Baytur Yesim Bulbul, Ozbilgin Kemal, Cilaker Serap, Lacin Selman, Kurtul Ozgur, Oruc Semra, Koyuncu Faik Mumtaz
Celal Bayar University School of Medicine, Department of Obstetrics and Gynecology, Turkey.
Eur J Obstet Gynecol Reprod Biol. 2007 Nov;135(1):94-103. doi: 10.1016/j.ejogrb.2006.07.042. Epub 2006 Sep 14.
To compare the mechanism of action of raloxifene and gosereline induced shrinkage of leiomyomas via estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically.
Thirty-two premenopausal women affected by uterine leiomyomas were randomized into two equal groups. Group A was treated with gosereline (3.6 mg subcutaneous injection monthly) and group B was treated with raloxifene (60 mg daily per os) for 3 months before undergoing surgery. At entry and at the end of the treatment the leiomyoma volume was measured ultrasonografically and the volume change was calculated. Immunohistochemical detection of estrogen receptor (ER), progesterone receptor (PR), bcl-2 and p53 were performed on leiomyoma tissue samples from group A, group B and the matched-control group. H-scores for ER, PR, bcl-2 and p53 were calculated. The mean volume changes of leiomyomas and immunohistochemical H-score differences of ER, PR, bcl-2 and p53 were compared between groups.
The leiomyoma volume decreased significantly after treatment in gosereline group from baseline of 65 cm(3) to 35 cm(3), and in raloxifene group from 68 cm(3) to 50 cm(3), p<0.05. The difference between the before and after treatment leiomyoma volumes between the two treatments was not statistically significant. H-score of ER expression was significantly lower in gosereline group compared to control group (54.4 versus 113.2, p = 0.001), whereas H-score of PR expression was significantly lower with both gosereline and raloxifene groups compared to control group (64.8 for gosereline versus 94.6 for control, 73.6 for raloxifene versus 94.6 for control, p = 0.001). The bcl-2 expression was higher in both gosereline and raloxifene groups compared to control group (173.7 for gosereline versus 94.7 for control, 179.7 for raloxifene versus 94.7 for control, p = 0.001). The p53 expression was only lower with gosereline than the control group (169.4 versus 205.6, p = 0.001), whereas there was no significant change between the raloxifene group and the control group (201.9 versus 205.6) (p>0.05).
Raloxifene was as effective as gosereline in reducing leiomyoma volumes. Decreased PR expression may be a mechanism for tumor growth reduction in raloxifene treatment. In both treatment modalities, the mechanism of shrinkage of leiomyomas could not be increased apoptosis mediated by bcl-2 and p53 expression and should be investigated by further studies.
通过免疫组织化学法比较雷洛昔芬和戈舍瑞林通过雌激素受体、孕激素受体、bcl-2和p53表达诱导子宫肌瘤缩小的作用机制。
32例患有子宫肌瘤的绝经前妇女被随机分为两组。A组接受戈舍瑞林治疗（每月皮下注射3.6mg），B组在手术前3个月接受雷洛昔芬治疗（每日口服60mg）。在治疗开始时和结束时，通过超声测量子宫肌瘤体积并计算体积变化。对A组、B组和配对对照组的子宫肌瘤组织样本进行雌激素受体（ER）、孕激素受体（PR）、bcl-2和p53的免疫组织化学检测。计算ER、PR、bcl-2和p53的H评分。比较两组间子宫肌瘤的平均体积变化以及ER、PR、bcl-2和p53免疫组织化学H评分差异。
戈舍瑞林组治疗后子宫肌瘤体积从基线的65cm³显著降至35cm³，雷洛昔芬组从68cm³降至50cm³，p<0.05。两种治疗方法治疗前后子宫肌瘤体积的差异无统计学意义。与对照组相比，戈舍瑞林组ER表达的H评分显著降低（54.4对113.2，p = 0.001），而戈舍瑞林组和雷洛昔芬组PR表达的H评分均显著低于对照组（戈舍瑞林组64.8对对照组94.6，雷洛昔芬组73.6对对照组94.6，p = 0.001）。与对照组相比，戈舍瑞林组和雷洛昔芬组bcl-2表达均较高（戈舍瑞林组173.7对对照组94.7，雷洛昔芬组179.7对对照组94.7，p = 0.001）。仅戈舍瑞林组p53表达低于对照组（169.4对205.6，p = 0.001），而雷洛昔芬组与对照组之间无显著变化（201.9对205.6）（p>0.05）。
雷洛昔芬在缩小子宫肌瘤体积方面与戈舍瑞林同样有效。PR表达降低可能是雷洛昔芬治疗中肿瘤生长减少的机制。在两种治疗方式中，子宫肌瘤缩小的机制并非由bcl-2和p53表达介导的凋亡增加，应通过进一步研究进行探讨。
