SOX11 Expression Versus Indolent Clinical Course in Mantle Cell Lymphomas in a Population-Based Cohort From the Stockholm Region – SOX11 Negative Tumors Are Mostly p53 Positive, Contributing to Shorter Overall Survival,
Authors: Sander Birgitta , Klimkowska Monika , Nygren Lina , Baumgartner Stefanie , Christensson Birger , Kimby Eva 
Published: October 2019

Abstract
Abstract 3651

Introduction:
Mantle cell lymphoma (MCL) constitutes 3–10% of non-Hodgkin lymphomas and has a median survival of 3–5 years. A small number of patients are characterized by a clinically indolent disease and may not require treatment for several years. However, these are difficult to identify at the time of diagnosis due to lack of reliable predictive markers. Recently, the nuclear expression of the transcription factor SOX11 has been suggested to be of prognostic value in MCL.

Materials and Methods:
All 186 patients diagnosed with MCL in the Stockholm region between January 1998 and June 2010 were included. Diagnosis was according to the WHO criteria and all cases were cyclin D1 positive by IHC and/or for t(11;14) by FISH. Clinical data from patient files, diagnostic biopsies and flow cytometry data were reviewed. Patients not requiring treatment within the first two years after diagnosis were retrospectively defined as indolent disease.
Patients were further categorized in nuclear SOX11 negative (n=13) and nuclear SOX11 positive (n=160) cases and in cases with indolent (n=17) versus non-indolent disease course (n=169). The following variables were evaluated at the time of diagnosis: age, sex, Ann Arbor stage, ECOG, B-symptoms, Hb, LDH, albumin, lymphocytosis, leukocytosis, splenomegaly, nodal and bone marrow involvement, MIPI, indolent disease, blastoid morphology, expression of CD23, light chain, Ki 67, SOX11 and p53. Overall survival was analyzed, excluding patients receiving ASCT (n=37). Baumgartner, S. et al presents further data on the entire cohort in the accompanying abstract.

Results:
The following variables were significantly more common in SOX11 negative cases (Table 1): Lymphocytosis (p=0,045), high LDH (p=0,029) and p53 positivity (p<0,000). MIPI high risk was more frequent among SOX11 negative patients but did not reach statistical difference. There were no statistically significant differences in the frequency of splenomegaly or indolent disease among SOX11 negative and positive cases. Median overall survival time was 36,7 months in the whole cohort; 16,5 months in patients with SOX11 negative tumors and 39,3 months in patients with SOX11 positive tumors (p=0,015), excluding 37 patients (1 SOX11 negative, 38 SOX11 positive) receiving ASCT as part of first-line therapy. Patients with an indolent clinical course had significantly less often B symptoms (p=0,002), nodal presentation (p=0,019) and elevated LDH (p=0,040) than patients with a non-indolent disease, while none of the other factors analyzed reached statistical significance. Median overall survival time of patients with indolent disease was not reached (median follow-up time 41,7 months). 15/17 of the MCL cases with indolent clinical course expressed SOX11.

Conclusions:
In a population-based cohort of 186 cyclin D1 positive MCL, 8% lacked expression of nuclear SOX11 at diagnosis. There was no enrichment of patients with an indolent disease among SOX11 negative MCL. Instead patients with SOX11 negative MCL had a higher frequency of lymphocytosis and elevated LDH at diagnosis and a shorter overall survival. MCL lacking nuclear SOX11 expression at diagnosis were more frequently p53 positive which may contribute to shorter survival in the SOX11 negative MCL subset.

Disclosures:
No relevant conflicts of interest to declare.