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Uveal metastasis

Lei Sun, Peng Sun, Qi-Ying Zhou, Xiangchun Gao, Qing Han
Increasing evidences have demonstrated that long noncoding RNAs (LncRNAs) play a significant role in the development of tumor. However, the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in uveal melanoma remains unknown. In this study, we demonstrated that the expression of MALAT1 was upregulated in the uveal melanoma tissues compared to normal tissues. Among them, MALAT1 was upregulated in 72% (18/25) uveal melanoma tissues compared to their paired normal tissues. Knockdown of MALAT1 suppressed uveal melanoma cell proliferation, colony information, invasion and migration...
2016: American Journal of Translational Research
Frédéric Mouriaux, Karine Zaniolo, Marjorie-Allison Bergeron, Cindy Weidmann, Arnaud De La Fouchardière, Frédéric Fournier, Arnaud Droit, Mohib W Morcos, Solange Landreville, Sylvain L Guérin
Purpose: Development of liver metastasis remains the most common cause of mortality in uveal melanoma (UM). A few cell lines cultured from primary UM tumors have been used widely to investigate the pathobiology of UM. However, the translation of basic knowledge to the clinic for the treatment of the metastatic disease has remained incremental at best. In this study, we examined whether the properties of UM cell lines at various passages were similar to their corresponding primary tumors...
October 1, 2016: Investigative Ophthalmology & Visual Science
Hildur Helgadottir, Veronica Höiom
Uveal melanoma (UM) is the most common malignant eye tumor in adults affecting ~7,000 individuals per year worldwide. UM is a rare subtype of melanoma with distinct clinical and molecular features as compared to other melanoma subtypes. UMs lack the most typical cutaneous melanoma-associated mutations (BRAF, NRAS, and NF1) and are instead characterized by a different set of genes with oncogenic or loss-of-function mutations. By next-generation sequencing efforts on UM tumors, several driver genes have been detected...
2016: Application of Clinical Genetics
P Justusová, M Štubňa, M Veselovský, B Lipková
INTRODUCTION: Uveal melanoma is the most common primary intraocular tumour in adults in Caucasians and in 75% is arising from choroid. It threatens not only the patients loss of vision and eye, but also 50% of patients after 5-year interval after therapy die due to distant metastases. The treatment of small and medium-sized melanoma are methods preserving eye globe. Almost half of the total number of patients is still unavoidable enucleation. Considerably rarer is indicated exenteration of an orbit...
2016: Ceská a Slovenská Oftalmologie
Tara A McCannel, Mitchell Kamrava, Jeffrey Demanes, James Lamb, John D Bartlett, Robert Almanzor, Melissa Chun, Colin A McCannel
PURPOSE: To review outcomes in mostly large uveal melanoma treated with a 23-mm-diameter iodine-125 plaque, the largest size available at our center, and the influence of vitrectomy and silicone oil 1000 centistokes for radiation attenuation. METHODS: A one-to-one matched case-control comparison was performed. Case patients were treated with a 23-mm-diameter iodine-125 plaque and vitrectomy with silicone oil 1000-cSt placement. Control cases, treated with 23-mm plaque alone, were matched to cases with respect to tumor size and distance from tumor apex to optic nerve and fovea...
September 16, 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
Pablo Zoroquiain, Erin Mayo-Goldberg, Sarah Alghamdi, Sulaiman Alhumaid, Eduardo Perlmann, Paulo Barros, Nancy Mayo, Miguel N Burnier
The cutoff presented in the current classification of canine melanocytic lesions by Wilcock and Pfeiffer is based on the clinical outcome rather than morphological concepts. Classification of tumors based on morphology or molecular signatures is the key to identifying new therapies or prognostic factors. Therefore, the aim of this study was to analyze morphological findings in canine melanocytic lesions based on classic malignant morphologic principles of neoplasia and to compare these features with human uveal melanoma (HUM) samples...
August 26, 2016: Melanoma Research
Powrnima Joshi, Mitra Kooshki, Wayne Aldrich, Daniel Varghai, Maciej Zborowski, Arun D Singh, Pierre L Triozzi
Natural killer (NK) cells are implicated in the control of metastasis in uveal melanoma, a process that has been ascribed to its cancer stem cell subpopulation. NK cell activation is regulated by specific microRNA (miR). The NK cell sensitivity and regulatory miR production of uveal melanoma cancer stem cells was examined. Cancer stem cells enriched from aggressively metastatic MUM2B uveal melanoma cells by selecting CD271(+) cells or propagating as non-adherent spheres in stem-cell supportive were more resistant to NK cell cytolysis than cancer stem cells enriched from less aggressively metastatic OCM1 uveal melanoma cells...
August 26, 2016: Clinical & Experimental Metastasis
Ahmed Zewar, Ibrahim Nawaiseh, Imad Jaradat, Jakub Khzouz, Khaleel Alrawashdeh, Ghadeer Abdeen, Mustafa Mehyar, Samer Khurma, Yacoub A Yousef
OBJECTIVE: The aim of this study was evaluate the features and outcome of management of uveal melanoma in King Hussein Cancer Center as an example of a referral tertiary cancer center in the Middle East. MATERIAL AND METHOD: This was aetrospective, observational case series of 46 eyes of 46 patients with uveal melanoma. Data collection required access to medical records, radiology and pathology reports, and laboratory results. The main outcome measures included age at diagnosis, tumor location and dimensions, TNM stage, treatment modality, visual outcome, metastasis, and mortality...
2016: Türk Patoloji Dergisi
Rosario Caltabiano, Lidia Puzzo, Valeria Barresi, Antonio Ieni, Carla Loreto, Giuseppe Musumeci, Paola Castrogiovanni, Marco Ragusa, Pietro Foti, Andrea Russo, Antonio Longo, Michele Reibaldi
Uveal melanoma is the most frequent primary intraocular neoplasm in adults. Although malignant melanoma may be located at any point in the uveal tract, the choroid and ciliary body are more frequent locations than the iris. In the present study, we examined ADAM10 expression levels in primary uveal melanoma both with and without metastasis, and we evaluated their association with other high risk characteristics for metastasis in order to assess if ADAM10 can be used to predict metastasis. This study included a total of 52 patients, 23 men and 29 women, with uveal melanoma...
August 9, 2016: Pathology, Research and Practice
Adriana Amaro, Federica Parodi, Konrad Diedrich, Giovanna Angelini, Cornelia Götz, Silvia Viaggi, Irena Maric, Domenico Coviello, Maria Pia Pistillo, Anna Morabito, Mario Mandalà, Paola Ghiorzo, Paola Visconti, Marina Gualco, Luca Anselmi, Roberto Puzone, Francesco Lanza, Carlo Mosci, Federica Raggi, Maria Carla Bosco, Luigi Varesio, Michael Zeschnigk, Laura Spano, Paola Queirolo, Ulrich Pfeffer
Importance: Chromosome 6p amplification is associated with more benign behavior for uveal melanomas (UMs) with an otherwise high risk of metastasis conferred by chromosome 3 monosomy. Chromosome 6p contains several members of the B7 family of immune regulator genes, including butyrophilin-like 2 (BTNL2; OMIM, 606000), which is associated with prostate cancer risk and autoimmune diseases. Objective: To investigate the expression and variant allele frequencies of BTNL2, a candidate gene for chromosome 6 amplification, in patients with UM...
October 1, 2016: JAMA Ophthalmology
Daniela Süsskind, José Hurst, Jens Martin Rohrbach, Sven Schnichels
BACKGROUND: To establish a mouse model with the aim of studying the tumour biology and metastasis formation of uveal melanoma. METHODS: Two human primary uveal melanoma cell lines (UMT2 and UMT42) were injected into the choroid of BALB/c nude mouse eyes. Intraocular tumour growth and metastasis formation in the liver and lungs were assessed after 13 to 22 weeks. Formalin-fixed, paraffin-embedded material was processed via haematoxylin and eosin staining for histological examination and periodic acid Schiff staining to search for extravascular matrix patterns...
August 9, 2016: Clinical & Experimental Ophthalmology
Matthew G Field, Michael A Durante, Christina L Decatur, Bercin Tarlan, Kristen M Oelschlager, John F Stone, Jeffim Kuznetsov, Anne M Bowcock, Stefan Kurtenbach, J William Harbour
BACKGROUND: We previously identified PRAME as a biomarker for metastatic risk in Class 1 uveal melanomas. In this study, we sought to define a threshold value for positive PRAME expression (PRAME+) in a large dataset, identify factors associated with PRAME expression, evaluate the prognostic value of PRAME in Class 2 uveal melanomas, and determine whether PRAME expression is associated with aberrant hypomethylation of the PRAME promoter. RESULTS: Among 678 samples analyzed by qPCR, 498 (73...
July 30, 2016: Oncotarget
Hans E Grossniklaus, Qing Zhang, Shuo You, Conni McCarthy, Steffen Heegaard, Sarah E Coupland
We examined liver specimens from 15 patients with uveal melanoma (UM) who had succumbed to their disseminated disease. We found two distinct growth patterns of UM metastasis: infiltrative (n=12) and nodular (n=3). In the infiltrative pattern, individual UM cells with a CD133+ cancer stem cell-like phenotype were present and formed aggregates of Stage I<50μm diameter micrometastases in the sinusoidal spaces. These micrometastases appeared to expand, destroy adjacent hepatocytes and form Stage II 51-500μm diameter and then Stage III >500μm diameter metastases, which were encapsulated by collagenized fibrous septae...
July 29, 2016: Human Pathology
Pierre L Triozzi, Susan Achberger, Wayne Aldrich, John W Crabb, Yogen Saunthararajah, Arun D Singh
BACKGROUND: Epigenetic events mediated by methylation and histone modifications have been associated with the development of metastasis in patients with uveal melanoma. The role of epigenetic events mediated by microRNA (miR) is less clear. Tumor and plasma miR expression was examined in patients with primary uveal melanoma with tumor monosomy-3, a predictor of metastasis. RESULTS: miR profiling of tumors by microarray found six miRs over-expressed and 19 under-expressed in 33 tumors with monosomy-3 compared to 22 without...
2016: Clinical Epigenetics
Kristen Meldi Plasseraud, Robert W Cook, Tony Tsai, Yevgeniy Shildkrot, Brooke Middlebrook, Derek Maetzold, Jeff Wilkinson, John Stone, Clare Johnson, Kristen Oelschlager, Thomas M Aaberg
Uveal melanoma management is challenging due to its metastatic propensity. DecisionDx-UM is a prospectively validated molecular test that interrogates primary tumor biology to provide objective information about metastatic potential that can be used in determining appropriate patient care. To evaluate the continued clinical validity and utility of DecisionDx-UM, beginning March 2010, 70 patients were enrolled in a prospective, multicenter, IRB-approved study to document patient management differences and clinical outcomes associated with low-risk Class 1 and high-risk Class 2 results indicated by DecisionDx-UM testing...
2016: Journal of Oncology
Aysegül Tura, Hartmut Merz, Mihaela Reinsberg, Matthias Lüke, Martine J Jager, Salvatore Grisanti, Julia Lüke
Monosomy-3 in primary uveal melanoma (UM) is associated with a high risk of metastasis and mortality. Although circulating melanoma cells (CMC) can be found in most UM patients, only approximately 50% of the patients develop metastases. We utilized a novel immuno-FISH assay to detect chromosome-3 in intact CMC isolated by dual immunomagnetic enrichment. Circulating melanoma cells were detected in 91% of the patients (n = 44) with primary non-metastatic UM, of which 58% were positive for monosomy-3. The monosomy-3 status of CMC corresponded to the monosomy-3 status of the primary tumor in 10 of the 11 patients where this could be tested...
September 2016: Pigment Cell & Melanoma Research
Yesim Erim, Jennifer Scheel, Anja Breidenstein, Claudia Hd Metz, Dietmar Lohmann, Hans-Christoph Friederich, Sefik Tagay
BACKGROUND: Uveal melanoma patients with a poor prognosis can be detected through genetic analysis of the tumor, which has a very high sensitivity. A large number of patients with uveal melanoma decide to receive information about their individual risk and therefore routine prognostic genetic testing is being carried out on a growing number of patients. It is obvious that a positive prediction for recidivism in the future will emotionally burden the respective patients, but research on the psychosocial impact of this innovative method is lacking...
2016: BMC Cancer
Esmeralda Delgado, João X Silva, Hugo Pissarra, Maria C Peleteiro, Richard R Dubielzig
This manuscript describes a previously unreported clinical case of canine uveal melanoma in a miniature Schnauzer dog with an unusual location of metastasis (prostate) and delayed occurrence (3 years after primary tumor diagnosis and enucleation). Immunohistochemical labeling of both tumors with Melan A, Ki-67, and c-kit added some valuable information.
July 2016: Clinical Case Reports
Marta M Stei, Karin U Loeffler, Frank G Holz, Martina C Herwig
Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocular injection of cutaneous melanoma cells may suit best for investigating immunologic/tumor biology aspects...
2016: BioMed Research International
Tero T Kivelä, Sophie Piperno-Neumann, Laurence Desjardins, Alexander Schmittel, Nikolaos Bechrakis, Edoardo Midena, Serge Leyvraz, Leonidas Zografos, Jean-Daniel Grange, Guillaume Ract-Madoux, Ernest Marshall, Bertil Damato, Sebastian Eskelin
PURPOSE: To validate a staging system for metastatic uveal melanoma that will facilitate planning, reporting, and interpreting the results of clinical trials. DESIGN: Reliability and validity study. METHODS: The performance index, the largest diameter of the largest metastasis and alkaline phosphatase level at the time of diagnosis of metastases, and overall survival of 249 patients from 7 ocular oncology centers who died of dissemination were analyzed...
August 2016: American Journal of Ophthalmology
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