Abstract

Introduction: Follicular lymphomas (FL) are indolent lymphomas without definitive criteria predicting their outcome. Previous immunohistochemical (IHC) studies showed controversial data about the prognostic value of IHC markers in FL. In order to clarify this issue, we evaluated p53 and Myc protein expression, 2 markers related to cancer cells and usually considered as correlated with a more aggressive behavior in many tumors including lymphomas. We used a large series of FL samples from rituximab-treated patients enrolled in the randomized PRIMA trial.

Methods: Immunohistochemistry using p53 and Myc antibodies was performed on formalin fixed parafin embedded diagnostic tissue micro arrays (TMA) of FL samples of 253 patients of the PRIMA trial. The IHC results were quantified by a semi-quantitative method using the percentage of cells stained on each TMA spot. The results were statistically compared with other clinico-biological parameters. For the 2 variables, different cut-offs were studied on progression free survival (PFS) and overall survival (OS).

Results: As to p53 protein expression, a cut-off >20% increased significantly the risk of poor PFS (HR=1.67 [1.14-2.45], p=0.008) but was not significant for OS. As to Myc protein expression, a cut-off ≥ 10% was close to be significant (p=0.056) of poor PFS but was not significant for the OS. In a multivariate analysis, only p53 remained significant (HR=1.53 [1.002-2.34], p=0.048) for poor PFS. There was no correlation between the level of p53 and Myc protein expression and the histological grade in our series. When the interaction between the two markers was compared, it was not significantly correlated.

Conclusion: These results suggest that IHC p53 protein expression in this series of 253 patients has a significant prognostic value in FL patients. More than 20% p53 positive cells indicated a worse PFS , but was not significantly associated with a worse OS. It could be then recommended to incorporate p53 IHC in routine diagnostic practice. These results are currently under validation on an independent series of FL patients

Disclosures

Feugier: Roche: Consultancy, Honoraria, Research Funding. Morschhauser: Gilead: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Servier: Consultancy. Salles: MSD: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Author notes

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Asterisk with author names denotes non-ASH members.