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Sarah E. Coupland, Helen Kalirai, Periklis Katopodis, Heinrich Heimann, Miltiadis Fiorentzis; Adipophilin expression in primary and metastatic uveal melanoma: a pilot study. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2500.
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© ARVO (1962-2015); The Authors (2016-present)
Adjustment of cancer cell metabolism to enable rapid cell growth and division is firmly established as one on the hallmarks of cancer. One of the changes associated with this metabolic phenotype is an over-activation of lipogenic pathways, characterized by high lipid droplet (LD) content in the cytoplasm of the cancer cells. The presence of large numbers of LDs has also been associated with chemoresistance. Adipophilin (ADP) is a protein that regulates the structure and formation of these LDs. Our observations of lipid droplets in UM cell lines led us to undertake this pilot study in which we evaluated the expression of ADP in uveal melanoma (UM).
Immunohistochemical analysis of ADP expression was performed in 34 consecutive enucleation specimens from 22 male and 12 female patients. These comprised 22 choroidal (64.7%) and 12 (35.3%) ciliochoroidal UM. The intensity of staining (IS) and the proportion of tumour cells stained (PS) for ADP were evaluated semiquantitatively on a scale 1-4. The total expression of ADP (tADP) was obtained by multiplying IS and PS scores together. Results were compared with clinical and histological parameters. In addition, 5 UM metastases to the liver were examined for ADP expression.
The median age of the primary UM patients at diagnosis was 72.5 years (range 44 - 90). The tumours had a mean largest basal diameter (LBD) of 12.04mm and a mean thickness of 7.7mm. Seventeen UM (50%) contained epithelioid cells, and 21 cases (61.7%) were classified as monosomy 3 by Multiplex Ligation Dependant Probe Amplification (MLPA).ADP was detected in all UM examined, although the proportion of UM cells containing ADP+ LD was variable across the tumour sections analysed. High ADP expression (tADP score >4) was documented in 17 specimens; however, this was not significantly correlated with any clinical, histological or genetic parameters. Notably, normal choroidal melanocytes in the enucleated eyes were ADP negative. Further, all examined hepatic UM metastases were ADP+, with most showing scores of >4 and with the surrounding liver parenchyma being ADP negative.
This is the first description of ADP protein expression in a small cohort of primary and metastatic UM. Understanding the biological significance of this trait of altered energy metabolism in UM may enable the development of therapies aimed at tumour cell metabolism.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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