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C. Eberhart, R. Bell, M. Coonfield, A. Spitze; Twist, E-cadherin and Uveal Melanoma Metastasis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3396.
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Metastatic spread is the main cause of death in patients suffering from uveal melanomas, but the molecular basis of tumor dissemination is only partially understood. Increased expression of proteins linked to epithelial mesenchymal transition (EMT) have been previously associated with invasion and metastasis in a number of cancers, but they have not been analyzed in uveal melanoma. We therefore examined expression of the EMT-associated protein Twist in uveal melanoma cell lines and in primary tumors. We also analyzed E-cadherin, which is frequently downregulated by Twist in metastatic carcinomas.
Twist expression was analyzed using Western blots of protein extracts from four uveal melanoma cell lines (OCM1, OMM1, OM431, MEL290), and by immunohistochemical analysis of a tissue microarray containing representative cores from 80 uveal melanomas. At least three intact cores were required for a tumor to be scored. We also examined E-cadherin levels using immunohistochemistry on the tissue microarray. A semiquantitative (0, 1+, 2+, 3+) scale was utilized for the immunohistochemical evaluations.
Twist was detected in protein extracts from all four uveal melanoma cell lines examined. On the tissue array, 72 cases had sufficient evaluable cores for analysis, and 27 of these (38%) had high levels (3+) of Twist. In the same 72 tumors, 18 (25%) had very low or absent (0 to 1+) expression of E-cadherin. Interestingly, 11 of the 18 tumors (61%) with low or absent E-cadherin had high levels of Twist, suggesting that Twist might repress E-cadherin expression in uveal melanoma. Statistical analysis of the immunohistochemical staining data in all 72 cases showed a trend towards a negative correlation between Twist and E-cadherin (p = 0.06, two-tailed Spearman test).
High levels of Twist protein expression are more common in uveal melanoma with low E-cadherin, suggesting a potential relationship between the two, although the overall negative correlation is not statistically significant (p = 0.06). Clinical data are being collected for the patients whose tumors were included on our tissue array, and an analysis of the association between Twist, E-cadherin and metastasis is planned.
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