Kronik Lenfositik Lösemi Lenfoma Olgularında P53 Ekspresyonunun ve Tp53 Mutasyon Varlığının Prognoz ile İlişkisi

Abstract

hronic lymphocytic leukemia/lymphoma (CLL) is the most common lymphoproliferative disease in adults. The aim of this study is to find out if the expression of p53 and/or p53 mutation status is related to disease prognosis. In the scope of this study, 54 biopsy specimens from 51 patients (50 of them are lymph node, others are spleen, tonsil, orbita and liver) diagnosed as CLL in Hacettepe University Department of Pathology in 2000-2013, were re-evaluated. The clinical and demographic data of patients were obtained from our patients? database. Biopsy samples were assessed semi-quantitatively for the percentage of proliferation center/total biopsy area (PM/TBA) and an immunohistochemical study was performed on representative blocks of tissues for p53 expression levels. DNA was isolated from samples with high (?%5) p53 expression and the sequence analysis was performed for exons 5, 6, 7, 8 and 9 of TP53 gene. When the patients are divided into two categories according to the RAI stages as high and low (stage 0, 1, 2 vs stage 3, 4) it was seen that patients with low RAI stage have a better prognosis than those with high stages (p=0,030). However there is no statistically significant correlation between overall survival and PM/TBA ratio, p53 expression levels, blood leukocyte, absolute lymphocyte, platelet and hemoglobin counts. P53 sequences could be obtained from 10 cases due to poor quality of DNA extracted from formalin fixed paraffin embedded samples. Among these 10 cases 2 had a GCC>GGT nucleotide change on codon 154. As a result, in this study where a limited number of cases could be assessed, no correlation could be shown between high expression levels of p53 observed with immunohistochemistry and presence of TP53 mutations. In the light of the studies emphasizing the importance of the effect of TP53 abnormalities on CLL prognosis, we foresee that TP53 mutation analysis may be a routine test with newly developed next generation sequencing techniques.