MDR1 EXPRESSION IS ASSOCIATED WITH ADVERSE SURVIVAL IN MELANOMA OF THE UVEAL TRACT

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 resistan ce in cancer cells, are expressed in ocular melanoma. Overexpression o f MDR1 has been associated with a poor survival in some tumor types tr eated by chemotherapy and in some untreated tumours. To assess whether MDR1 expression is of prognostic value in uveal melanoma, we evaluate d the expression of MDR1 by immunohistochemistry in 108 cases. Three s emiquantitative grades were used to evaluate positive staining. We det ected MDR1 expression in 80% of cases; 28% showed grade I staining; 30 %, grade II staining; and 22%, grade III staining There was a statisti cally significant association (P = .004) between MDR1 expression by tu mor 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 surviva l. We conclude that (1) MDR1 may be involved in chemoresistance and tu mor propagation in primary uveal melanoma, and (2) increasing levels o f expression are prognostically significant and may prove a useful mar ker of tumor invasiveness, independent of established prognostic facto rs. HUM PATHOL 29:594-598. Copyright (C) 1998 by W.B. Saunders Company .