Abstract
Up to 30% of failure rate in endometrial hyperplasia patients treated by progestin urges more detailed understanding of the mechanisms involved in progestin resistance. Survivin is a key regulator in the antiapoptotic network, and overexpression of survivin has been reported in endometrial hyperplasia and cancer. This study investigated the role of survivin in progestin resistance in endometrial hyperplasia. Pre- and post-treatment endometrial hyperplasia tissue samples from 23 women were examined for changes in survivin expression related to the administration of progestins. The impact of continuous or intermittent progestin treatment on survivin expression in Ishikawa cells was examined by the western blot. Survivin immunoreactivity was present in epithelial compartment of all pre-progestin-treated endometrial hyperplasia samples with mean nuclear indices 78 and cytoplasmic indices 114. In the 15 progestin responders, an average of 19.5-fold decrease of survivin expression was seen in epithelial nuclei (P<0.001) and 8-fold decrease in epithelial cytoplasm (P<0.001). In the eight non-responders, no significant changes in survivin expression were detected. With in vitro Ishikawa cells, survivin expression was effectively inhibited by either 72-h continuous treatment with 10 muM medroxyprogesterone acetate or 72 h after medroxyprogesterone acetate withdrawal. Our results indicated that dysregulation of survivin expression in hyperplastic endometrium may be part of the molecular mechanisms for progestin resistance. Intermittent, rather than continuous, progestin treatment may be more effective clinically for the treatment of endometrial hyperplasia.