Immunohistochemical Classification and Prognostic Significance of Germinal Center-like and Memory Cell-like Subtypes of Follicular Lymphoma Using FOXP1, LMO2, CD22, and MUM1

Follicular lymphoma (FL) is an indolent B-cell lymphoma with considerable biological and clinical heterogeneity, highlighting the need for additional prognostic biomarkers beyond conventional clinicopathological parameters. This study aimed to evaluate the prognostic significance of an immunohistochemical classification separating FL into a germinal center-like (GC-like) phenotype, characterized by retention of germinal-center-associated features, and a memory-like (Mem-like) phenotype, reflecting a more differentiated post-germinal-center/memory B-cell state. Fifty-one patients with FL were retrospectively analyzed for clinicopathological characteristics, immunohistochemical findings, relapse, and overall survival (OS). LMO2 expression was detected in 70.6% of cases and was associated with lower mortality (19.4% vs. 60.0%, p = 0.008), lower relapse rates (8.3% vs. 33.3%, p = 0.039), and improved 5-year OS (85.3% vs. 35.0%, log-rank p = 0.003). FOXP1 positivity was observed in 41.2% of cases and was associated with higher mortality (57.1% vs. 13.3%, p = 0.002) and inferior 5-year OS (44.5% vs. 89.4%, log-rank p < 0.001). Mem-like patients had significantly poorer 5-year OS than GC-like patients (39.5% vs. 90.1%, log-rank p < 0.001). These findings suggest that LMO2 and FOXP1 expression may provide complementary prognostic information and help identify clinically distinct immunophenotypic subsets in FL.