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.
Aref
S
S
Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egipt.
Fouda
M
M
El-Dosoky
E
E
Menessy
A
A
Mabed
M
M
Saleeb
M
M
Zalata
K
K
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