Effect of asoprisnil on uterine proliferation markers and endometrial expression of the tumour suppressor gene, PTEN.
Effect of asoprisnil on uterine proliferation markers and endometrial expression of the tumour suppressor gene, PTEN.
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 [ClinicalTrials.gov] (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 (x250). 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.
asoprisnil, uterine tissues, proliferation, phosphatase, tensin homologue
1036-1044
Wilkens, J.
7061cca5-5e9c-47de-88ed-aa7262475e01
Williams, A.R.W.
973ff46f-46f1-4d7c-b27d-0f53221e4c44
Chwalisz, K.
49b9ee58-ab3a-441c-92d5-22e4320d02aa
Han, C.
fd5b11fe-fccf-4e00-ad20-9d1a4e528f1a
Cameron, I.T.
f7595539-efa6-4687-b161-e1e93ff710f2
Critchley, H.O.D.
4b7fb4e8-0545-468a-88e0-ee3aa8efb81b
May 2009
Wilkens, J.
7061cca5-5e9c-47de-88ed-aa7262475e01
Williams, A.R.W.
973ff46f-46f1-4d7c-b27d-0f53221e4c44
Chwalisz, K.
49b9ee58-ab3a-441c-92d5-22e4320d02aa
Han, C.
fd5b11fe-fccf-4e00-ad20-9d1a4e528f1a
Cameron, I.T.
f7595539-efa6-4687-b161-e1e93ff710f2
Critchley, H.O.D.
4b7fb4e8-0545-468a-88e0-ee3aa8efb81b
Wilkens, J., Williams, A.R.W., Chwalisz, K., Han, C., Cameron, I.T. and Critchley, H.O.D.
(2009)
Effect of asoprisnil on uterine proliferation markers and endometrial expression of the tumour suppressor gene, PTEN.
Human Reproduction, 24 (5), .
(doi:10.1093/humrep/den494).
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 [ClinicalTrials.gov] (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 (x250). 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.
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Published date: May 2009
Keywords:
asoprisnil, uterine tissues, proliferation, phosphatase, tensin homologue
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Local EPrints ID: 155307
URI: http://eprints.soton.ac.uk/id/eprint/155307
PURE UUID: fe2af356-db20-4d04-bb9b-6d947df66001
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Date deposited: 28 May 2010 11:13
Last modified: 14 Mar 2024 02:42
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Author:
J. Wilkens
Author:
K. Chwalisz
Author:
C. Han
Author:
H.O.D. Critchley
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