mart-1-antigen and Choroid-Neoplasms

To determine the ocular safety of CP-675,206 (Pfizer, New York, New York, USA), a fully human anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody in clinical trials of immunotherapy of metastatic melanoma.. Prospective, nonrandomized study of the eye and vision in phase I/II clinical trials of CP-675,206 in metastatic melanoma conducted at the University of California, Los Angeles.. Patients with regional or distant metastatic melanoma were enrolled in phase I/II clinical trials evaluating the safety and antitumor efficacy of CP-675,206 alone or in combination with melanoma antigen peptide-pulsed dendritic cell vaccines. Ophthalmic evaluation was performed at the onset of CP-675,206 immunotherapy (baseline evaluation), two months or more after the onset of CP-675,206 immunotherapy (end-study evaluation), and at two- to three-month intervals thereafter in patients who continued to receive CP-675,206 immunotherapy (poststudy evaluation). Baseline and end-study evaluations included comprehensive ophthalmic examination, psychophysical and electrophysiologic visual function assessment, fundus photography, fluorescein angiography, and visual function assessment.. Twenty patients with metastatic melanoma arising from the skin, mucosa, eye, or unknown site were evaluated. Systemic toxicity attributed to CP-675,206 included dermatologic manifestations, diarrhea, and autoimmune hepatitis with panhypopituitarism. A subset of patients receiving CP-675,206 demonstrated antitumor efficacy with partial response or complete response of metastatic melanoma. Comparison of ophthalmic baseline with end-study evaluations in all 20 patients and limited-term poststudy evaluations showed no adverse effect of CP-675,206 immunotherapy on the eye or vision.. In this study, CP-675,206 immunotherapy for metastatic melanoma did not adversely affect the eye or vision.

Topics: Abatacept; Adult; Aged; Aged, 80 and over; Antibodies, Blocking; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antigens, Neoplasm; Anus Neoplasms; Choroid Neoplasms; Drug Therapy, Combination; Electrooculography; Electroretinography; Female; Fluorescein Angiography; Humans; Immunoconjugates; Immunotherapy; Male; MART-1 Antigen; Melanoma; Middle Aged; Neoplasm Proteins; Neoplasms; Ocular Physiological Phenomena; Prospective Studies; Skin Neoplasms; Treatment Outcome; Vision, Ocular; Visual Acuity

To report a previously unrecognized choroidal melanoma clinical feature termed tumor-associated retinal pigmentation (TARP) and determine any correlation with tumor biology.. Imaging and histologic analysis of a retrospective cohort of patients.. Patients with choroidal melanoma identified as having TARP on funduscopy at the Liverpool Ocular Oncology Centre (LOOC), United Kingdom, from January 2020 through January 2023.. Clinical and imaging characteristics of patients diagnosed with choroidal melanoma and exhibiting TARP on fundoscopy were documented. Details of these choroidal melanomas were collated and correlated with histopathology and molecular genetic reports. The chromosome 3 status of each tumor was assessed. In enucleated samples, immunostaining was undertaken to determine the nature of the TARP using specific markers (CD68 and MelanA).. Features of TARP on widefield fundus color imaging, fundus autofluorescence (FAF), and OCT were described. Tumor chromosome 3 status and the immunoprofile of the TARP also were collated.. Tumor-associated retinal pigmentation had a prevalence rate of 7.47 per 100 cases of choroidal melanoma at the LOOC. Twenty-three eyes with TARP were analyzed, with a mean age of 71.4 years (range, 51-88 years). The median largest basal diameter was 16.10 mm (range, 9.17-21.32 mm), and the mean tumor thickness was 8.04 mm (range, 1.40-13.80 mm). Tumor-associated retinal pigmentation was observed on widefield color fundus imaging, with hypofluorescence on FAF images and represented hyperreflective foci located in intraretinal and subretinal spaces on OCT scans. Seventeen patients (73.9%) underwent enucleation, and 6 patients (26.1%) underwent globe-sparing treatment. Molecular genetic analysis of 20 choroidal melanomas (after enucleation or radiotherapy biopsy) revealed monosomy 3 in 18 tumors (90%). Immunostaining of the TARP in enucleated eyes showed CD68+ melanophages in all 17 patients appearing as scattered cells and aggregates; MelanA findings were negative.. Tumor-associated retinal pigmentation represents tumor-associated macrophages, not melanocytes, within intraretinal and subretinal spaces of larger choroidal melanomas. Radiation treatments need not involve this area in the treatment plan, minimizing radiation-related complications. This novel clinical sign seems to be linked to tumors of high metastatic-risk clinical and genetic characteristics, with a preponderance having monosomy 3 anomalies.. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Topics: Aged; Choroid Neoplasms; Fluorescein Angiography; Humans; MART-1 Antigen; Melanoma; Monosomy; Pigmentation; Retrospective Studies

Although rare, uveal melanoma (UM) is the most common primary intraocular tumor in adults. About half of UM patients develop metastatic disease typically in the liver and die within a short period, due to ineffective systemic therapies. UM has unique and distinct genetic features predictive of metastasis. Animal models are required to improve our understanding of therapeutic options in disseminated UM. Since spontaneous murine UM models are lacking, our aim was to analyze the suitability of the established transgenic melanoma mouse model Tg(Grm1) as a new UM model system. We demonstrated that adult Grm1 transgenic mice develop choroidal thickening and uveal melanocytic neoplasia with expression of the melanocytic markers S100B and MelanA. Further, we showed that GRM1 is expressed in human UM, similar to skin melanoma. This study presents a new mouse model for spontaneous UM and suggests that the glutamate signaling pathway is a possible target for UM therapy.

Topics: Animals; Biomarkers, Tumor; Choroid; Choroid Neoplasms; Disease Models, Animal; Fluorescent Antibody Technique, Indirect; Ki-67 Antigen; MART-1 Antigen; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, Transgenic; Real-Time Polymerase Chain Reaction; Receptors, Metabotropic Glutamate; RNA, Messenger; S100 Calcium Binding Protein beta Subunit; Skin Neoplasms; Tumor Cells, Cultured

Topics: Animals; Antigens, Neoplasm; Biomarkers, Tumor; Choroid Neoplasms; Female; Fluorescein Angiography; Macaca fascicularis; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Monkey Diseases; Neoplasm Proteins; Tomography, Optical Coherence; Ultrasonography

To determine the immunophenotypic differences between uveal and cutaneous melanomas, employing standard melanoma markers as well as p75 neurotrophin receptor (p75NTR) and microphthalmia transcription factor (MITF).. Fifteen uveal melanomas (5 spindle, 5 epithelioid, and 5 mixed uveal subtypes) were immunolabeled with a panel of antibodies that included S100, tyrosinase, melan-A, HMB-45 and HMB-50 combination, MITF, and p75NTR. The results were tabulated on the basis of intensity and pervasiveness of the labeling and compared with a prior study on cutaneous spindle and epithelioid melanomas.. In contrast to its strong labeling of cutaneous melanomas, S100 immunolabeling of uveal melanomas was weak and variable. p75NTR, known to differentiate spindle from epithelioid melanomas of the skin, did not immunolabel uveal melanomas. HMB-45, HMB-50, tyrosinase, melan-A, and MITF immunolabeled all uveal melanomas strongly, irrespective of the histologic subtype, but not cutaneous melanomas. Microphthalmia transcription factor was especially clear in its labeling of uveal melanomas.. Although cutaneous and uveal melanomas share many molecular markers in common, there are differences between the 2 types of melanoma. First, the level of expression of S100 differs between cutaneous and uveal melanomas. Second, while cutaneous melanomas can be further subdivided into spindle and epithelioid types based on their immunophenotype, the uveal melanomas cannot.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Choroid Neoplasms; DNA-Binding Proteins; Humans; Immunophenotyping; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Neoplasm Proteins; Receptor, Nerve Growth Factor; Receptors, Nerve Growth Factor; S100 Proteins; Skin Neoplasms; Transcription Factors

Schwannoma (neurilemoma) arising from the ciliary body and choroid is a rare form of intraocular tumor and usually misdiagnosed clinically as amelanotic melanoma. This case report describes a 73-year-old woman who developed a large nonpigmented intraocular tumor of the choroid in the left eye and underwent enucleation with a clinical diagnosis of malignant melanoma. The tumor consisted of spindle-shaped cells with an indefinite cytoplasm and twisted nuclei, which had positive immunoreactivity for S-100 protein, vimentin, glial fibrillary acidic protein and neural cell adhesion molecule. A continuous basal lamina encompassing the tumor cells was demonstrated by immunostaining for laminin and type IV collagen. Ultrastructurally, tumor cells with scant organelles had delicate cytoplasmic processes apposing each other, all indicative of Schwann cell origin. In reexamination of fluorescein angiograms, ultrasonograms and magnetic resonance images, no findings were incompatible with a diagnosis of choroidal melanoma. Histopathological studies showed that the tumor was a schwannoma. At present, we do not have a benchmark for the clinical diagnosis of intraocular schwannoma.

Topics: Actins; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Choroid Neoplasms; Diagnosis, Differential; Eye Enucleation; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; MART-1 Antigen; Neoplasm Proteins; Neural Cell Adhesion Molecules; Neurilemmoma; S100 Proteins

A 47-year-old woman developed metastatic melanoma to the right ovary 14 years after the enucleation of the right eye for a choroidal spindle cell melanoma. An immunohistochemical study was performed on paraffin sections of both primary and metastatic melanoma specimens to identify markers of both aggressive phenotype and metastatic potential with particular attention to the anomalous expression of cytokeratin intermediate filament proteins. Neoplastic cells of both primary and metastatic tumors immunostained positively for S-100, HMB45, MART-1, and vimentin antibodies, but they were negative for cytokeratins 1-19, 8, 18, and 8,18; <10% of neoplastic cells in both the primary and the metastatic melanomas immunostained for Ki-67 proliferating antigen using MIB-1 antibody. We speculate that the indolent behavior of this ovarian metastasis is reflected by the absence of coexpression of cytokeratins 8 and 18 with vimentin. This case supports the practical value of using this panel of antibodies to evaluate the aggressive potential of uveal melanomas.

Topics: Antigens, Neoplasm; Carcinoma; Choroid Neoplasms; Female; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratins; Ki-67 Antigen; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Ovarian Neoplasms; S100 Proteins; Time Factors; Vimentin

Topics: Alleles; Amino Acid Sequence; Antigens, Neoplasm; Choroid Neoplasms; Ciliary Body; Eye Neoplasms; gp100 Melanoma Antigen; HLA-A Antigens; Humans; MART-1 Antigen; Melanoma; Membrane Glycoproteins; Monophenol Monooxygenase; Neoplasm Proteins; Peptide Fragments; T-Lymphocytes, Cytotoxic