF-2 alpha overexpression and the GCB and non-GCB subtypes of DLBCL. Methods: This cross-sectional study utilized samples from DLBCL patients at Dr. Kariadi Semarang Hospital between January and December 2021. Immunohistochemistry was performed on the samples to determine the DLBCL subtypes and assess the presence of HIF-2 alpha. HIF-2 alpha was evaluated by immunohistochemistry based on its distribution and intensity. The Kruskal-Wallis test was used to find the association between HIF-2 alpha expression and the GCB and non-GCB subtypes of DLBCL. Furthermore, Spearman's rank correlation test explored the correlation between all numeric variables. Results: A total of 30 subjects were included in this study, with 7 samples of GCB subtype (23.3%) and 23 samples of non GCB subtype (76.6%). Kruskal-Wallis test showed no association between HIF-2 alpha expression and the subtypes of DLBCL (p=0.812). Spearman's rho correlation test indicated no correlation between HIF-2 alpha overexpression score with NCCN IPI score in GCB (r=0.219; p=0.637) and non-GCB (r=-0.194; p=0.386). Conclusion: There was no association between HIF-2 alpha expression and GCB and non-GCB subtypes of DLBCL. Additionally, no correlation was found between HIF-2 alpha overexpression and NCCN IPI score.