scholarly journals HSP-27 protein expression in uveal melanoma: correlation with predicted survival

2010 ◽  
Vol 90 (6) ◽  
pp. 534-539 ◽  
Author(s):  
Fidan Jmor ◽  
Helen Kalirai ◽  
Azzam Taktak ◽  
Bertil Damato ◽  
Sarah E. Coupland
Keyword(s):  
Protein Expression ◽  
Uveal Melanoma ◽  
Hsp 27

scholarly journals Transcriptome Profiling Reveals New Insights into the Immune Microenvironment and Upregulation of Novel Biomarkers in Metastatic Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2832 ◽  
Author(s):  
Yamini Krishna ◽  
Amelia Acha-Sagredo ◽  
Dorota Sabat-Pośpiech ◽  
Natalie Kipling ◽  
Kim Clarke ◽  
...  
Keyword(s):  
Protein Expression ◽  
Uveal Melanoma ◽  
Transcriptome Profiling ◽  
Epithelioid Cell ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Galectin 3 ◽  
Novel Biomarkers ◽  
And Control ◽  
Infiltrating Lymphocytes

Metastatic uveal melanoma (mUM) to the liver is incurable. Transcriptome profiling of 40 formalin-fixed paraffin-embedded mUM liver resections and 6 control liver specimens was undertaken. mUMs were assessed for morphology, nuclear BAP1 (nBAP1) expression, and their tumour microenvironments (TME) using an “immunoscore” (absent/altered/high) for tumour-infiltrating lymphocytes (TILs) and macrophages (TAMs). Transcriptomes were compared between mUM and control liver; intersegmental and intratumoural analyses were also undertaken. Most mUM were epithelioid cell-type (75%), amelanotic (55%), and nBAP1-ve (70%). They had intermediate (68%) or absent (15%) immunoscores for TILs and intermediate (53%) or high (45%) immunoscores for TAMs. M2-TAMs were dominant in the mUM-TME, with upregulated expression of ANXA1, CD74, CXCR4, MIF, STAT3, PLA2G6, and TGFB1. Compared to control liver, mUM showed significant (p < 0.01) upregulation of 10 genes: DUSP4, PRAME, CD44, IRF4/MUM1, BCL2, CD146/MCAM/MUC18, IGF1R, PNMA1, MFGE8/lactadherin, and LGALS3/Galectin-3. Protein expression of DUSP4, CD44, IRF4, BCL-2, CD146, and IGF1R was validated in all mUMs, whereas protein expression of PRAME was validated in 10% cases; LGALS3 stained TAMs, and MFGEF8 highlighted bile ducts only. Intersegmental mUMs show differing transcriptomes, whereas those within a single mUM were similar. Our results show that M2-TAMs dominate mUM-TME with upregulation of genes contributing to immunosuppression. mUM significantly overexpress genes with targetable signalling pathways, and yet these may differ between intersegmental lesions.

scholarly journals Lack of BAP1 protein expression in uveal melanoma is associated with increased metastatic risk and has utility in routine prognostic testing

2014 ◽  
Vol 111 (7) ◽  
pp. 1373-1380 ◽  
Author(s):  
H Kalirai ◽  
A Dodson ◽  
S Faqir ◽  
B E Damato ◽  
S E Coupland
Keyword(s):  
Protein Expression ◽  
Uveal Melanoma ◽  
Metastatic Risk

JARID1B Protein Expression and Prognostic Implications in Uveal Melanoma

2012 ◽  
Vol 53 (8) ◽  
pp. 4442 ◽  
Author(s):  
Patrik Radberger ◽  
Agatha Radberger ◽  
Vladimir J. N. Bykov ◽  
Stefan Seregard ◽  
Mario A. Economou
Keyword(s):  
Protein Expression ◽  
Uveal Melanoma ◽  
Prognostic Implications

The prognostic value of cyclin D1, p53, and MDM2 protein expression in uveal melanoma

2000 ◽  
Vol 191 (2) ◽  
pp. 120-126 ◽  
Author(s):  
Sarah E. Coupland ◽  
Gerasimos Anastassiou ◽  
Andreas Stang ◽  
Harald Schilling ◽  
Ioannis Anagnostopoulos ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cyclin D1 ◽  
Uveal Melanoma ◽  
Prognostic Value ◽  
Mdm2 Protein

scholarly journals Inhibition of ATM Increases the Radiosensitivity of Uveal Melanoma Cells to Photons and Protons

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1388 ◽  
Author(s):  
Rumana N. Hussain ◽  
Sarah E. Coupland ◽  
Jakub Khzouz ◽  
Helen Kalirai ◽  
Jason L. Parsons
Keyword(s):  
Dna Repair ◽  
Protein Expression ◽  
Cell Lines ◽  
Uveal Melanoma ◽  
Primary Tumour ◽  
X Rays ◽  
Proton Beam Radiotherapy ◽  
Significant Difference ◽  
Atm Protein ◽  
Tissue Reactions

Treatment of uveal melanoma (UM) is generally successful, with local primary tumour control being at 90%–95%. Localized radiotherapy in the form of plaque brachytherapy or proton beam radiotherapy is the most common treatment modality in the UK. However, the basic mechanisms of radiation response, DNA repair and tissue reactions in UM have not been well documented previously. We have investigated the comparative radiosensitivity of four UM cell lines in response to exogenous radiation sources (both X-rays and protons), and correlated this with DNA repair protein expression and repair efficiency. We observed a broad range of radiosensitivity of different UM cell lines to X-rays and protons, with increased radioresistance correlating with elevated protein expression of ataxia telangiectasia mutated (ATM), a protein kinase involved in the signaling and repair of DNA double strand breaks. The use of an ATM inhibitor in UM cell lines enhanced radiosensitivity following both X-ray and proton irradiation, particularly in cells that contained high levels of ATM protein which are otherwise comparatively radioresistant. In proton-irradiated compared with non-irradiated primary enucleated UM patient samples, there was no significant difference in ATM protein expression. Our study therefore suggests that ATM is a potential target for increasing the radiosensitivity of more resistant UM subgroups.

Heat Shock Protein Expression in the Eye and in Uveal Melanoma

2003 ◽  
Vol 44 (7) ◽  
pp. 3059 ◽  
Author(s):  
Guy S. Missotten ◽  
Johanna G. Journe´e-de Korver ◽  
Didi de Wolff-Rouendaal ◽  
Jan E. Keunen ◽  
Reinier O. Schlingemann ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Protein Expression ◽  
Uveal Melanoma ◽  
Heat Shock Protein Expression

scholarly journals Patterns of BAP1 protein expression provide insights into prognostic significance and the biology of uveal melanoma

2017 ◽  
Vol 4 (1) ◽  
pp. 26-38 ◽  
Author(s):  
Neil Farquhar ◽  
Sophie Thornton ◽  
Sarah E Coupland ◽  
Judy M Coulson ◽  
Joseph J Sacco ◽  
...  
Keyword(s):  
Protein Expression ◽  
Uveal Melanoma ◽  
Prognostic Significance

scholarly journals Estimation of the timing of BAP1 mutation in uveal melanoma progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ogul E. Uner ◽  
Thonnie Rose O. See ◽  
Eszter Szalai ◽  
Hans E. Grossniklaus ◽  
Gustav Stålhammar
Keyword(s):  
Protein Expression ◽  
Tumor Cells ◽  
Uveal Melanoma ◽  
Primary Tumor ◽  
Tumor Initiation ◽  
Malignant Cells ◽  
Melanoma Progression ◽  
Uveal Melanomas

AbstractUveal melanoma is the most common primary intraocular malignancy. A vast majority of metastasizing tumors have mutations in the BAP1 gene. Here, we investigate the spatiotemporal timing of these mutations. The size of 177 uveal melanomas and 8.3 million individual tumor cells was measured. BAP1 sequencing results and BAP1 IHC were available and for 76 (43%) and 101 (57%) of these, respectively. Tumors with a BAP1 mutation had significantly larger volume (2109 vs. 1552 mm3, p = 0.025). Similarly, tumor cells with loss of BAP1 protein expression had significantly larger volume (2657 vs. 1593 μm3, p = 0.027). Using observations of the time elapsed between mitoses, the BAP1 mutation was calculated to occur when the primary tumor had a size of a few malignant cells to 6 mm3, 0.5 to 4.6 years after tumor initiation and at least 9 years before diagnosis. We conclude that BAP1 mutations occur early in the growth of uveal melanoma, well before the average tumor is diagnosed. Its timing coincides with the seeding of micrometastases.

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