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S.C. Maloney, S. Bakalian, A.B. T. Dias, K.D. Godeiro, E. Antecka, M.N. Burnier, Jr.; Expression of Cytokeratins 8 and 18 in Human Melanoma Cells Obtained From a Rabbit Model of Uveal and Cutaneous Melanoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2231.
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Cytokeratins (CK) 8 and 18 are ubiquitously expressed in normal and cancerous epithelial cells and are among the most abundant cytokeratins in these cell types. As such, they are useful immunohistochemical markers in the identification of epithelial malignancies. The purpose of this study was to analyze the expression of CK 8 and 18 in melanoma cells of intraocular tumor, lung metastases, and bone marrow derived malignant cell (BMMC) samples obtained from a rabbit model of uveal and cutaneous melanoma.
Immunohistochemistry was used to quantify the expression of both CK 8 and 18 in paraffin–embedded sections of primary tumors and lung metastases, as well as in BMMC cytospins, isolated from 4 rabbits of an animal model of uveal and cutaneous melanoma. Two of these rabbits (Group A) had initially received an intraocular injection of human cutaneous melanoma cells while the remaining two (Group B) had been injected with a human uveal melanoma cell line. All rabbits developed primary intraocular tumors along with lung metastases. At the time of sacrifice, bone marrow was taken and malignant cells were cultured. Analyses of CK 8 and 18 expression were performed by two independent investigators and no discrepancies were found.
Comparison of immune expression in primary tumors demonstrated that positive staining for CK 18 is always equivalent to or greater than CK 8, with no significant difference between Group A and Group B. Analysis of BMMC cytospins showed extensive expression of CK 8 and 18 in both groups. There was greater expression of CK 18 than CK 8 in the lung samples of all rabbits in both groups.
This study confirms previous results obtained from genetic analysis of an up–regulation of CK 18 in intraocular tumors and metastasis in both cutaneous and uveal melanoma. Moreover the down–regulation of CK 8 from bone marrow derived malignant cells to metastases indicates that CK 8 may play an important role in the ability of melanoma cells to circulate in the blood stream and survive in the bone marrow.
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