Proteomics of Uveal Melanoma: A Minireview

Uveal melanoma, which is the most common primary intraocular malignancy in adults, arises from melanocytes within the iris, ciliary body and choroid. The diagnosis is based principally on clinical examination of the tumor with biomicroscopy and indirect ophthalmoscopy and confirmed by diagnostic techniques such as ultrasonography, fundus fluorescein angiography and optical coherence tomography. The clinical diagnosis of posterior uveal melanomas can be made when the classical appearance of a pigmented dome-shaped mass is detected on dilated fundus exam. Uveal melanomas classically show low to medium reflectivity on A-scan ultrasonography and on B-scan ultrasonography the tumor appears as a hyperechoic, acoustically hollow intraocular mass. Management of a suspicious pigmented lesion is determined by its risk factors of transforming into a choroidal melanoma, such as documentation of growth, thickness greater than 2 mm, presence of subretinal fluid, symptoms and orange pigment, margin within 3 mm of the optic disc, and absence of halo and drusen. Advances in the diagnosis and local and systemic treatment of uveal melanoma have caused a shift from enucleation to eye-conserving treatment modalities including transpupillary thermotherapy and radiotherapy over the past few decades. Prognosis can be most accurately predicted by genetic profiling of fine needle aspiration biopsy of the tumor before the treatment, and high-risk patients can now be identified for clinical trials that may lead to target-based therapies for metastatic disease and adjuvant therapy which aims to prevent metastatic disease.

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“…Elevated expression of S100, MCAM, NKI-C3, E-cadherin, c-Met and MIA has been demonstrated in the tissue of metastatic melanomas. 175 …”

Section: Introductionmentioning

confidence: 99%

Uveal Melanoma; Current Trends in The Diagnosis and Management

Tarlan

Kıratlı

2016

tjo

104

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“… 1 UM is the most common intraocular tumor and its prognosis depends on the size of the primary tumor, the time of diagnosis, and the presence of metastases. 2 A number of clinical and histological risk factors have been defined over the last three decades, among others – clinicopathological factors like location, extraocular growth, involvement of the CB, and the epitheloid cell type of the tumor. 3 Larger tumors are associated with a mortality rate of ~50% shortly after the diagnosis, while patients with medium-sized tumors show 50% survival rate over 15 years measured from primary tumor treatment.…”

Section: Introductionmentioning

confidence: 99%

“… 3 Larger tumors are associated with a mortality rate of ~50% shortly after the diagnosis, while patients with medium-sized tumors show 50% survival rate over 15 years measured from primary tumor treatment. 2 Nearly 50% of patients suffering from UM develop metastatic disease, that usually involves the liver and is almost inevitably fatal. 4 When metastases develop, the median survival of the patients is only 5–7 months.…”

Section: Introductionmentioning

confidence: 99%

Characterization of luteinizing hormone-releasing hormone receptor type I (LH-RH-I) as a potential molecular target in OCM-1 and OCM-3 human uveal melanoma cell lines

Sipos¹,

Dobos²,

Rózsa³

et al. 2018

OTT

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IntroductionUveal melanoma (UM) is the most common primary intraocular malignancy with very poor prognosis. Conventional chemotherapy only rarely prolongs the survival, therefore patients require novel treatment modalities. The discovery of specific receptors for hypothalamic hormones on cancer cells has led to the development of radiolabeled and cytotoxic hormone analogs.Materials and methodsIn the present study, our aim was to investigate the expression of mRNA for receptors of luteinizing hormone-releasing hormone type I (LH-RH-I) and LH-RH ligand in OCM-1 and OCM-3 human uveal melanoma cell lines. The presence and binding characteristics of LH-RH-I receptor protein was further studied by Western blot, immunocytochemistry and ligand competition assay. The expression of mRNA and protein for LH-RH-I receptors has been also studied using tumor samples originating from nude mice xenografted with OCM-1 or OCM-3 cells.ResultsThe mRNA for LH-RH-I receptor has been detected in OCM-1 and OCM-3 cell lines and was found markedly higher in OCM-3 cells. The mRNA for LH-RH-I receptors was also observed in both UM xenograft models in vivo with higher levels in OCM-3. The presence of LH-RH-I receptor protein was found in both cell lines in vitro by immunocytochemistry and Western blot, and also in tumor tissue samples grown in nude mice by Western blot. Both human uveal melanoma models investigated showed specific high affinity receptors for LH-RH-I using ligand competition assay. The mRNA for LH-RH ligand has also been detected in OCM-1 and OCM-3 cell lines and cancer tissues.ConclusionThe demonstration of the expression of LH-RH-I receptors in OCM-1 and OCM-3 human UM cell lines suggests that they could serve as potential molecular target for therapy. Our findings support the development of new therapeutic approaches based on cytotoxic LH-RH analogs or modern powerful antagonistic analogs of LH-RH targeting LH-RH-I receptors in UM.

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“…Monosomy 3 strongly predicts metastatic risk and other chromosomal abnormalities, also correlated with metastatic diseases (3,4). Approximately half of the patients develop metastases, most frequently in the liver (5,6). Monosomy 3 correlates with epitheloid histology, ciliary body involvement and poor outcome (6).…”

Section: Introductionmentioning

confidence: 99%

“…Approximately half of the patients develop metastases, most frequently in the liver (5,6). Monosomy 3 correlates with epitheloid histology, ciliary body involvement and poor outcome (6). Lack of chromosome 3 has been demonstrated in 5–10% of all the patients, and the remaining copy is duplicated (7).…”

Section: Introductionmentioning

confidence: 99%

Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma

et al. 2017

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Uveal melanoma (UM) is the most common primary intraocular malignancy with a very poor prognosis. The most frequent chromosome aberration in UM is the monosomy of chromosome 3. Previously, we demonstrated that ~50% of UMs express type-I receptor for luteinizing hormone-releasing hormone (LH-RH-R). The gene encoding LH-RH-R is located in chromosome 4 (location: 4q21.2); however, the occurrence of numerical aberrations of chromosome 4 have never been studied in UM. In the present study, we investigated the abnormalities of chromosome 3 and 4, and the possible correlation between them, as well as with LH-RH-R expression. Forty-six specimens of UM were obtained after enucleation. Numerical aberrations of chromosome 3 and 4 were studied by fluorescence in situ hybridization (FISH). Chromosome 4 was detected in normal biparental disomy only in 14 (30%) samples; however, 32 cases (70%) showed more than 2 signals/nucleus. Monosomy of chromosome 3 could be found in 16 (35%) samples. In 6 specimens (13%), more than 2 copies of chromosome 3 were found, while normal biparental disomy was detected in 24 (52%) samples. Statistical analysis indicated a statistically significant (p<0.05) correlation between the copy number of chromosome 3 and 4. Moreover, moderate difference was revealed in the survival rate of the UM patients with various pathological profiles. No correlation was found between chromosome aberrations and LH-RH-R expression. Our results clearly demonstrate abnormalities in chromosome 3 and 4 and the incidence of the monosomy of chromosome 3 in human UM. In summary, our results provide new incite concerning the genetic background of this tumor. Our findings could contribute to a more precise determination of the prognosis of human UM and to the development of new therapeutic approaches to this malignancy.

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Proteomics of Uveal Melanoma: A Minireview

Cited by 12 publications

References 52 publications

Uveal Melanoma; Current Trends in The Diagnosis and Management

Uveal Melanoma; Current Trends in The Diagnosis and Management

Characterization of luteinizing hormone-releasing hormone receptor type I (LH-RH-I) as a potential molecular target in OCM-1 and OCM-3 human uveal melanoma cell lines

Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma

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