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
References
Jan 24, 1992·Science·K V ChinM M Gottesman
Jan 16, 1991·Journal of the National Cancer Institute·P VerrelleJ Chassagne
Dec 5, 1991·The New England Journal of Medicine·H S ChanV Ling
Jan 1, 1991·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·C K van KalkenG Giaccone
Apr 1, 1990·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H S ChanV Ling
Nov 1, 1990·British Journal of Cancer·G C WishartS B Kaye
May 15, 1991·Journal of the National Cancer Institute·R PirkerL Havelec
Feb 1, 1989·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·F ThiebautM C Willingham
Oct 1, 1974·Cancer·L H EinhornJ A Gottlieb
Jul 15, 1983·Cancer·S RajpalC P Karakousis
Oct 1, 1983·American Journal of Ophthalmology·I W McLeanJ W Gamel
May 1, 1981·Southern Medical Journal·A Y BedikianG P Bodey
Apr 1, 1995·The British Journal of Dermatology·D SchadendorfB M Czarnetzki
Oct 1, 1993·Cancer·R KathS Seeber
Jun 1, 1993·The Journal of Surgical Research·E A LevineT K Das Gupta
Jan 1, 1995·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·G GiacconeH M Pinedo
Jun 1, 1996·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·L J Goldstein
Nov 1, 1996·The British Journal of Ophthalmology·M McNamaraS M Kennedy
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
Oct 26, 2016·Veterinary and Comparative Oncology·R FinotelloL Ressel
Nov 4, 2005·Proteomics·María PardoNicole Zitzmann
Oct 28, 2005·British Journal of Cancer·S HughesR S Houlston
Aug 2, 2007·Biological & Pharmaceutical Bulletin·Yuko TakebaShinichi Kobayashi
Sep 6, 2005·Journal français d'ophtalmologie·J GambrelleL G Baggetto