PRAME expression in Hodgkin's lymphoma and its clinical significance

Introduction and Aim: It is necessary to define new targets in order to develop new treatment strategies in cases with chemo-resistant Hodgkin Lymphoma. PRAME (Preferentially expressed antigen of melanoma) has become a promising candidate for tumour immunotherapy since it was detected that it is recognized by the autologous cytotoxic T lymphocytes. PRAME is not expressed or mildly expressed in normal tissues except for the testicle, ovary, endometrium and adrenals while it is expressed in high levels in many solid tumours and hematologic malignancies. There is little information on the PRAME expression in Hodgkin Lymphoma. The purpose of this study was to examine PRAME expression in Hodgkin Lymphoma, to understand its relation with the known prognostic factors, and to detect the usability of PRAME as target molecule for immunotherapy in Hodgkin Lymphoma. In addition, the aim was to compare the Real-Time Polymerase Chain Reaction and Immunohistochemistry methods by using those two methods.Materials and methods: The study covered 110 patients who were diagnosed with Hodgkin Lymphoma and whose samples and clinical follow-ups could be accessed. Demographic, clinic, laboratory and prognostic values of the patients were recorded retrospectively. Out of 110 cases, biopsy samples could be accessed for a total of 82 patients. PRAME was studied in the tissue samples of those patients through Immunohistochemistry and Real-Time Polymerase Chain Reaction methods. Data was tested by using appropriate statistical methods.Results: PRAME was detected in 15 (18.3%) patients with Immunohistochemistry and in 8 (9.8%) patients with Real-Time Polymerase Chain Reaction. International Prognostic Score was 4 and above in the cases that were detected with PRAME expression, and this figure was found to be significantly significant in PRAME positive cases (p: 0.039). Disease-Free Survival and Overall Survival was analysed for the 82 patients for whom PRAME was studied. Overall Survival was found to be shorter in cases with PRAME positive as compared with PRAME negative with Real-Time Polymerase Chain Reaction, (p:0.0005). Similarly Disease-Free Survival and Overall Survival were found to be shorter in PRAME positive cases by using Immunohistochemistry but this did not reach a statistical significance. Disease-Free Survival was shorter depending on being over the age of 45, in the advanced phase of disease, in the high-risk group, having high International Prognostic Score and relapsing before 12 months. When the independent factors affecting Overall Survival and Disease-Free Survival were considered, it was seen that only advanced age and high-risk group were the independent factors affecting survival. Although being PRAME positive increases the mortality risk (or: 3.56) this was not found statistically significant.Conclusion: It was found that Real-Time Polymerase Chain Reaction was found to be more sensitive method in detecting PRAME expression. Immunohistochemistry is also a useful method for PRAME analysis. Particularly showing the PRAME expression in Histiocytes and Reed Stenberg cells can be a guide for future studies. These results indicate that PRAME expression can be an adverse prognostic parameters in Hodgkin Lymphoma.