Enemark Marie Beck, Hybel Trine Engelbrecht, Madsen Charlotte, Lauridsen Kristina Lystlund, Honoré Bent, Plesner Trine Lindhardt, Hamilton-Dutoit Stephen, d'Amore Francesco, Ludvigsen Maja
Department of Hematology, Aarhus University Hospital, 8200 Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark.
Cancers (Basel). 2022 Mar 4;14(5):1316. doi: 10.3390/cancers14051316.
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.
组织学转化（HT）仍然是滤泡性淋巴瘤（FL）死亡的主要原因，这凸显了识别可靠的转化预测指标的必要性。透明质酸受体CD44以及透明质酸介导的运动受体（RHAMM，也称为HMMR和CD168）已被证明参与实体瘤和血液系统恶性肿瘤的发病机制。为了改善风险分层，通过免疫组织化学和数字图像分析评估了FL患者治疗前肿瘤组织活检中RHAMM和CD44的表达，这些患者有的未发生（nt-FL，n = 34），有的随后发生了转化（st-FL，n = 31），还评估了转化淋巴瘤（tFL，n = 31）的配对活检样本。在初始诊断时，st-FL患者的样本中RHAMM的表达高于nt-FL患者的样本（p < 0.001）。转化后tFL样本中RHAMM的表达进一步增加（p < 0.001）。CD44表达评估显示，nt-FL、st-FL和tFL样本之间的表达没有差异。无转化生存期较短与肿瘤内和滤泡内RHAMM高表达以及滤泡内CD44低表达相关（分别为p = 0.002、p < 0.001和p = 0.034）。我们的数据表明，肿瘤组织中RHAMM高表达在初始诊断时就可预测FL患者无转化生存期较短的风险。
