epidermal-growth-factor and Uveal-Neoplasms

Uveal melanoma (UM) is the major intraocular malignancy in adults, of which the molecular biology is still unknown. Therefore, this study was designed to determine the aqueous concentrations of angiogenic, inflammatory, and chemotactic cytokines in eyes with UM.Aqueous humor samples were collected from 38 patients with UM and 22 patients undergoing cataract surgery. Interleukin 6, 8 (IL-6, IL-8, respectively), interferon-inducible protein-10 (IP-10), placental growth factor1 (PIGF1), regulated on activation, normal T Cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor-beta (NGF-β), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and vascular endothelia growth factor A (VEGF-A) were assessed by multiplex bead assay.In the study group, significantly higher concentrations of IL-6 (P = .006), IL-8 (P = .018), IP-10 (P = .004), RANTES (P = .008), MCP-1 (P = .02), NGF-β (P = .013), EGF (P < .001), PIGF1 (P = .01), bFGF (P = .016), and VEGF (P = .017) were measured, when compared with the control group.Several angiogenic, inflammatory, and chemotactic cytokines are highly expressed in the aqueous humor of the UM eyes, which provides new insights into the pathophysiology of UM and could be potential targets for treatment.

Topics: Adult; Aged; Aqueous Humor; Biomarkers, Tumor; Cataract Extraction; Cytokines; Epidermal Growth Factor; Female; Humans; Inflammation Mediators; Male; Melanoma; Middle Aged; Uveal Neoplasms; Vascular Endothelial Growth Factor A

Human Cripto, the founder member of the epidermal growth factor-Cripto-FRL1-Cryptic (EGF-CFC) family, plays an important role during early embryonic development and in particular in carcinogenesis and the development of cancer metastases. Cripto-1 is over-expressed in most cancers, but is absent or only weakly expressed in normal cells. For this reason, Cripto-1 could be of potential value in the targeted treatment. There is no information on the expression of Cripto-1 in human uveal melanoma. Cripto-1 reactivity was evaluated by immunohistochemistry on 36 archival uveal melanomas using the polyclonal antibody to Cripto-1. The tumors were divided in to 2 groups. There were 18 uveal melanomas with no intrascleral or extrascleral extension and 18 uveal melanomas with intrascleral/extrascleral extension/liver metastasis. Cripto-1 reactivity was correlated with tumor aggressiveness and cell type. Furthermore, we studied the immunolocalization of Cripto-1 in 4 uveal melanoma cell lines OCM-1, OCM-8, and 92-1, and OMM-1 and in 2 primary uveal melanocyte cultures. Cripto-1 was expressed in both the non-invasive and aggressive uveal melanomas. Cripto-1 was positive in the 4 uveal melanoma cell lines and absent in the primary uveal melanocyte cultures. Retinal tissue did not express Cripto-1. The results suggest that Cripto-1 is expressed in uveal melanoma, negative in the non-neoplastic ocular tissue and point to its use as a target for therapy.

Topics: Adult; Aged; Biomarkers, Tumor; Epidermal Growth Factor; Eye; Female; GPI-Linked Proteins; Humans; Immunoenzyme Techniques; Intercellular Signaling Peptides and Proteins; Liver Neoplasms; Male; Melanocytes; Melanoma; Membrane Glycoproteins; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins; Sclera; Tumor Cells, Cultured; Uveal Neoplasms

The immunoreactivity of epidermal growth factor receptor (EGFR) ezrin, hepatocyte growth factor receptor (HGF), and c-Met was studied in 60 uveal melanomas and was correlated with clinicopathologic parameters. Metastases were diagnosed in the patients with uveal melanoma between 5 years and 8 years (median, 6.5 years) after enucleation. Using Kaplan-Meier statistical analysis, we found a significant association between high c-Met expression and death due to uveal melanoma (p < 0.03). EGFR was expressed in 18 of 60 (30%) tumors; ezrin was expressed in 30 of 60 (50%) tumors. Tumors with liver metastasis (n = 6) showed higher expression of c-Met (p = 0.0009) compared with the tumors with no extension/extrascleral extension without liver metastasis (groups A-45 and B-9). HGF was negative in all the six tumors that had liver metastasis. Further studies are required to understand the possible mechanism of ligand-independent c-Met activation in patients with uveal melanoma.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Child; Cytoskeletal Proteins; Epidermal Growth Factor; Female; Hepatocyte Growth Factor; Humans; Immunoenzyme Techniques; Liver Neoplasms; Lymphocytes, Tumor-Infiltrating; Male; Melanoma; Middle Aged; Proto-Oncogene Proteins c-met; Survival Rate; Uveal Neoplasms