Evaluation of MIB-1 and p53 overexpression as risk factors in large cell non-Hodgkin lymphoma in adults.
BACKGROUND
Improvement of current results of therapy for large cell non-Hodgkin lymphoma patients can be achieved by optimization of initial treatment or application of risk-adapted therapy. The international prognostic index ( IPI), introduced to identify high-risk patients, was recently criticized because it was based on clinical risk factors only, ignoring important tumor molecular risk factors and it fails to identify a sector of high-risk patients, who ultimately relapse.


OBJECTIVE
The aim of this study is to evaluate the value of two tumor biomarkers:MIB-1 and p53 as potential risk factors in diffuse large cell lymphoma. MIB-1 measures tumor cell proliferation, whereas p53 is related to tumor progression and response to chemotherapy.


METHODS
The study was done on 69 adult patients with diffuse large cell NHL ( 58 B-phenotype and 11 T-phenotype). Clinical risk assessment was determined by the IPI and patients with a score of 3 or more were considered high-risk. Expression of MIB-1 and p53 was determined by immunohistochemistry and nuclear staining was quantitated by image analysis. Immunoexpression was considered high for MIB-1 nuclear count 50% and p53 counts 20%. Evaluation included both response to chemotherapy ( mostly CHOP), as well as 2- year overall survival analysis.


RESULTS
The IPI was the only clinical variable which had a significant impact on survival. Overexpression of both MIB-1 and p53 was associated with poor response to treatment, as well as unfavorable survival. Combined risk factor analysis revealed that only MIB-1 was an independent variable. MIB-1 could also identify some high-risk patients previously categorized in the IPI lowrisk group.


CONCLUSIONS
MIB-1 is an independent biologic risk factor for large cell NHL. In order to optimize risk assessment of these patients, it is recommended to construct a new prognostic index by adding MIB-1 overexpression to the other clinical factors of standard IPI. This may allow better identification of high-risk patients and help to guide planning of effective initial treatment. Key Words:NHL - MIB-1 - p53 - CHOP - Risk factors.
El-Bolkainy
Tarek N
TN
The Departments of Pathology1, Medical Oncology2, NCI, Cairo University, Clinical Pathology3, Faculty of Medicine,Cairo University and Epidemiology& Biostatistics4, NCI, Cairo University.
El-Bolkainy
Mohamed N
MN
Khaled
Hussein M
HM
Mokhtar
Nadia M
NM
Eissa
Saad S
SS
Gouda
Heba M
HM
El-Hattab
Omar H
OH
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53