CD72, CD44 and MIB1 expression as indicators of recurrence free survival in Follicular Lymphoma

Introduction. Follicular lymphoma (FL) is the second most common type of B-cell non-Hodgkin's lymphoma in Western countries. It is characterized by a wide heterogeneity in onset, histopathology and disease course. According to the ESMO guidelines, treatment decisions range from watch-and-wait to immunochemotherapy (ICHT). The heterogeneity of FL is highlighted by the difficulty of identifying clinical and biological parameters that can predict clinical outcome and treatment efficacy. The diagnosis of FL is based on the characteristic cytomorphology, immunophenotype (CD10, Bcl2, Bcl6) and detection of t(14;18). Although flow cytometric immunophenotyping is rather rarely used for the characterization of lymphomas, in a previous study we had shown that Artificial Intelligence models, applied to cytometric data analysis, allow to obtain a classification of different types of lymphoma. In this study, we evaluated in a homogeneous group of lymphoma patients whether one or more immunophenotypic markers may correlate with clinical behavior. Methods. We selected 53 FLs treated with ICHT (R-CHOP or R-Bendamustin) and for whom a follow-up of more than 24 months was available. All cases were extensively characterized for immunophenotype by multiparametric flow cytometry. Results. The relapse free survival analysis shows that, in addition to the Follicular Lymphoma International Prognostic Index (FLIPI), which was found to be significantly correlated with time to post-therapy relapse, the markers correlating with relapse were MIB1>16% (p<0.03), CD44>76% (p<0.02) and CD72>67% (p<0.008) (Wilcoxon test). Among these 3 markers, the most powerful in predicting recurrence after therapy was CD72, which also positively correlates with FLIPI in multivariate analysis (p<0.05). Discussion. This study suggests that in FL some phenotypic markers correlate with clinical course, particularly with the likelihood of posttherapy recurrence. An increased proliferative index (MIB1), which is associated with a higher histological grade, may also correlate with an increased tendency for recurrence. CD44, a cell surface adhesion receptor, is widely expressed on normal and tumor cells, and its interaction with the extracellular matrix promotes the migration and invasion processes involved in metastases. The role of CD72 seems to be more intriguing. CD72 is considered a positive regulator of B lymphocyte functions in patients with autoimmune diseases. Therefore, this molecule, when expressed at high levels in FL, could allow for increased proliferative activity or confer an advantage in terms of resistance to ICHT agents.