[Value of protein 53 expression in lymphoma. Its correlation with genetic mutations].

Purpose: p53 is a tumour suppressor gene encoding a nuclear phosphoprotein that plays an important role in the control of normal cell proliferation. We have tried to establish the value of expression of the p53 protein in malignant lymphomas and its correlation with the presence of structural gene abnormalities.

Material And Methods: 230 cases of lymphomas (11 Hodgkin's disease and 219 non-Hodgkin's) were studied by immunohistochemistry using an anti-p53 monoclonal antibody (DO-7, DAKO). Sections were heated by pressure cooker in 0.01 M sodium citrate buffer pH 6 as a method for antigen unmasking. The quantification of levels of nuclear p53 protein were measured with an Image Analyzer (CAS-200, Becton-Dickinson S.A.). We have also searched for mutations in a series of 94 lymphomas using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis in exons 5 to 9 of the p53 gene and the sample showing abnormal pattern were sequenced.

Results: p53 immunoreactivity has been detected in 82.6% of cases. The percentage of positive cells varies in a wide range which was divided into 0% (17.39%), less than 5% (57.39%), between 5-10% (13.91%) and more than 10% (11.30%). In all lymphoma subtypes, we have found the majority of cases show levels less than 10% and few more than 10%. We found abnormal bands in 9 of 94 lymphomas with different diagnosis (1 ALCL, 1 T-LNH, 2 B-LNH, 2 centroblastic, 1 lymphoblastic and 2 MALT). Two cases resulted to be a silent base change which not alter the function of the p53 protein and represent a common polymorphism. Seven cases showed single base pair missense mutations in all of them. Mutations in codons 179, 248 and 273 correspond to some of the typical hotspots described in p53 gene.

Conclusions: p53 expression, is a frequent finding in malignant lymphomas, is variable and relates to histological subtype. The results suggest that positive immunocytochemistry cannot be used to determine which tumours have mutations of p53 because the existence of cases with discrepancies between overexpression of the protein and presence of mutations.