Aref S, Fouda M, El-Dosoky E, Menessy A, Mabed M, Saleeb M, Zalata K
Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egipt.
Hematology. 2003 Jun;8(3):183-90. doi: 10.1080/1024533031000090829.
The product of proto-oncogene c-Myc is a potent activator of cell proliferation. The prognostic importance of the over expression of c-Myc and its transcriptional target Cdc25A in non-Hodgkin lymphoma (NHL) patients remains to be elucidated. To determine the role and the prognostic relevance of c-Myc and Cdc25A over expression in this group, we analyzed the expression of c-Myc oncoprotein by immunohistochemistry and Cdc25A mRNA by reverse-transcription polymerase chain reaction (RT-PCR) in the biopsied lymph nodes of 59 NHL patients. Over expression of c-Myc oncoprotein (P62) was observed in 32 out of 59 samples (54.2%) and Cdc25A in 36 out of 59 (60.1%). The percentage of c-Myc oncoprotein and Cdc25A mRNA over expression was significantly increased from low grade (4/12=25%, 4/16=25%) through intermediate grade (9/20=45%, 10/20=50%) to high grade lymphoma (19/23=82.6%, 22/23=95.6%) respectively (P=0.001 for both). The proportion of patients with positive c-Myc and Cdc25A over expression was significantly higher among patients with elevated serum lactic dehydrogenase (sLDH), and serum beta 2 microglobulin compared to those with normal levels (P<0.05, <0.01, respectively). Moreover, 80 and 90% of NHL patients with bone marrow infiltration at diagnosis had c-Myc and Cdc25A over expression, respectively. On the other hand, positive c-Myc, and Cdc25A over expression were not significantly related to the grade of international prognostic index, or the presence of B symptoms or to histopathological type. The expression of c-Myc and Cdc25A was significantly elevated in those who died when compared to survivors (P<0.001 for both). Moreover, positive c-Myc and Cdc25A over expression was associated with shortened overall survival.
over expression of c-Myc and Cdc25A may be poor prognostic factor in NHL and associated with poor outcome. Assessments of c-Myc and Cdc25A expression in NHL at diagnosis are likely to be helpful in predicting patient outcome and selecting optimal therapeutic regimen.
原癌基因c-Myc的产物是细胞增殖的有效激活剂。c-Myc及其转录靶点Cdc25A在非霍奇金淋巴瘤(NHL)患者中过表达的预后重要性仍有待阐明。为了确定c-Myc和Cdc25A过表达在该组中的作用及预后相关性,我们通过免疫组织化学分析了59例NHL患者活检淋巴结中c-Myc癌蛋白的表达,并通过逆转录聚合酶链反应(RT-PCR)分析了Cdc25A mRNA的表达。59个样本中有32个(54.2%)观察到c-Myc癌蛋白(P62)过表达,59个中有36个(60.1%)观察到Cdc25A过表达。c-Myc癌蛋白和Cdc25A mRNA过表达的百分比分别从低级别淋巴瘤(4/12 = 25%,4/16 = 25%)、中级别淋巴瘤(9/20 = 45%,10/20 = 50%)到高级别淋巴瘤(19/23 = 82.6%,22/23 = 95.6%)显著增加(两者P均 = 0.001)。血清乳酸脱氢酶(sLDH)和血清β2微球蛋白升高的患者中,c-Myc和Cdc25A过表达阳性的患者比例显著高于水平正常的患者(分别为P < 0.05,< 0.01)。此外,诊断时骨髓浸润的NHL患者中,分别有80%和90%的患者c-Myc和Cdc25A过表达。另一方面,c-Myc和Cdc25A过表达阳性与国际预后指数分级、B症状的存在或组织病理学类型无显著相关性。与幸存者相比,死亡患者中c-Myc和Cdc25A的表达显著升高(两者P < 0.001)。此外,c-Myc和Cdc25A过表达阳性与总生存期缩短相关。
c-Myc和Cdc25A过表达可能是NHL的不良预后因素,并与不良结局相关。在NHL诊断时评估c-Myc和Cdc25A的表达可能有助于预测患者预后并选择最佳治疗方案。