Effect of asoprisnil on uterine proliferation markers and endometrial expression of the tumour suppressor gene, PTEN

J Wilkens, A R W Williams, K Chwalisz, C Han, I T Cameron, H O D Critchley

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND The selective progesterone receptor modulator asoprisnil suppresses uterine bleeding and decreases leiomyoma volume while maintaining follicular phase estrogen concentrations. For safety of potential clinical applications, any proliferative effect of asoprisnil on uterine tissues, particularly endometrium, needs to be established.

METHODS In a double-blind, randomized, placebo-controlled study (continuation of previously published trial No. NCT00150644 (Williams et al., 2007 and Wilkens et al., 2008)), 33 patients with symptomatic uterine leiomyomata received placebo, 10 or 25 mg asoprisnil daily for 12 weeks before hysterectomy. Proliferation markers Ki-67 and anti-phospho-histone H3 (PH3) were immunolocalized in endometrium, myometrium and leiomyoma tissue. Endometrial PTEN (phosphatase and tensin homologue, a tumour suppressor gene) expression was also assessed by immunohistochemistry. PH3-positive glandular and stromal cells were counted per measured endometrial area. Endometrial Ki-67 expression was assessed using stereological methods. Stained myometrial and leiomyoma cells were counted per 10 fields (×250). PTEN immunostaining was quantified using a histoscore. Each asoprisnil group was compared with placebo (secretory phase) with significance at 0.05 level.

RESULTS Endometrial epithelial proliferation and PTEN expression were not significantly different between placebo and asoprisnil groups. Decreased stromal Ki-67 expression (P < 0.05) suggested any effect of asoprisnil on endometrial proliferation to be inhibitory. Immunolocalization of PTEN expression was not different between treatment groups in any tissue compartments. Myometrial Ki-67 expression decreased following asoprisnil 25 mg (P < 0.05).

CONCLUSIONS Asoprisnil does not induce proliferation of uterine tissues and does not suppress endometrial PTEN expression.
Original languageEnglish
Pages (from-to)1036-1044
Number of pages9
JournalHuman Reproduction
Volume24
Issue number5
DOIs
Publication statusPublished - May 2009

Keywords

  • asoprisnil
  • uterine tissues
  • proliferation
  • phosphatase and tensin homologue

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