Comparison of estrogen receptor-α, progesterone receptor and calponin expression in gonadotrophin-releasing hormone agonist-sensitive and -resistant uterine fibroids

Abstract

ObjectiveThis study was aimed to compare immunohistochemical expression of estrogen receptor (ER)-α, progesterone receptor (PR), and calponin in gonadotrophin-releasing hormone agonist (GnRH-a)-sensitive and -resistant uterine fibroids.MethodsWe collected data retrospectively. The sensitive group consisted of women who had reduction in uterine volume greater than 40% following GnRH-a treatment. Uterine volume was either reduced by less than 10%, or was increased in the resistant group. A tissue microarray was constructed using formalin-fixed, paraffin-embedded tissues, 31 and 26 patients for the sensitive and resistant groups, respectively. Tissue sections were immunostained with antibodies against ER-α, PR, and calponin. The intensity and area of the immunohistochemical reactions were evaluated using a semi-quantitative scoring system. The Mann-Whitney U-test, Fisher's exact test, and Spearman's rank correlation test were used for analysis of data.ResultsPR (P = 0.04) and calponin (P = 0.03) showed a significantly higher staining intensity in the resistant group than in the sensitive group. Both groups showed comparable expression of ER-α (P = 0.23). In correlation analysis between changes in uterine volume after GnRH-a therapy and clinicopathological factors, the immunohistochemical intensity of PR (P = 0.04) and calponin (P = 0.03) was significantly correlated with changes in uterine volume.ConclusionThis study shows that GnRH-a resistance of uterine fibroids is not related to ER-α content, but the expression of PR and calponin is related with GnRH-a resistance.

Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth

“…These findings suggest that estrogens exert their pro-mitogenic effect by transcriptional mechanisms (Andersen et al, 1995;Pedeutour et al, 1998;Yin et al, 2007). There seems to be no difference in estrogen receptor-a (ERa) expression in GnRH agonist-sensitive and -resistant uterine fibroids (Kim et al, 2014). Proliferation of Eker rat-derived leiomyoma cell lines, which carry a germline mutation in the Tsc2 gene, is also stimulated by 17b-estradiol and inhibited by the selective estrogen receptor modulator (SERM) tamoxifen in vitro (Howe et al, 1995).…”

Down-regulation and gene hypermethylation of the 14-3-3 gamma in uterine leiomyoma

“…Uterine leiomyoma increases the risk of abnormal bleeding, infertility, and pregnancy complications (16). It is generally accepted that this is a hormone-dependent disease, and that estrogen and progesterone greatly influence its development (17)(18)(19) through the activation of ER and PR, respectively. Previous studies indicated that ER-alpha and ER-beta might play different roles in the proliferation of uterine leiomyoma cells.…”