绝经期乳腺癌妇女服用他莫昔芬后子宫内膜雌、孕激素受体变化及Ki-67的表达

目的评估他莫昔芬(TAM)对绝经后妇女子宫内膜的雌激素样作用与性激素受体的改变是否相关,以及细胞增生核抗原Ki-67在子宫内膜中的表达。方法选择46例绝经后因乳腺癌服用TAM超过6个月妇女的子宫内膜为研究组,同时选择18例绝经后妇女的萎缩型子宫内膜作为对照组。采用免疫组织化学法测定雌激素受体(ER)、孕激素受体(PR)及Ki-67在子宫内膜中的表达。结果与对照组比较,PR及Ki-67在TAM组内膜腺上皮细胞呈明显高表达(0.46±0.05比0.35±0.06,P=0.028;15.41±4.83比9.05±5.52,P=0.009);ER在TAM组内膜腺上皮细胞虽然呈高表达,但差异无统计学意义(0.47±0.06比0.43±0.06,P=0.063)。结论绝经后乳腺癌妇女服用TAM后能够引起子宫内膜增生,TAM雌激素样作用与病理诊断和服用时间无关,这可能是子宫内膜息肉及内膜癌的发病机制之一。

Effects of Tamoxifen on Expression of Oestrogen Receptors, Progesterone Receptors and Ki-67 in Postmenopausal Endometrium

Objective To investigate the effects of tamoxifen(TAM) on expression of oestrogen receptors(ER),progesterone receptors(PR)and Ki-67 antigen in postmenopausal endometrium.Methods Forty-six postmenopausal breast cancer patients receiving 20 mg/d TAM for at least six months were examined by hysteroscopy and endometrial biopsy,and eighteen age-matched,non-hormonally treated patients with atrophic endometrium post vaginal hysterectomy because of uterine prolapse served as control groups.Immunohistochemical studies for the expression of ER,PR and Ki-67 antigen in endometrium were performed.Results There were significantly increased levels of expression of PR((0.46±)0.05 vs 0.35±0.06,P=0.028) in glandular epithelium in tamoxifen-associated endometrium compared with atrophic endometrium.Also,Ki-67 antigen was expressed more frequently in glandular epithelium in the tamoxifen samples(15.41±4.83 vs 9.05±5.52,P=0.009).The expression of ER in glandular epithelium was higher but did not differ statistically between tamoxifen-associated endometrium and atrophic endometrium(0.47±0.06 vs 0.43±0.06,P=0.063).Conclusion In postmenopausal women tamoxifen exerts a proliferative effect on the endometrium,as measured by Ki-67 antigen.The tamoxifen-associated changes in endometrial PR support an estrogenic effect that is independent of histological diagnosis and duration.This may contribute to the pathogenesis of tamoxifen-associated polyps and carcinomas.