Increased Expression Levels Of SOX11 Correlates To Overall Survival and Adds Prognostic Value To The MIPI and MIPI-B Index In a Homogenously Treated Cohort
Authors: Nordström Lena , Kuci Venera , Sernbo Sandra , Groenbaek Kirsten , Kolstad Arne , Räty Riika , Karjalainen Marja-Liisa , Geisler Christian , Ralfkiaer Elisabeth , Sundström Christer , Laurell Anna , Delabie Jan , Ehinger Mats , Jerkeman Mats , Ek Sara 
Published: October 2019

Abstract

Introduction
Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, previously correlated to a short survival of 3-5 years. Modern clinical protocols, combining immunochemotherapy, high-dose therapy and autologous stem cell transplantation (ASCT) have remarkably improved survival reaching a median survival of more than 10 years. To enable patient stratification, a MCL international prognostic index (MIPI) has been created similar to the international prognostic index (IPI) and follicular lymphoma international prognostic index (FLIPI). However, MIPI alone, or in combination with Ki-67 (MIPI-B), has shown limited use in guiding treatment decisions by poorly separating low and intermediate risk group patients treated with novel clinical protocols.
The transcription factor SOX11 has during recent years been shown to be an important diagnostic, prognostic and functional antigen in MCL. We have recently developed a monoclonal antibody to target SOX11 in clinical applications such as IHC and FACS. Using this antibody with improved specificity, we investigated the prognostic use of SOX11 in the homogenously treated Nordic MCL2 and MCL3 cohort. Additionally, we investigated the prognostic value by combining SOX11 and MIPI/MIPI-B.

Methods
The Nordic MCL2 (n=58) and MCL3 (n=69) patient cohort, treated with first line intensive immunochemotherapy, followed by high-dose chemotherapy and ASCT as well as addition of ibritumomab radioimmunotherapy for MCL3 patients, was stained for SOX11 expression in relation to clinicopathological and biological parameters such as Ki-67, P53 and Cyclin D1.

Results
In total, 95 % of the Nordic MCL2/3 cohort expressed SOX11, similar to previous studies. The nuclear SOX11 stainings were classified based on both intensity and frequency; negative, weak, strong ≤ 30 % and strong > 30 %. We show that high protein levels of SOX11 (strong > 30 %) correlate to an increased survival among MCL2/3 patients (p=0.02). A positive correlation between SOX11 and Cyclin D1 (p=0.006) was identified while both P53 (p<0.001) and Ki-67 (p=0.008) showed negative correlations. More importantly, we could show that SOX11 adds prognostic value to MIPI by separating the low/intermediate MCL2/3 patient cohort into two groups with a significant difference (p=0.007) in overall survival (OS). Additionally, combining SOX11 and MIPI-B identified a large group of low risk patients with more than 10 years OS.

Conclusions
We show that the expression level of SOX11 correlates to improved OS in the Nordic MCL2/3 cohort, and this is the first time SOX11 has been correlated to survival in a homogenously treated cohort. Furthermore, the use of SOX11 can separate MIPI low/intermediate patients into two groups with significant difference in OS. SOX11 in combination with MIPI-B defines both a large group of patients with great outcome that benefit from the current treatment and a distinct reduced high risk group of patients with a short survival that potentially should receive alternative treatment. Thus, combining SOX11 status and the MIPI/MIPI-B can be used to stratify patients for treatment selection.

Disclosures:
No relevant conflicts of interest to declare.