Sun R X, Coste J, Segara C, Rousset T, Fabbro M, Rème T, Legouffe E, Klein B, Rossi J F
INSERM, Montpellier, France.
Clin Lab Haematol. 1998 Apr;20(2):87-94. doi: 10.1046/j.1365-2257.1998.00090.x.
Non-Hodgkin's lymphomas (NHL) are B-cell malignancies which generally present molecular abnormalities, such as bcl-2 translocation t(14; 18) predominantly in the follicular subgroup. Other molecular events have been described in NHL, including p53 gene mutation and overexpression of one chemoresistance mechanism, the multidrug resistance system, P-glycoprotein (MDR 1/P-gp). In this study, we analysed samples from 44 NHL patients with the presence of the bcl-2 major breakpoint region (MBR) rearrangement in 29 and without in 15. Immunochemical analysis revealed that 39 samples were positive for bcl-2 protein expression in tumoral cells (88.6%). Seventeen (38.6%) patients expressed P-gp and 9 (20.5%) expressed p53 proteins. Eleven patients expressed both bcl-2 and P-gp proteins, four expressed bcl-2 and p53 proteins whereas four expressed bcl-2, p53 and P-gp proteins. Our results confirm the importance of p53 expression as a key prognostic factor, and no objective response (OR) was found in patients with p53 positivity. MBR rearrangement was not associated with poor response to chemotherapy (62.1% OR in MBR positive patients v. 60% OR in MBR negative patients). The clinical impact of P-gp cannot be identified because no relationship was observed between P-gp expression and prognosis (58.8% OR in P-gp positive patients v. 63% OR in P-gp negative patients).
非霍奇金淋巴瘤(NHL)是B细胞恶性肿瘤,通常存在分子异常,例如bcl-2易位t(14; 18)主要见于滤泡亚组。NHL中还描述了其他分子事件,包括p53基因突变和一种化疗耐药机制——多药耐药系统P-糖蛋白(MDR 1/P-gp)的过表达。在本研究中,我们分析了44例NHL患者的样本,其中29例存在bcl-2主要断裂点区域(MBR)重排,15例不存在。免疫化学分析显示,39个样本的肿瘤细胞中bcl-2蛋白表达呈阳性(88.6%)。17例(38.6%)患者表达P-gp,9例(20.5%)表达p53蛋白。11例患者同时表达bcl-2和P-gp蛋白,4例表达bcl-2和p53蛋白,4例表达bcl-2、p53和P-gp蛋白。我们的结果证实了p53表达作为关键预后因素的重要性,p53阳性患者未发现客观缓解(OR)。MBR重排与化疗反应不佳无关(MBR阳性患者的OR为62.1%,MBR阴性患者为60%)。由于未观察到P-gp表达与预后之间的关系(P-gp阳性患者的OR为58.8%,P-gp阴性患者为63%),因此无法确定P-gp的临床影响。