Prognostic Role of CDKN2A Deletion and p53 Expression and Association With MIPIb in Mantle Cell Lymphoma

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2023-08, Vol.23 (8), p.599-605
• Main Authors: Gaudio, Francesco, Dicataldo, Michele, Di Giovanni, Fabrizia, Cazzato, Gerardo, d'Amati, Antonio, Perrone, Tommasina, Masciopinto, Pierluigi, Laddaga, Filomena Emanuela, Musto, Pellegrino, Maiorano, Eugenio, Ingravallo, Giuseppe
• Format: Article
• Language: English
• Subjects: Immunohistochemistry; Lymphoproliferative syndromes; Molecular analysis; Prognostic factors; Target therapies
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2023.04.004

Mantle cell lymphoma (MCL) is a rare type of lymphoma, which despite improvements in therapies in recent decades, remains an incurable disease. There is currently no reliable marker of chemoresistance available. In this study, we investigated the prognostic role of MIPIb and the association with biological markers including SOX11, p53 expression, Ki-67, and CDKN2A. This retrospective study was focused on 23 patients with newly diagnosed classical MCL, treated at the University Hospital of Bari (Italy) between January 2006 and June 2019. We identified a MIPIb value ≥ 5.4440 as a prognostic parameter that correlates with p53 expression and CDKN2A deletion. We also observed that patients with p53 overexpression had a significantly higher MIPIb (5.52 ± 0.53) which in 80% of patients had a value higher than 5.4440. On the other hand, CDKN2A deletion was found more frequently (75%) associated with MIPIb ≥5.4440. Only the CDKN2A deletion was associated with a higher proliferation index, with 66.7% of samples having Ki67 ≥30%. From the survival analysis we found that patients with p53 overexpression and CDKN2A deletion have a significantly worse prognosis with a median overall survival of 50 (P = .012) and 52 months (P = .018), respectively. p53 expression and CDKN2A deletion represent a reliable pretreatment prognostic factor that identifies patients who do not benefit from currently used immunochemotherapy-based therapies and who are candidates for diversified treatments with the aim of improving prognosis. The MIPIb represents a prognostic index that correlates well with these biological alterations and can be used in clinical practice as their surrogate. In this study, we investigated the prognostic role of MIPIb and the association with biological markers including SOX11, TP53, Ki-67 and CDKN2A.This retrospective study was focused on 23 patients with newly diagnosed classical MCL, treated at the University Hospital of Bari (Italy) between January 2006 and June 2019. We identified a MIPIb value ≥ 5.4440 as a prognostic parameter that correlates with TP53 mutation and CDKN2A deletion. From the survival analysis we found that patients with TP53 overexpression and CDKN2A deletion have a significantly worse prognosis with a median overall survival of 50 (P = .012) and 52 months (P = .018), respectively. In conclusion TP53 mutant and CDKN2A deletion represent a reliable pretreatment prognostic factor that identifies patients who do not benefit from currently used i