Effect of tamoxifen on Ki67 labelling index in human breast tumours and its relationship to oestrogen and progesterone receptor status.

Effect of tamoxifen on Ki67 labelling index in human breast tumours and its relationship to oestrogen and progesterone receptor status.
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DOI:
10.1038/bjc.1993.111
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发表时间:
1993-03
影响因子:
8.8
通讯作者:
Anderson E
Anderson E
中科院分区:
医学1区
文献类型:
--
作者:
Clarke RB;Laidlaw IJ;Jones LJ;Howell A;Anderson E

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本研究旨在研究他莫昔芬对乳腺肿瘤雌激素和孕激素受体(ER和PR)水平以及Ki 67抗体所定义的增殖的影响。一组原发性乳腺癌患者随机接受他莫昔芬(n = 59)或安慰剂(n = 44)治疗的诊所和手术之间的时间间隔(中位数21天)。对治疗前后获得的乳腺肿瘤活检组织的冷冻切片进行免疫细胞化学染色,以获得含有ER和PR的细胞核的百分比以及Ki 67标记指数(LI)。他莫昔芬治疗组患者第一次活检的Ki 67 LI中位数为5.6%,第二次活检时降至3.0%(Wilcoxon配对检验P < 0.001),而安慰剂治疗组患者第一次活检的Ki 67 LI中位数为5.4%,第二次活检的Ki 67 LI中位数为5.75%(无显著差异)。比较治疗前后的中位%ER或%PR染色时,未观察到显著差异。Ki 67 LI倾向于随着组织学分级的增加而增加,并且与ER + ve(> 5%核染色)的肿瘤相比,ER - ve的肿瘤中Ki 67 LI更大,中值分别为7.8%和4.3%(通过Mann-Whitney U检验,P = 0.011)。然而,抗雌激素治疗后肿瘤Ki 67 LI的下降与ER和PR状态无关,也不能预测短期随访后的复发。据我们所知,这是第一次他莫昔芬治疗已被证明可以减少体内人乳腺肿瘤中的Ki 67 LI。这些数据表明,用Ki 67抗体染色可用于监测对抗雌激素治疗的反应。
This study aimed to investigate the effect of tamoxifen on breast tumour levels of oestrogen and progesterone receptor (ER and PR) and proliferation as defined by the Ki67 antibody. A group of primary breast cancer patients was randomised to receive either tamoxifen (n = 59) or placebo (n = 44) treatment in the interval between clinic and surgery (median 21 days). Frozen sections of breast tumour biopsies obtained before and after treatment were stained immunocytochemically to obtain the percentage of nuclei containing ER and PR, and a Ki67 labelling index (LI). Tamoxifen-treated patients had a median Ki67 LI of 5.6% in the first biopsy falling to 3.0% in the second biopsy (P < 0.001 by Wilcoxon's matched pairs test), whereas placebo-treated patients had a median Ki67 LI of 5.4% in the first biopsy and 5.75% in the second (no significant difference). No significant differences were observed when the median %ER or %PR staining before and after treatment were compared. The Ki67 LI tended to increase with increasing histological grade and was greater in tumours that were ER - ve compared to those that were ER + ve (> 5% nuclei stained), median 7.8% and 4.3% respectively (P = 0.011 by Mann-Whitney U-test). However, the decline in tumour Ki67 LI following anti-oestrogen treatment failed to correlate with ER and PR status or to predict recurrence over a short follow-up period. To our knowledge, this is the first time that tamoxifen treatment has been shown to reduce the Ki67 LI in human breast tumours in vivo. These data indicate that staining with the Ki67 antibody may be useful in monitoring response to anti-oestrogen therapy.