Expression Of FOXP1 And CyclinE In Primary Central Nervous System Lymphoma And Clinical Analysis

Background and objectives:Primary central nervous system lymphoma (PCNSL) is an uncommon form of non-Hodgkin's lymphoma (NHL) confined to brain, spinal cord or eye. Immunodeficiency is the main risk factor, but epidemiologic data suggest a recentdecrease in the incidence of PCNSL among immunodeficiency individuals, probably associated with the development of new active antiviral drugs. On the other hand,PCNSL incidence among immunocompetent individuals has been progressively increasing in rencent years. The pathologic, prognosis and treatment of PCNSL is different from systemic NHL. Because of the complexed clinical manifestation, the difficulties in diagnosis,the clinical outcome of PCNSL is still poor and no standard treatment is available so far.A large number of studies have consistently identified age and performance status as the main independent prognostic factors of PCNSL, while the prognostic significance of biomarkers remains unclear. Prevous reseaches mainly focused on markers related to B-cell origin and angiogenesis, under evaluation of large clinical trials. FOXP1 with a crucial role in transcription is a member of the FOXP protein family. A series of researches associated FOXP1 with DLBCL shorter survival independ--ently,and more expressed in DLBCL-ABC.CyclinE is an important regulator for transition from G1 to the S phase of the cell cycle. Recent studies have comfirmed that CyclinE is an unfavorable factor, predicting a shorter survival independently in patients with systematic diffuse large B-cell lymphoma (DLBCL).However, FOXP1 has been few investigated in PCNSL, and CyclinE have not been investigated in PCNSL.we have therefore reviewed 71 PCNSLs in immunocomptent patients, detected expression levels of the two genes by immunohistochemistry method and evaluated their prognostic significance in PCNSL, evaluate the prognostic factors and response to treatment systematically in PCNSL, as to make some help to clinical management of PCNSL in future.Materials and methods:Review clinical imformations of 71 patients with PCNSL between 2002 and 2007.A11 patients were diagnosed by pathology biopsy with no evidence of systematic involvement. Immunohistochemistry method (HRP-EnVisionTM)were performed with monoclonal antibody against FOXP1 in 51 cases of PCNSL patients and CyclinE in 50 cases of it. Clinical characters and regimens of the cases were summarized.Associations of both FOXP1 and CyclinE expressions with clinical parameters were assessed by the Fisher exact test. Survival curves were constructed using the Kaplan-Meier method. Univariate analyses of survival curves were performed using the log-rank test; Variables that considered significant prognostic factors were included in a multivariate analysis using the Cox proportional hazards regression model. The Stata 9.0 statistical software system was used for calculations.Results:FOXP1 and CyclinE expression was immunohistochemically determined in 51 and 50 previously untreated patients with PCNSL. High FOXP1 expression was observed in 35 of 51 patients (68.63%)and CyclinE staining was present in 29 of 50 cases (58%).In clinical parameters including age,ECOG performance status, multiple lesions, deep structure involved, signs of raised intracranial pressure and proliferation marker MIB1,patients with high or low FOXP1 expression did not differ signifiantly. CyclinE expression was observed the same state asFOXP1.The median follow-up of the total study population was 17 months, The estimated 2-year overall survival of all patients was 30.01%. The estimated 3-year overall survival of all patients was 23.88%. Patients with high FOXP1 expression had a shorter overall survival than those with low FOXP1 expression.Kaplan-Meier estimate of survival at 2 years was 23.33% for patients with high FOXP1 expression and 73.56% for patients with low FOXP1 expression (x2=10.14, P=0.0015); Patients with high CyclinE expression had a shorter overall survival than those with low CyclinE expression.Kaplan-Meier estimate of survival at 2 years was 17.56% for patients with high CyclinE expression and 69.76% for patients with low CyclinE expression (X2=9.82, P=0.0017); In the multivariate analysis that include, age, FOXP1, CyclinE, the interval between occurrence and diagnosis of the disease, hb level, the hazard odds ratio for death was 2.44 for high CyclinE expression and 8.05 for low hb level. Thus, CyclinE expression and hb level were the independent factor predicting a shorter overall survival. the hazard odds ratio for death was 2.77 for high FOXP1 expression and 1.88 for the interval between occurrence and diagnosis of the disease. FOXP1 expression and the interval between occurrence and diagnosis of the disease were the important factor predicting a shorter overall survival.Conclusion:High FOXP1 expresses more frequently in PCNSL than in systematic DLBCL,that is to say,PCNSL was most probably activated B-cell.High CyclinE expression and low hb level is an independent predictive and prognostic factor associated with poor clinical outcome in patients with PCNSL. High CyclinE expression and low hb level might become a clinically useful marker for the selection of patients for specific treatments. FOXP1 expression were the important factor predicting a shorter overall survival.