Aberrant survivin expression in endometrial hyperplasia: Another mechanism of progestin resistance

Xiaojun Chen, Zhenbo Zhang, Youji Feng, Oluwole Fadare, Jun Wang, Zhihong Ai, Hongyan Jin, Chao Gu, Wenxin Zheng

Research output: Contribution to journalArticle

26 Scopus citations

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 μM 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.

Original languageEnglish (US)
Pages (from-to)699-708
Number of pages10
JournalModern Pathology
Volume22
Issue number5
DOIs
StatePublished - May 1 2009

Keywords

  • Endometrial cancer
  • Endometrial hyperplasia
  • Progestin
  • Progestin resistance
  • Survivin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Aberrant survivin expression in endometrial hyperplasia: Another mechanism of progestin resistance'. Together they form a unique fingerprint.

  • Cite this