The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival

Author:

O'Shea Derville1,O'Riain Ciarán1,Taylor Claire2,Waters Rachel3,Carlotti Emanuela1,MacDougall Finlay1,Gribben John1,Rosenwald Andreas4,Ott German45,Rimsza Lisa M.6,Smeland Erlend B.78,Johnson Nathalie9,Campo Elias10,Greiner Timothy C.11,Chan Wing C.11,Gascoyne Randy D.9,Wright George12,Staudt Louis M.13,Lister T. Andrew1,Fitzgibbon Jude1

Affiliation:

1. Centre for Medical Oncology, Barts and the London School of Medicine, London, United Kingdom;

2. Mutation Detection Facility, St James's University Hospital, Leeds, United Kingdom;

3. Centre for Statistics in Medicine, Oxford University, Oxford, United Kingdom;

4. Institute of Pathology, University of Würzburg, Würzburg, Germany;

5. Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany;

6. Department of Pathology and Arizona Cancer Center, University of Arizona, Tucson;

7. Department of Immunology, Institute for Cancer Research, Rikshospitalet University Hospital, Oslo, Norway;

8. Centre for Cancer Biomedicine, Faculty Division, Norwegian Radium Hospital, University of Oslo, Oslo, Norway;

9. Department of Pathology and Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC;

10. Hematopathology Section, Department of Pathology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain;

11. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha; and

12. Biometric Research Branch and

13. Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD

Abstract

Abstract The International Prognostic Index and the Follicular Lymphoma International Prognostic Index are widely used for the risk assessment of follicular lymphoma (FL). Although molecular studies have provided insight into the biology of FL, no molecular marker has impacted on treatment stratification. Because TP53 mutations are associated with poor prognosis in hematologic malignancies, we investigated the prognostic value of TP53 mutation at diagnosis in FL. Heterozygous TP53 mutation was detected in 12 of 185 (6%) analyzed cases. Mutation was associated with older age (P = .02) and higher International Prognostic Index score (P = .04). On multivariate analysis, TP53 mutation correlated with shorter progression-free survival (P < .001) and overall survival (P = .009). TP53 mutation was associated with low expression of the immune-response 1 gene expression signature (P = .016) and with an unfavorable gene expression-based survival predictor score (P < .001), demonstrating for the first time that molecular features of the malignant cell may correlate with the nature of the immune response in FL.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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