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Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice
Published on: April 3, 2011
p53 in lymphomas of mucosal-associated lymphoid tissues
V Levy1, C Miller, H P Koeffler
1Department of Pathology and Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Insights
Mucosal-associated lymphoid tissue (MALT) lymphomas lack p53 mutations, unlike splenic marginal zone lymphomas. This suggests different lymphomagenesis mechanisms for MALT lymphomas, though some express low p53 protein levels.
Area of Science:
- Oncology
- Hematology
- Molecular Biology
Background:
- Mucosal-associated lymphoid tissue (MALT) lymphomas are a distinct group of B-cell lymphomas.
- Their cellular origin is debated, with potential links to marginal zone lymphocytes.
- Marginal zone lymphomas exhibit frequent p53 mutations, prompting investigation into MALT lymphomas.
Purpose of the Study:
- To investigate the presence of p53 mutations in MALT lymphomas.
- To compare p53 mutation status between MALT lymphomas and marginal zone lymphomas.
- To assess p53 gene protein product expression in MALT lymphoma tissues.
Main Methods:
- Polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) analysis of exons 4-8 of the p53 gene.
- Immunohistochemical examination for p53 protein expression.
- Analysis of MALT lymphoma specimens from gastric, parotid, and small bowel tissues.
Main Results:
- No p53 mutations were detected in any of the evaluated MALT lymphoma specimens.
- p53 gene protein product was expressed in the nuclei of neoplastic cells in 3 out of 15 MALT lymphoma cases, at low levels (<10%).
- These findings contrast with the high rate of p53 mutations observed in splenic marginal zone lymphomas.
Conclusions:
- Low-grade MALT lymphomas appear to differ from marginal zone lymphomas due to the absence of p53 point mutations.
- The distinct p53 mutation profile suggests alternative pathways in the lymphomagenesis of MALT lymphomas.
- While lacking mutations, some MALT lymphomas show low-level p53 protein expression, indicating potential roles for p53 independent of mutation.
Abstract:
Lymphomas of mucosal-associated lymphoid tissues (MALT) constitute a distinct clinicopathologic entity comprised of centrocyte-like cells with a characteristic morphologic appearance and immunophenotype. The origin of these cells is still undetermined, although evidence suggests that they might derive from marginal zone lymphocytes present in normal lymph nodes and spleens. Recently, marginal zone lymphomas have been shown to have a high rate of p53 mutation. To determine whether p53 mutations were also present in MALT lymphoma, we evaluated specimens from eight patients (six gastric specimens, one parotid, and one from the small bowel) for p53 mutations using polymerase chain reaction and single strand conformational polymorphism analysis. Exon-4 through exon-8 were evaluated, because these are common sites of p53 mutation. In addition, tissues from 15 patients with MALT (including seven studied by single strand conformational polymorphism analysis) were examined for expression of p53 gene protein product by immunohistochemical techniques. All specimens were negative for p53 mutations, suggesting that mechanisms of lymphomagenesis are different for MALT than for splenic marginal zone lymphomas. Despite the absence of p53 point mutations, p53 gene product was localized in tissues from three of 15 patients with MALT. Staining was restricted to nuclei of neoplastic cells and was present in less than 10% of the cells. In summary, low-grade MALT lymphomas differ from marginal zone lymphomas in lacking p53 point mutations, although some patients express low levels of p53 gene product.
