MDR1 expression is associated with adverse survival in melanoma of the uveal tract

Human Pathology
B M DunneS M Kennedy

Abstract

Metastatic uveal melanoma is profoundly chemoresistant and has a very poor outcome. We have previously shown that the MDR1 gene and its gene product P-glycoprotein (P-gp), which are known to cause drug resistance in cancer cells, are expressed in ocular melanoma. Overexpression of MDR1 has been associated with a poor survival in some tumor types treated by chemotherapy and in some untreated tumours. To assess whether MDR1 expression is of prognostic value in uveal melanoma, we evaluated the expression of MDR1 by immunohistochemistry in 108 cases. Three semiquantitative grades were used to evaluate positive staining. We detected MDR1 expression in 80% of cases; 28% showed grade I staining; 30%, grade II staining; and 22%, grade III staining. There was a statistically significant association (P=.004) between MDR1 expression by tumor cells and shorter survival times (n=96), which was most striking at grade III levels of expression. Multivariate analysis showed that MDR1 expression is an independent prognostic indicator of poor survival. We conclude that (1) MDR1 may be involved in chemoresistance and tumor propagation in primary uveal melanoma, and (2) increasing levels of expression are prognostically significant and may prove a ...Continue Reading

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Citations

Dec 4, 2004·Melanoma Research·Martin Schmidt-HieberUlrich Keilholz
Jan 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Andre LevchenkoSteven M Larson
Jun 4, 2005·Clinical & Experimental Ophthalmology·João P Souza FilhoMiguel N Burnier
May 18, 2011·Pigment Cell & Melanoma Research·Solange LandrevilleJ William Harbour
Feb 14, 2002·The British Journal of Dermatology·M AmeenJ N W N Barker
Sep 4, 2009·Pigment Cell & Melanoma Research·Kevin G ChenMichael M Gottesman
Sep 6, 2005·Journal français d'ophtalmologie·J GambrelleL G Baggetto

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