c-Myc oncogene and Cdc25A cell activating phosphatase expression in non-Hodgkin's lymphoma.
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.


CONCLUSIONS
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.
Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egipt.
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Aref
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Fouda
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El-Dosoky
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Menessy
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Mabed
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Saleeb
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Zalata
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D015993:Life Tables; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis* / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D001613:beta 2-Microglobulin / Q000032:analysis; D020687:cdc25 Phosphatases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics
C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D001613:beta 2-Microglobulin; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases