Preoperative treatment of uterine leiomyomas: clinical findings and expression of transforming growth factor-beta3 and connective tissue growth factor.

Marianna De Falco, Stefania Staibano, Francesco Paolo D'Armiento, Massimo Mascolo, Gaetano Salvatore, Anna Busiello, Ilma Floriana Carbone, Fabrizio Pollio, Andrea Di Lieto
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引用次数: 31

Abstract

Objective: To evaluate the clinical features and the expression of transforming growth factor-beta3 (TGF-beta3) and connective tissue growth factor (CTGF) in myometrium and uterine leiomyomas after preoperative treatment with gonadotropin-releasing hormone-analogs (GnRH-a) and tibolone.

Methods: Twenty-three patients received 3.75 mg leuprolide acetate depot for 4 months. Twenty-two patients received the same therapy plus 2.5 mg tibolone daily. Patients underwent uterine surgery after therapy. Twenty-two untreated patients underwent surgery directly. Hematologic tests, bone mineral density (BMD) measurement, and ultrasonographic evaluation of uterine volume were performed before and after treatment. Menorrhagia and pelvic pain were evaluated with a visual analog scale. Hot flushes were recorded in daily diaries. Immunohistochemical expression of TGF-beta3 and CTGF in myometrium and myoma samples was evaluated semiquantitatively.

Results: After therapy, hemoglobin and iron levels similarly increased in both groups. BMD significantly decreased only in the GnRH-a group. Uterine volume similarly decreased in both groups. No patient had menorrhagia or pelvic pain at the end of therapy. The number of hot flushes increased after the first month in the GnRH-a group; in the GnRH-a plus tibolone group, it remained constant and was lower. In untreated cases, TGF-beta3 and CTGF smooth muscle cell immunoexpression was lower in myometrium than in leiomyomas. After medical treatment, growth factor immunoexpression remained unchanged in myometrial samples and was reduced in leiomyomas. Endothelial cells showed strong immunopositivity, both in untreated and in treated cases.

Conclusion: This study focuses on the effects of GnRH-a and tibolone on TGF-beta3 and CTGF expression in myometrium and myomas and supports the hypothesis of a pathogenetic role of these growth factors in uterine fibromatosis.

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子宫平滑肌瘤的术前治疗:转化生长因子- β 3和结缔组织生长因子的临床表现及表达。
目的:探讨促性腺激素释放激素类似物(GnRH-a)和蒂勃龙术前治疗后子宫肌瘤和子宫平滑肌瘤的临床特征及转化生长因子- β 3 (tgf - β 3)和结缔组织生长因子(CTGF)的表达。方法:23例患者接受3.75 mg醋酸leuprolide depot治疗,疗程4个月。22名患者接受了相同的治疗,每天加2.5毫克的替博龙。治疗后患者行子宫手术。22例未经治疗的患者直接接受手术治疗。治疗前后分别进行血液学检查、骨密度(BMD)测量和子宫体积超声评估。月经过多和盆腔疼痛用视觉模拟量表评估。潮热被记录在每日日记中。半定量评价肌层和肌瘤标本中tgf - β 3和CTGF的免疫组化表达。结果:治疗后,两组患者血红蛋白和铁水平均明显升高。只有GnRH-a组骨密度显著降低。两组的子宫体积均明显减小。在治疗结束时,没有患者出现月经过多或盆腔疼痛。GnRH-a组在第一个月后潮热次数增加;在GnRH-a加替博龙组中,它保持不变并且更低。在未经治疗的病例中,tgf - β 3和CTGF平滑肌细胞免疫表达在肌层中低于平滑肌瘤。药物治疗后,生长因子免疫表达在子宫肌瘤样本中保持不变,而在平滑肌瘤中则降低。内皮细胞在未治疗和治疗的病例中均表现出很强的免疫阳性。结论:本研究关注了GnRH-a和替勃龙对子宫肌瘤和子宫肌瘤中tgf - β 3和CTGF表达的影响,支持了这些生长因子在子宫纤维瘤病发病中的作用。
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