Abstract
Follicular lymphoma (FL) is an indolent neoplasia comprising approximately 20% of lymphomas. FL is generally considered incurable, with a median survival exceeding 10 years. A subset of FL patients experiences histological transformation (HT) to a more aggressive lymphoma, resulting in markedly poorer clinical outcome, with a reduced median survival after transformation of 1–2 years. Early, reliable prediction of HT would be valuable in the clinical setting, allowing pre-emptive therapeutic intervention. We previously used proteomics to identify the glycolytic enzymes fructose-bisphosphate aldolase A (aldolase A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as candidate predictors of FL transformation. Now, we use immunohistochemistry to evaluate expression of these enzymes in paired primary FLs from patients with (n = 41) or without subsequent HT (n = 49), to test their value as predictive biomarkers. At initial FL diagnosis, patients with subsequent HT had significantly higher expression of aldolase A and GAPDH (p<0.001 and p<0.01) compared with patients without HT. Furthermore, high expression of aldolase A and GAPDH was associated with significantly shorter transformation free survival (p = 0.018, p = 0.001). These data suggest that high expression of aldolase A and GAPDH, may indicate increased metabolic turnover, and that these enzymes may be useful biomarkers in primary FL for predicting the risk of subsequent lymphoma transformation.
Highlights
Follicular lymphoma (FL) is an indolent lymphoma derived from germinal center B cells [1]
We have examined the predictive potential of the two glycolytic enzymes by immunohistochemical evaluation of their expression in pretherapeutic tumor tissue from time of initial FL diagnosis in patients, with and without subsequent histological transformation (HT)
FL patients with subsequent transformation (s-FL, n = 49) had a more adverse risk profile compared with patients without HT, with a more advanced Ann Arbor stage, higher FLIPI score, typically with LDH-elevation, and bone marrow involvement
Summary
Follicular lymphoma (FL) is an indolent lymphoma derived from germinal center B cells [1]. It is the second most common lymphoid malignancy, accounting for some 20% of all nonHodgkin lymphomas, and is predominantly a disease of adults, the median age of patients at diagnosis being approximately 60 years [2,3]). FL is generally considered an incurable condition with a median survival time exceeding 10 years in the ‘rituximab era’ [2,4]. A portion of patients still experience early progression, treatment refractoriness and histological transformation (HT) to a more aggressive lymphoma subtype, typically diffuse large B-cell lymphoma (DLBCL). The occurrence of HT has a clear adverse impact on the patient’s prognosis, lowering the median survival after transformation being typically reduced to 1–2 years [5,6]
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