TBLR1 and CREBBP as potential novel prognostic immunohistochemical biomarkers in diffuse large B-cell lymphoma

Abstract

Recent studies have identified prognostic mutational clusters for diffuse large B-cell lymphoma (DLBCL) patients, both within and outside the original cell-of-origin (COO) classification. For many of these mutations, there is limited information regarding the corresponding protein expression. With the aim to determine the relationship of protein expression and intensity to COO and prognosis, we used digital image analysis to quantitate immunohistochemical staining of CREBBP, IRF8, EZH2, and TBLR1 in 209 DLBCL patients. We found that patients with strong nuclear expression of TBLR1 had inferior progression-free survival (PFS) and overall survival (OS) in univariable analysis and inferior PFS in multivariable analysis. Patients with higher proportion of intermediate to strong nuclear CREBBP expression had a worse PFS and OS in univariable analysis. CREBBP was expressed with stronger intensity in non-GCB patients and the prognostic impact was restricted to this subgroup. These findings suggest that high nuclear protein expression of TBLR1 and CREBBP is negatively associated with prognosis in DLBCL.

Keywords:

• DLBCL
• CREBBP
• TBLR1
• prognosis
• digital image analysis

Acknowledgements

The authors thank Shahin De Lara, Department of Pathology, Sahlgrenska University Hospital, for the performance of TMA sectioning, optimizing and performance of IHC stainings. Erik Holmberg for expert statistical assistance. Ylva Magnusson and Göran Landberg, Department of Pathology and Genetics, Sahlgrenska Academy, Gothenburg University and Kristina Lövgren, Department of Oncology and Pathology, Lund University Cancer Center, Lund University, for the production of TMA blocks. We thank Edanz Group for editing a draft of this manuscript.

Disclosure statement

P.O.A. joined the speakers’ bureau of Roche, Gilead, and Janssen and has been a consultant for Abbvie, Gilead, Janssen, and Roche. H.N.E. joined the speakers’ bureau of Roche and Janssen and has been a consultant for Roche. The other authors declare no conflicts of interest regarding the publication of this paper.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by funding from Borås Cancer Foundation, from the Swedish State under the Agreement between the Swedish Government and the Country Councils; the ALF-agreement [79606], Lions Cancerfond Väst and the Swedish Cancer Society.