Molecular pathology of uveal melanoma.

Like other cancers, uveal melanomas (UM) are characterised by an uncontrolled, clonal, cellular proliferation, occurring as a result of numerous genetic, and epigenetic aberrations. Signalling pathways known to be disrupted in UM include: (1) the retinoblastoma pathway, probably as a result of cyclin D1 overexpression; p53 signalling, possibly as a consequence of MDM2 overexpression; and the P13K/AKT and mitogen-activated protein kinase/extracellular signal-related kinase pathway pathways that are disturbed as a result of PTEN and GNAQ/11 mutations, respectively. Characteristic chromosomal abnormalities are common and include 6p gain, associated with a good prognosis, as well as 1p loss, 3 loss, and 8q gain, which correlate with high mortality.

Molecular pathology of lymphoma.

Ocular lymphomas can be divided into intraocular lymphomas and ocular adnexal lymphomas. The vitreoretinal lymphoma-usually a diffuse large B-cell lymphoma (DLBCL) of high-grade malignancy-is the most common lymphoid malignancy arising in the eye, while the extranodal marginal zone B-cell lymphoma (EMZL), an indolent often recurrent tumour, occurs most frequently in the ocular adnexal tissue. The two lymphoma subtypes differ significantly in their clinical presentation, subsequent course and outcome as well as in their underlying morphological, immunophenotypical and genetic features.

MRI in the detection of hepatic metastases from high-risk uveal melanoma: a prospective study in 188 patients.

Background/aims: To evaluate MRI in the detection of asymptomatic hepatic metastases from uveal melanoma.

Methods: A single-arm prospective cohort study.

Participants: We enrolled 188 patients whose predicted 5-year mortality from uveal melanoma exceeded 50%.

Proteomic analyses of the vitreous humour.

The human vitreous humour (VH) is a transparent, highly hydrated gel, which occupies the posterior segment of the eye between the lens and the retina. Physiological and pathological conditions of the retina are reflected in the protein composition of the VH, which can be sampled as part of routine surgical procedures. Historically, many studies have investigated levels of individual proteins in VH from healthy and diseased eyes.

Recovery of function following regeneration of the damaged retina in the adult newt, Notophthalmus viridescens.

The red-spotted newt, Notophthalmus viridescens, is one of few adult vertebrate organisms that has retained the remarkable ability to regenerate a complete retina following injury or removal. The aim of this study was to develop a non-invasive method to monitor recovery of components within the retinal circuitry, in vivo, following surgical removal (retinectomy) of the adult newt retina. A novel and reproducible protocol was established for full-field electroretinography in the intact newt retina.

IL-10 -1082 SNP and IL-10 in primary CNS and vitreoretinal lymphomas.

Objectives: Most primary central nervous system lymphomas (PCNSLs) and primary vitreoretinal lymphomas (PVRLs) are B-cell lymphomas that produce high levels of interleukin (IL)-10, which is linked to rapid disease progression. The IL-10 (-1082) G → A polymorphism (IL-10 SNP) is associated with improved survival in certain non-CNS lymphoma patients. PDCD4 is a tumor suppressor gene and upstream regulator of IL-10.

Epithelial tumours of the lacrimal gland: a clinical, histopathological, surgical and oncological survey.

Epithelial tumours of the lacrimal gland represent a large spectrum of lesions with similarities in clinical signs and symptoms but with different biological behaviour and prognosis. They are rare, but with aggressive malignant potential. Tumours of the lacrimal gland may present with swelling of the lacrimal gland, displacement of the eyeball, reduced eye motility and diplopia.

Ocular melanoma.

Ocular melanomas comprise uveal and conjunctival sub-types, which are very different from each other. A large majority of uveal melanomas involve the choroid, with less than 10% being confined to the ciliary body and iris. They tend to metastasize haematogenously, almost always involving the liver.

Discrepancy between fluorescence in situ hybridization and multiplex ligation-dependent probe amplification in orbital recurrence of uveal melanoma 26 years after enucleation.

Cytogenetic analysis has transformed the management of uveal melanoma in recent years and allows categorization of such tumors into low-grade tumors with a favorable prognosis and high-grade tumors that metastasize with a fatal outcome. The authors report the case of a 73-year-old man who presented with recurrent melanoma in his left socket, 26 years after enucleation for uveal melanoma. Chromosomal analysis by multiplex ligation-dependent probe amplification revealed partial loss of chromosome 3 and gains in chromosomes 6 and 8, which were missed with fluorescence in situ hybridization.

Comparison of formalin-fixed and snap-frozen samples analyzed by multiplex ligation-dependent probe amplification for prognostic testing in uveal melanoma.

Purpose: Survival of patients with uveal melanoma (UM) correlates strongly with chromosomal abnormalities, such as monosomy 3 and polysomy 8q. Studies have shown multiplex ligation-dependent probe amplification (MLPA) to detect reliably chromosomal aberrations in UM using frozen samples. To date, the concordance between MLPA data generated from frozen and fixed samples has not been investigated.

Cancer of the orbit and adnexa.

The diagnosis and treatment of orbital and periorbital malignancies are challenging. These tumors can result in blindness, death, and significant cosmetic deformities. Herein, we present the most common ocular malignancies and a systematic approach to diagnosis.

Differences in uveal melanomas between men and women from the British Isles.

Purpose: The purpose of this study is to compare uveal melanomas (UMs) in men and women.

Methods: The Liverpool Ocular Oncology Centre (LOOC) database was reviewed. Patients treated for UM at the LOOC between 1993 and 2010 were selected.

Primary vitreoretinal lymphoma: a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium.

Primary vitreoretinal lymphoma (PVRL), also known as primary intraocular lymphoma, is a rare malignancy typically classified as a diffuse large B-cell lymphoma and most frequently develops in elderly populations. PVRL commonly masquerades as posterior uveitis and has a unique tropism for the retina and central nervous system (CNS). Over 15% of primary CNS lymphoma patients develop intraocular lymphoma, usually occurring in the retina and/or vitreous.

Analysis of intraocular biopsies.

In this chapter, the importance of intraocular biopsies in the diagnosis/exclusion of ocular malignancies and prognostication is outlined. Despite improvements in ancillary studies in ophthalmology, intraocular biopsies are increasingly being performed in many ocular oncology centres. Experience is required in taking these biopsies, in their transport to the pathology laboratory, in their triaging and processing, and in their interpretation.

Clinical and pathologic characteristics of biopsy-proven iris melanoma: a multicenter international study.

Objective: To collaborate with multiple centers to identify representative epidemiological, clinical, and pathologic characteristics of melanoma of the iris. This international, multicenter, Internet-assisted study in ophthalmic oncology demonstrates the collaboration among eye cancer specialists to stage and describe the clinical and pathologic characteristics of biopsy-proven melanoma of the iris.

Methods: A computer program was created to allow for Internet-assisted multicenter, privacy-protected, online data entry.

Uveal melanoma cell lines contain stem-like cells that self-renew, produce differentiated progeny, and survive chemotherapy.

Purpose: Uveal melanoma (UM) cells in high-metastatic risk tumors have an undifferentiated molecular signature indicative of a more primitive cellular phenotype. Given mounting evidence for the existence of cancer stem cells (CSC), the authors investigated whether UM cell lines retain a population of self-renewing tumorigenic cells.

Methods: Single-cell cloning and spheroid culture studies were used to study the presence of a CSC-like population in two cell lines derived from the primary tumor (Mel270) and metastatic liver lesion (Omm2.

GDF-15: a novel serum marker for metastases in uveal melanoma patients.

Background: About 50% of patients with uveal melanoma (UM) develop metastases during the course of their disease. We analyzed serum levels of Growth Differentiation Factor-15 (GDF-15), with the aim of identifying patients with early metastases.

Methods: GDF-15 concentration was measured using an enzyme-linked immunosorbent assay (ELISA) in serum samples from 188 UM patients (170 patients without metastases; 18 patients with clinically detectable metastases) and 18 healthy control individuals.

Status of RASSF1A in uveal melanocytes and melanoma cells.

RASSF1A gene, found at the 3p21.3 locus, is a tumor suppressor gene frequently hypermethylated in human cancers. In this study, we report that compared with melanocytes in normal choroid, RASSF1A is downregulated in uveal melanoma samples and in uveal melanoma cell lines.

Combined p53 and MDM2 biomarker analysis shows a unique pattern of expression associated with poor prognosis in patients with renal cell carcinoma undergoing radical nephrectomy.

Objective: To resolve much debated issues surrounding p53 function, expression and mutation in renal cell carcinoma (RCC), we performed the first study to simultaneously determine p53/MDM2 expression, TP53 mutational status (in p53-positive patients) and outcome in RCC.

Patients And Methods: In total, 90 specimens obtained from patients with RCC, who were treated by radical nephrectomy, were analyzed by immunohistochemistry for p53 and MDM2 on a tissue microarray, and p53 was functionally and genetically analyzed in p53 positive samples. Outcome analysis was by the Kaplan-Meier method and univariate analysis was used to identify variables for subsequent multivariate analysis of correlations between clinical parameters and biomarker expression.

Extraocular seeding of choroidal melanoma after a transretinal biopsy with a 25-gauge vitrector.

Purpose: To report an isolated case of extraocular seeding of choroidal melanoma after a transretinal biopsy.

Methods: A 74-year-old man with a choroidal melanoma in the left eye underwent a 3-port transconjunctival 25-gauge transretinal biopsy (for cytogenetic prognostication) followed by proton beam radiotherapy. Biopsy showed the melanoma to be predominantly of spindle cell type with chromosome 3 loss.

Multiplex ligation-dependent probe amplification of conjunctival melanoma reveals common BRAF V600E gene mutation and gene copy number changes.

Purpose: To determine the occurrence of BRAF V600E gene mutations and copy number changes of all autosome arms and genes known to be frequently altered in tumorigenesis in primary and metastatic conjunctival melanomas (CoMs).

Methods: DNA (200 ng) was analyzed by three multiplex ligation-dependent probe amplification assays (P027 uveal melanoma, P036 human telomere, and P206 spitzoid melanoma).

Results: Eight of 16 primary tumor samples and 4 of 6 metastatic samples showed BRAF V600E gene mutations.