Immunocytochemical detection of bcl-2 and p53 proteins in B-chronic lymphocytic leukemia patients.
B-cell chronic lymphocytic leukemia (B-CLL) is a disease with variable course and prognosis. It may be important to predict the possible risk of disease progression in individual patients. We have investigated by immunocytochemistry the bcl-2 and p53 protein expression in 53 B-CLL patients at the time of initial diagnosis. All B-CLL cases were bcl-2 protein positive. The relatively high frequency of p53 protein immunoreactivity was observed (17 of 53 cases; 32%). The percentage of bcl-2 and p53 protein positive cells remarkably varied in individual patients. The heterogeneity in the percentage of bcl-2 as well as p53 positive cells showed to be important in the analysis of mutual relation of these proteins. Noteworthy results were obtained when the group of p53 positive B-CLL patients was analyzed according to the percentage of p53 positive cells (less than 20% and more than 20%, respectively). An inverse relationship between a higher accumulation of p53 and repressed bcl-2 expression and vice versa was observed. The male patients (female patients were not assessed because of the limited number of p53 positive cases) with less than 20% p53 immunoreactive cells revealed a high percentage of bcl-2 protein (p=0.0008). The higher incidence (over 20%) p53 positive cells correlated with lowered percentage of bcl-2 positive cells (p=0.0368). When the patients were subdivided according to p53 positivity and negativity, the majority of p53 positive cases were males (82%), with significantly higher WBC count (p=0.0362). No significant effect of higher or lower WBC counts on bcl-2 and p53 expression was observed. However, the expression of bcl-2 protein was significantly higher in female patients under 50 years (p=0.0012). Regarding the patients of age <or=50 and >50, a significant difference in WBC count was shown in males (p=0.0590). The peripheral blood lymphocytes isolated from healthy subjects used as controls, exhibited undetectable, to low proportion of bcl-2 and p53 positive cells. Comparing the percentage of bcl-2 as well as p53 positive cells in controls and those of B-CLL patients, the significant difference for both proteins was observed (p=0.0009 and p=0.0001, respectively). The results of this study indicate that the overexpression of p53 protein may contribute to the downregulation of bcl-2 in a subgroup of our B-CLL patients. Considering the small numbers of tested p53 positive cases, it would be necessary to confirm our findings in a larger cohort of patients with longer follow up. Thus it would be possible to confirm our expectation of a possible value of the simultaneous aberrant expression of bcl-2 and p53 as useful predictors of future aggressive behavior of B-CLL.
Klobusická
M
M
Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic. exonklo@savba.sk
Kusenda
J
J
Babusíková
O
O
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism*; D012737:Sex Factors; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53