Abstract
Purpose :
DJ-1 (PARK7) is an oncogene involved in the anti-apoptotic function and associated with Parkinson’s disease. Its over-expression has been observed in malignant tumors such as breast, lung, prostate, cervical, thyroid and pancreatic cancer and is correlated with tumor progression in lung cancer, esophageal and squamous cell carcinoma. On the other hand, SMAD7 is a protein-coding gene inhibitor of TGF-BETA and is associated with colorectal and breast cancer as well as skin melanoma. Its high expression has also been associated with high tumor thickness, higher mitotic rate, and presence of ulceration. The aim of this study is to evaluate the expression of PARK7 and SMAD7 expression in uveal melanoma (UM).
Methods :
Twenty-six formalin-fixed, paraffin-embedded UM were immunostained with monoclonal anti-PARK7 and monoclonal anti-SMAD7 antibodies using the Ventana Benchmark Automated Platform. Slides were then digitalized using the Zeiss AxioScan.Z1 scanner and their expression was evaluated by extension (EXT) and intensity. EXT was scored from 0-2, where 0 corresponded to no staining, 1 for focal and 2 for diffuse. Moreover, intensity was graded as 0, 1, or 2, corresponding to no staining, weak, or strong respectively. Biostatistics was performed using the Pearson chi-square test with Statistica 8.0 SPSS22 software.
Results :
All the 26 samples were positive for PARK7. Grade 1 intensity was found in 6 (23.0%) samples and grade 2 in 20 (77.0%). On the other hand, grade 1 EXT was found in 2 cases (7.0%) and grade 2 in 24 (93.0%). Regarding SMAD7, all 26 specimens were positive. Grade 1 and 2 intensity was equally distributed in all samples (13 each, 50%). Grade 1 EXT was found in 9 cases (34.61%) and grade 2 in 17 (65.38%).
Conclusions :
PARK7 and SMAD7 were expressed in all uveal melanoma eyes. The vast majority of PARK7 cases revealed a strong and diffuse expression, while SMAD7 cases were strong and diffuse in half of the cases. This result indicates that both PARK7 and SMAD7 are candidates to be potential therapeutic targets in uveal melanoma. Correlation with histopathological prognostic factors is underway to further clarify the significance of these findings in uveal melanoma.
This is a 2020 ARVO Annual Meeting abstract.