INCREASED CCND1 FISH SIGNALS ARE ASSOCIATED WITH WORSE PROGNOSIS IN MANTLE CELL LYMPHOMA

Introduction: Follicular lymphoma (FL) is the second most frequent neoplasm in B cells. Epstein Barr Virus (EBV) causes a latent infection in B-lymphocytes with transformation capacity; however in FL there is just one previous publication that documented 2.6% of prevalence and there are no studies in Latin America. Other factors related to worse overall survival (OS) are P53 mutations and the transcription factor FOXP1, who is down-regulated in presence of EZH2 mutations. In search of prognostic biomarkers for LF, and in the absence of molecular tests for TP53 and EZH2, we wanted to determine the prognostic value of FOXP1 and P53, as well as the association between EBV and LF in a Mexican population. Methods: We conducted an observational, descriptive, analytical and retrospective study including cases with lymph node diagnosis of LF. We obtained clinical data from the electronic records and reviewed the slides selecting the representative area of the neoplasia for tissue microarrays (TMA), in situ hybridization (EBER-ISH) and immunohistochemical markers. The statistical analysis was performed using Kaplan-Meier curves, Log-rank test and Cox regression using IBM SPSS version 25. Results: We analyzed 228 patients, with a median OS of 13.4 years; 16% of the cases were EBV+. We found association in EBV+ patients to low hemoglobin ≤12mg/L (p = 0.014) and albumin ≤4g / dL (p = 0.009) levels. EBV+ patients had shorter OS than the EBV(7 vs. 13 years, p = 0.029). EBV+ combinations with Ki67 ≥ 40% and histological grade 3 were associated with OS of 3.6 and 3.2 years respectively (p = 0.052, p = 0.017). Concurrent expression of EBV+, FOXP1 ≥ 10% and Ki67 ≥ 40% reduces OS to 2.9 years (p = 0.004). P53 expression ≥ 1% was positive in 100% of EBV+ cases (p = 0.021) while p53 ≥ 20% was positive in 31% of them (p = 0.067). FOXP1 expression ≥ 85% was negatively associated with OS (p = 0.010) and relapse-free survival (RFS) (p = 0.051), as was p53 ≥ 10% (p = 0.035). FOXP1 ≥ 10% concurrent with EBV+ decreases OS to 6.7 years (p = 0.014). Multivariate analyses for OS confirmed FOXP1 ≥ 85% as independent prognostic factor. Conclusions: The LF/EBV+ association has a high prevalence in Mexico with a significant prognostic value for OS. FOXP1 expression ≥ 85%, but not at 10% was an independent factor of poor prognosis. P53 had an impact on OS at a cut-off value of 10%, independently of EBV status. Those LF/EBV+ patients with concurrent Ki67 expression (≥ 40%) and histological grade 3 exhibited worse prognosis. We consider of particular importance to identify relevant prognostic factors in the Mexican population. These biomarkers should be both reproducible and accessible to our diagnostic capabilities allowing the development of better therapeutic strategies for high-risk EBV+ LF cases.