Evaluation of MIB-1 and p53 overexpression as risk factors in large cell non-hodgkin lymphoma in adults

الملخص EN

Background : Improvement of current results of ther-apy 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.

Patients and 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 quantities 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.

Over expression 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.