To address this issue, formalin-fixed, paraffin-embedded tissue specimens representing 47 cases of NHL were obtained from the Departments of Pathology, Assuit University Hospitals. Immunohistochemical evaluation was carried out using immunoperoxidase staining methods and mouse monoclonal antibodies (clones 124, IgG1, kappa, and DO1 for Bcl-2 and p53, respectively; DAKO Corporation, Denmark). Additional sections, running in parallel but with omission of the primary antibodies, served as the negative controls. The positive controls consisted of lymph nodes with reactive hyperplasia (for bcl-2) and squamous cell carcinoma (for p53). The percentages of positive cells (PP%) of p53 (nuclear staining) and bcl-2 (cytoplasmic staining) protein expression, apoptotic (AI) and mitotic (MI) indices were evaluated [4].
Our results revealed gradual down-regulation of bcl-2 staining values with the transition from low to intermediate- to high-grade NHL (87.7 ± 4.9 > 72.60 ± 3.4 > 66.1 ± 3.3, P=0.041). This down-regulation may be due to (i) up-regulation of bcl-2 antagonists, i.e. p53 protein, (ii) another prosurvival molecule rather than Bcl-2 protein takes over its role and (iii) epigenetic mechanisms such as Bcl-2 promoter hypermethylation [5]. Alternatively, the p53 staining values showed gradual up-regulation with the transition from low to intermediate to-high-grade NHL (6.50 ± 3.1 < 12.8 ± 4.8 < 18.5 ± 5.1, P=0.023). This up-regulation may be due to the presence of p53 gene mutations that stabilize the mutant p53 protein, and increase its half-life leading to its accumulation in the cells [3
]. The negative correlation between bcl-2 and p53 protein expression in NHL (r=0.221, P=0.165) suggests that the former is negatively regulated by the latter (Figure 1).
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In summary, our study proposes that altered bcl-2 and p53 protein expression is involved in lymphomagenesis.
Pathology Departments, School of Medicine, and South Egypt Cancer Institute, Assuit University, Assuit, Egypt
* Email: mrh17{at}swissinfo.org
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