The role of c-kit and imatinib mesylate in uveal melanoma

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular tumor in adults, leading to metastasis in 40% of the cases and ultimately to death in 10 years, despite local and/or systemic treatment. The c-kit protein (CD117) is a membrane-bound tyrosine kinase receptor and its overexpression has been observed in several neoplasms. Imatinib mesylate is a FDA approved compound that inhibits tyrosine quinase receptors, as well as c-kit. Imatinib mesylate controls tumor growth in up to 85% of advanced gastrointestinal stromal tumors, a neoplasia resistant to conventional therapy. METHODS: Fifty-five specimens of primary UM selected from the archives of the Ocular Pathology Laboratory, McGill University, Montreal, Canada, were immunostained for c-kit. All cells displaying distinct immunoreactivity were considered positive. Four human UM cell lines and 1 human uveal transformed melanocyte cell line were tested for in vitro proliferation Assays (TOX-6) and invasion assay with imatinib mesylate (concentration of 10 μM). RESULTS: The c-kit expression was positive in 78.2% of the UM. There was a statistical significant decrease in the proliferation and invasion rates of all 5 cell lines. CONCLUSION: The majority of UM expressed c-kit, and imatinib mesylate does decrease the proliferation and invasion rates of human UM cell lines. These results justify the need for a clinical trial to investigate in vivo the response of UM to imatinib mesylate

Malignancy in the blind painful eye - report of two cases and literature review

Background: Few cases of malignant tumors arising in a blind painful eye have previously been described. We described two cases of a blind painful eye containing an unsuspected tumor, which were enucleated to relieve the pain.Case presentations: Case 1: A 57 year-old Caucasian man presented with recurrent orbital cellulitis and endophthalmitis in the left eye (OS). the OS was blind and painful and an enucleation was performed showing a uveal melanoma by histopathological exam. Case 2: A 54 year-old Caucasian man with previous history of a rhegmatogenous retinal detachment in his left eye presented a blind painful eye. Enucleation was performed revealing a well-differentiated B-cell lymphoma of uveal tract with extra ocular extension.Conclusion: in the management of a blind painful eye, it is extremely important to rule out an intraocular malignancy particularly in those patients who have not been followed by an ophthalmologist.Universidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilMcGill Univ, Dept Ophthalmol, Henry C Witelson Ocular Pathol Lab, Montreal, PQ H3A 2T5, CanadaPathol & Cytopathol Lab, LAC, Campo Grande, MS, BrazilUniv Desenvolvimento Estado & Regiao Pantanal, Campo Grande, MS, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc

Prostate-specific membrane antigen is undetectable in choroidal neovascular membrane

BACKGROUND: Choroidal neovascular membrane (CNVM) is one of the leading causes of severe visual loss and is often associated with age-related macular degeneration (AMD). Various modalities of treatment, including photocoagulation and surgery, are being considered as options, but with limited success. Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein expressed in benign and malignant prostatic tissues, in some non-prostatic tissues, and in the endothelium of tumor-associated neovasculature of non-prostatic neoplasm. Some studies have suggested that the expression of PSMA is restricted to endothelium from tumor-associated neovasculature and might be stimulated by some tumor-secreted angiogenic factors. However, no previous study demonstrating PSMA expression in non-related tumor neovasculature, such as CNVM, has been performed to date. Furthermore, demonstration of PSMA expression in CNVM in AMD patients could reveal a novel target for antineovascular therapy. The purpose of this study was to evaluate the immunohistochemical expression of PSMA in CNVM from AMD. METHODS: Immunohistochemical analysis, with a standard avidin-biotin complex technique, was performed using an anti-PSMA mouse monoclonal antibody in 30 specimens of surgically excised CNVM from AMD patients. Antibody to an endothelial cell specific marker, factor VIII, was used to confirm the location of the endothelial cells. RESULTS: The angiogenic microvessels of the 30 cases demonstrated negative staining to PSMA while factor VIII was expressed in all cases. Seventy-five percent of the secretory-acinar epithelium of the prostatic hyperplasia specimen stained positive, confirming that the immunohistochemical technique was correctly performed. CONCLUSION: The absence of PSMA expression in non-tumoral neovasculature supports the theory, previously suggested, that endothelial cell PSMA expression may be stimulated by one or more tumor-secreted angiogenic factors. Angiogenesis is very important in neoplasia and the endothelial expression of PSMA in tumor-associated neovasculature may represent a target for antineovasculature-based therapy. The absence of PSMA expression in CNVM suggests that PSMA may not be a potential target for antineovasculature-based therapy

Cytokeratin expression in corneal dystrophies

PURPOSE: To identify an immunohistochemical pattern of epithelial markers in granular, lattice and Avellino corneal dystrophies. METHODS: Twenty-two corneal buttons, diagnosed as lattice (17), Avellino (4) and granular (1) underwent immunohistochemical studies of cytokeratins (CKs) on pa- raffin-embedded sections (group I). Monoclonal antibodies for pan-CK (AE1/AE3) and CKs 3/12, 5/6, 8, 18 and 19 were used. Twenty-two normal corneas were used as the control (group II). RESULTS: Six lattice and 2 Avellino cases of group I stained positively with anti-CK 3/12 in corneal epithelium and areas of corneal stroma deposits. One of these cases of lattice was positive for anti-pan-CK (AE1/AE3) also in the epithelium and areas of corneal stroma deposits with a similar pattern. None of the controls (group II) revealed any staining in corneal stroma. All disease and control cases (groups I and II) revealed positive staining in corneal epithelium. CONCLUSION: AE1/AE3 and CK 3/12 anti-CK positive markers in the stromal deposits of lattice and Avellino dystrophies may suggest an epithelial genesis of the disease

Negative hybrid capture in a single intraepithelial corneal dysplasia

As displasias intraepiteliais de córnea correspondem a lesões de baixo risco de malignidade, dentro do espectro das neoplasias intraepiteliais da superfície ocular. Essas displasias se apresentam como áreas leucoplásicas e têm como um dos principais fatores de risco o papilomavírus humano (HPV). No presente trabalho, os autores descrevem um caso de displasia intraepitelial isolada de córnea, tratada através de excisão cirúrgica, com confirmação histológica e resultado negativo de hibridização de DNA para HPV.Cornea intraepithelial dysplasias are lesions with low risk of malignancy within the spectrum of intraepithelial neoplasia of the ocular surface. These areas are presented as dysplasias or leukoplasias and are associated with the presence of human papillomavirus (HPV), a major risk factor. In this report, the authors describe a case of a corneal intraepithelial dysplasia treated by surgical excision, with histological confirmation and negative DNA hybridization for HPV