Abstract
Simple SummaryHistological transformation remains the leading cause of death in patients diagnosed with follicular lymphoma (FL). To date, no clinical nor biological biomarkers have been identified to unequivocally predict patients in high risk of transformation. In this study, we investigated the predictive value of the hyaluronic acid receptors RHAMM and CD44. Expression levels of RHAMM were higher in patients with subsequent transformation and were associated with poorer outcome.Histological transformation (HT) remains the leading cause of mortality in follicular lymphoma (FL), underlining the need to identify reliable transformation predictors. The hyaluronic acid receptors CD44 and the receptor for hyaluronan mediated motility (RHAMM, also known as HMMR and CD168), have been shown to be involved in the pathogeneses of both solid tumors and hematological malignancies. In an attempt to improve risk stratification, expression of RHAMM and CD44 were evaluated by immunohistochemistry and digital image analysis in pre-therapeutic tumor-tissue biopsies from FL patients, either without (nt-FL, n = 34), or with (st-FL, n = 31) subsequent transformation, and in paired biopsies from the transformed lymphomas (tFL, n = 31). At the time of initial diagnosis, samples from st-FL patients had a higher expression of RHAMM compared with samples from nt-FL patients (p < 0.001). RHAMM expression further increased in tFL samples following transformation (p < 0.001). Evaluation of CD44 expression showed no differences in expression comparing nt-FL, st-FL, and tFL samples. Shorter transformation-free survival was associated with high tumoral and intrafollicular RHAMM expression, as well as with low intrafollicular CD44 expression (p = 0.002, p < 0.001, and p = 0.034, respectively). Our data suggest that high tumor-tissue RHAMM expression predicts the risk of shorter transformation-free survival in FL patients already at initial diagnosis.
Highlights
Introduction conditions of the Creative CommonsFollicular lymphoma (FL) is a lymphoproliferative neoplasia arising from germinal center B cells, comprising approximately 20% of all non-Hodgkin lymphomas
The cumulative incidence of histological transformation (HT) has decreased after the introduction of CD20-targeting therapy, transformation markedly reduces the response to treatment and results in the reduction in median survival time after transformation of approximately 1–2 years [7–11]
Patients with subsequent transformation had higher risk profiles compared with nt-follicular lymphoma (FL) patients, with more advanced
Summary
Follicular lymphoma (FL) is a lymphoproliferative neoplasia arising from germinal center B cells, comprising approximately 20% of all non-Hodgkin lymphomas. FL is generally considered incurable because most patients eventually experience progression with recurrent relapses. A subset of patients experience early disease progression and treatment refractoriness [1–5]. The cumulative incidence of HT has decreased after the introduction of CD20-targeting therapy, transformation markedly reduces the response to treatment and results in the reduction in median survival time after transformation of approximately 1–2 years [7–11]. No single biological event or mechanism has been shown to account for HT; the observed clinical heterogeneity may reflect different underlying molecular mechanisms. No clinical nor biological markers have been identified as unequivocal predictors of HT [11]
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