DJ-1 Oncoprotein Profile in a Uveal Melanoma with Extraocular Extension: Immunohistochemical, Secretome Proteomics and Determination in Serum

Abstract

Purpose: : DJ-1 is an oncoprotein whose expression has been found in several types of human cancer. Our group has previously described its overexpression in uveal melanoma (UM) tumors and its presence in tumor secretomes and patients sera by proteomics approaches. The aim of this work was to investigate the expression of DJ-1 within the tumor mass and its presence at extracellular level in a case of UM with extraocular extension.

Methods: : A radical treatment (enucleation) was indicated in a 67 year-old Caucasian woman diagnosed with large choroidal melanoma with a large extraocular extension identified by ultrasonography in her left eye. A fragment of this tumor was processed by immunohistochemical techniques for DJ-1 protein staining. Other fragment was incubated in vitro for 24 hours in serum-free DMEM for tumor secretome collection. Additionally, a vitreous sample and serum from peripheral blood (taken before surgery) were also collected. A quantitative analysis of DJ-1 level in serum, vitreous and secretome samples was performed using a commercial ELISA analysis kit.

Results: : A strong immunohistochemical DJ-1 staining was detected in nucleus, cytoplasm and cell membrane on a high percentage of malignant cells with shape and tissue arrangement belonging to an epithelioid pattern. The DJ-1 analysis by ELISA showed high levels of this protein in the tumor secretome and patient serum compared to healthy population. Moreover, DJ-1 could also be detected in the vitreous sample.

Conclusions: : DJ-1 is ubiquity expressed by a high percentage of cells in UM. Moreover, these cells secrete this protein to culture media or sera. These results should be investigated in a large number of affected patients to evaluate this oncoprotein as a possible UM biomarker.

Keywords: melanoma • uvea • tumors