Abstract
Purpose: :
Uveal Melanoma (UM) is the most common primary intraocular malignant tumor in adults. Preferentially expressed antigen of melanoma (PRAME) is a protein expressed in a wide variety of tumors, such as melanomas, non-small cell lung carcinomas, sarcomas, head and neck tumors and renal carcinomas, as well as in normal testis. Its overexpression has been linked to a repression of the Retinoic Acid Receptor signaling in cancers. This in turn presents the tumor with an advantage for growth and survival. However, PRAME is also recognized by cytolytic T-cells. Therefore, PRAME could be a potential target for immunotherapy. The aim of this experiment is to study the expression of PRAME in UM and verify its correlation with the prognostic factors.
Methods: :
Seventeen cases of paraffin-embedded human UM tissues were immunostained with a rabbit polyclonal antibody to PRAME. This was done using the Ventana BenchMark fully automated machine. Clinical pathological data was obtained based on age, location of tumor, size of tumor, cell type, metastasis and follow up. The staining results were graded based on the sum of the percentage and intensity of staining. Samples were then classified into two groups (Low and high expression). A survival analysis for these cases was also performed using the Kaplan-Meier test.
Results: :
Seventy-six percent (13 of 17) of the human UM samples stained positive for PRAME. This high positive staining indicates a strong presence of PRAME in these tissues. There was no correlation between the staining results and prognostics factors.
Conclusions: :
PRAME is expressed in the majority of UM cases. To the best of our knowledge this is the first study examining the presence of PRAME in UM. In cutaneous melanoma, PRAME knockdown restored retinoic acid signalling and inhibited growth in a xenograft model. Further experimentation with larger samples and metastatic tissue is warranted to confirm its relevance for UM patients.
Keywords: tumors • immunohistochemistry • melanoma