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K. D. Godeiro, E. Antecka, A. N. Odashiro, V. Saraiva, J. C. Marshall, M. N. Burnier, Jr.; Immunohistochemical Expression of Nuclear Factor-kB in Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4778.
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Uveal melanoma (UM) is the most common primary intra-ocular malignancy in adults. Despite the high accuracy of clinical diagnosis and advances in the local treatment, more than 40% of UM patients will develop metastases that ultimately lead to death. Therefore, the search for new treatment strategies is necessary. The nuclear factor-kappa B (NF-ΚB) is a dimeric transcription factor, which is related to carcinogenesis by regulating genes involved in apoptosis, cell cycle, differentiation and migration. Although the role of NF-ΚB in protecting skin melanoma cells from apoptosis has received considerable interest recently, its expression in UM has not been studied yet. Therefore, the purpose of this study is to describe NF-ΚB expression in UM and to evaluate its possible association with clinicopathological features.
The patient’s medical charts were reviewed to provide the following information: age at date of diagnosis, gender, previous ocular radiation therapy, development of distant metastasis and date of last medical consultation with clinical status. Histopathologic analysis of the specimens with regards to prognostic factors such as cell type, largest tumor dimension, and tumor-infiltrating lymphocytes was performed. Thirty-tree UM specimens were subjected to immunohistochemical analysis with anti- NF-ΚB monoclonal antibody. Samples were classified as low (+1), moderate (+2) or high (+3) positivity regarding to quantity and intensity of staining. The final microscopic classification was defined as high (group 1) if the combination of both quantity and intensity of staining was ≥ +5, and low (group 2) if this combination was < +5.
All cases subjected to immunohistochemistry were found to be NF-ΚB positive. 66.6% (n = 22) presented high cytoplasmatic and nuclear immunoreactivity. Meanwhile, among lesions with low immunoreactivity (n = 11), 100% presented with cytoplasmatic reaction with no nuclear staining. Although statistical analysis demonstrated no correlation between NF-ΚB expression and histopathologic and clinical prognostic factors, interestingly, patients that presented with high expression of NF-ΚB had a higher cumulative metastasis rate than those from group 2.
The results of this study demonstrated that NF-ΚB is highly expressed in UM. Recent advances in the development of drugs that down-regulate NF-ΚB signaling may therefore provide potential adjuvant to conventional therapies in UM.
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