Correlations between p16 Protein Expression and Genomic Profile in Mantle Cell Lymphoma and Impact on Survival, a Lyma-Genomic Project Conducted on Behalf of the Lysa Group

Abstract Introduction Mantle cell lymphoma (MCL) is a heterogeneous disease with a complex genetic landscape. Among genetic anomalies, alterations of several tumor suppressor genes are prognostic markers. The p16INK4A protein, encoded by CDKN2A, is known to bind and inactivate the cyclin-dependent kinase CDK4/6, blocking the phosphorylation of the retinoblastoma protein Rb and inducing cell cycle arrest. The p16INK4A and p53 overexpression are associated with poor prognosis (D. Canioni et al. ASH 2017). Here we compared the expression levels of p16INK4A and p53 in immunohistochemistry (IHC) with the profile (copy number alterations, CNAs) of the genes encoding these proteins, on diagnosis MCL lymph nodes. Results were correlated with patients' outcome in order to identify prognostic biomarkers in MCL. Methods All samples (n=86) used in the present work were collected from untreated MCL patients enrolled in the LyMa trial (S. Le Gouill et al. NEJM 2017). IHC was performed for p16INK4A and p53 protein expression assessment on formalin fixed paraffin embedded diagnostic Tissue Micro Arrays. Cut-offs for over expression of p16INK4A and p53 proteins were 10% and 30% respectively (D. Canioni et al. ASH 2016). A pan-genomic copy number analysis was performed with the Oncoscan® SNP-array on DNA extracted from the same samples. Data were compared using chi² tests. Progression free survival (PFS) and overall survival (OS) were studied by log rank test and Kaplan Meier representation. Results Patients characteristics (n=86) were similar to the whole LyMa trial population (n= 299) regarding age, gender, Ann Arbor stage and blastoid morphology. Overexpression of p16INK4A was observed in 11% of the patients and was not associated with any deletion of CDKN2A. There was a significant association between p16INK4A protein overexpression and TP53 mono-allelic deletion (38% vs 7%; p Regarding patients' outcome, early relapse or progression ( Conclusion This work shows that p16INK4A protein expression is correlated with TP53 deletion and BCL6 gain. The p16INK4A overexpression or CDKN2A double deletion could be used as prognostic biomarkers at diagnosis to predict poor response in first line treatment. Download : Download high-res image (72KB) Download : Download full-size image Disclosures Hermine: Hybrigenics: Research Funding; Erythec: Research Funding; Novartis: Research Funding; Celgene Corporation: Research Funding; AB Science: Consultancy, Equity Ownership, Honoraria, Research Funding.