The Proportion of Tumor Cells Expressing SOX11 Is Associated with Progression Free Survival in Mantle Cell Lymphoma.
Luis Brandi, Gene Shaw, Kreg Grindle, Songwon Seo, Brad Kahl, Catherine Leith, Ken Young, David Yang. University of Wisconsin, Madison; Marshfield Clinic
Background: Mantle cell lymphoma (MCL) is typically an aggressive B-cell lymphoma, but the clinical course for patients is highly variable. Comparative gene expression profiling of indolent and conventional MCL cases showed that SOX11 is significantly under-expressed in indolent MCL. However, validation of these findings has produced conflicting reports regarding the lack of nuclear SOX11 protein expression and its association with indolent disease.
Design: A tissue microarray comprised of triplicate 0.6mm cores from archived formalin-fixed paraffin embedded tissues of 61 MCL cases was independently assessed for nuclear SOX11 protein expression by two pathologists as a percentage of lymphocytes demonstrating nuclear staining. This value was normalized to the percentage of CyclinD1 expressing lymphocytes in each core. Gene expression was assessed by array based quantitative nuclease protection assay and normalized to two housekeeping genes.
Results: Correlation of normalized SOX11 protein expression by two pathologists demonstrated excellent inter-rater agreement (intra-class correlation coefficient = 0.9). Cases with a higher proportion of cells demonstrating nuclear SOX11 expression were found to have a longer progression free survival (PFS) with a hazard ratio (HR) of 0.14 (95% CI, 0.05-0.4) by univariate analysis (p=0.0003). This association remained after adjusting for the MIPI score. Distribution of the cases revealed two clear groupings, a group of 9 cases with 0-30% of tumor cells expressing SOX11 (designated 'negative') and a group of 46 cases with >80% of cells positive (designated 'positive') with 4 cases 'intermediate'. Patients in the 'negative' group had significantly shorter PFS (Figure 1). These findings were supported by assessment of SOX11 gene expression, which correlated with protein expression (Pearson correlation = 0.74, p<0.001), and high levels of SOX11 gene expression was associated with longer PFS with HR=0.74 (95% CI, 0.56-0.98) by univariate analysis (p=0.04).
Conclusions: Analysis of 61 MCL cases demonstrates an association between larger numbers of cells with nuclear SOX11 expression and longer PFS.
Monday, February 28, 2011 8:15 AM
Platform Session: Section B, Monday Morning