Journal de pathologie clinique et expérimentale

Abstrait

Expression of Silent Information Regulator-1(Sirt1), CD163 and Tryptase; Implications for Immune Dys-regulation, Prognosis and Therapeutic Targeting in Classical Hodgkin Lymphoma

Harb OA, Mohamed MS, Ahmed RZ, Alattar AZ and Gertallah LM

Background: Many studies have assessed the relation between cHL histology and its clinical outcome but the results are still controversial. The most recent issue was the discovery of the methods of interaction between the elements of benign reactive inflammatory cells and their effect on cHL metabolism. Silent information regulator-1 (Sirt1) is a class III HDACs family member, it was expressed in T-cell lymphoma and was considered a recently discovered therapeutic target, we tried to detect that the significance of Sirt1 expression in malignant Reed-Sternberg cells and surrounding inflammatory infiltrate in cHL. Cluster of Differentiation 163 (CD163) is a scavenger receptor cystein-rich (SRCR) family member which identifies monocytes and macrophages, Tryptase is the secretory granules that were serine proteinase derived and it has been used as a mast cell activation marker. The tumor-infiltrating macrophages and mast cells have been found to have different roles in malignancies of many organs but their role in cHL prognosis had not been sufficiently clarified.

Aim of the work: To assess the influence of Sirt1 expression in the malignant cells and the surrounding tumor microenvironment CD163 positive macrophages and tryptase positive mast cells on the pathological parameters and clinical outcome in cHL patients.

Methods: We evaluated clinicopathological and prognostic significance of Sirt1, CD163 and tryptase expressions in sections from fifty paraffin blocks of cHL using immunehistochemistry.

Results: The expression of Sirt1 in cHL was associated with advanced stage of the disease, presence of B symptoms, splenic affection, (p<0.001), bone marrow infiltration (p=0.002) and the presence of bulky mediastinal lymph node (p=0.004). The expression of CD163 and tryptase in cHL was associated with advanced stage of the disease and the presence of bulky mediastinal lymph node (p<0.001). High Sirt1, tryptase and CD163 expression was associated with poor response to therapy, high incidence of relapse after successful therapy and poor three-year overall survival rate (p<0.001).

Conclusion: High levels of expression of Sirt1, CD163 and tryptase were found to be markers of poor prognosis in cHL.