MacFarlane J K, Fleiszer D, Fazekas A G
Cancer. 1980 Jun 15;45(12):2998-3003. doi: 10.1002/1097-0142(19800615)45:12<2998::aid-cncr2820451220>3.0.co;2-i.
Estradiol receptors were studied both qualitatively and quantitatively in 650 cases of breast cancer to obtain information on molecular forms and relationship with response to endocrine therapy. Cytosol estradiol receptor (ERC) was assayed by a charcoal method following incubations with 3H-estradiol and also by chromatography on Sephacryl columns. Results were classified as positive (10 fmoles/mg P and up), borderline (3-10 fmoles) and negative (0-3 fmoles). It was found that 44.6% of tumors were positive, 14.15% were borderline, and 41.2% were negative. Qualitatively, two major molecular forms of ERC were identified with molecular weights 31,000 and approximately 250,000. ERC level and response to endocrine therapy were correlated in a group of 52 patients. Response rate to hormonal therapy only was 59% in the ERC-positive, 28% in the borderline, and 9% in the ERC-negative group. Combination therapy, including endocrine manipulation, chemotherapy, and/or radiation improved response rates to 66% in the ERC-positive, 40% in the borderline, and 33% in the ERC-negative group. Defects in the translocation of the cytosol estradiol receptor (ERC)-estradiol complex to the nucleus could partly explain the failure of endocrine therapy in 40% of patients with significant ERC. To examine this possibility, 98 cases of breast cancer were examined for both ERC and nuclear translocation of estradiol (ERN). Nuclei were isolated from the low speed sediment and incubated with the ERC-3H-estradiol complex in the presence and absence of an estrogen competitor. After incubation, ERN was extracted from the nuclei and expressed as specifically bound estradiol, fmoles/mg DNA. Of 44 cases with significant ERC, nine had no ERN (20%). In the borderline group of 23 cases, eight had no ERN (34%), and of the 31 cases with zero or negligible ERC 27 had no ERN (87%). Results indicate that ERC-negative cases should be excluded from hormonal therapy and appear to benefit most from chemo- and/or radiation therapy. The absence of ERN in a significant proportion of ERC-positive cases probably contributes to the failure of hormonal manipulation in such patients. The results indicate that the determination of both ERC and ERN could improve the selection of patients for endocrine therapy.
对650例乳腺癌患者的雌二醇受体进行了定性和定量研究，以获取有关分子形式以及与内分泌治疗反应关系的信息。用3H-雌二醇孵育后，通过活性炭法以及在Sephacryl柱上进行色谱分析来测定胞质雌二醇受体（ERC）。结果分为阳性（10飞摩尔/毫克蛋白及以上）、临界（3 - 10飞摩尔）和阴性（0 - 3飞摩尔）。发现44.6%的肿瘤为阳性，14.15%为临界，41.2%为阴性。定性方面，鉴定出ERC的两种主要分子形式，分子量分别为31,000和约250,000。在一组52例患者中，ERC水平与内分泌治疗反应相关。仅接受激素治疗时，ERC阳性组的反应率为59%，临界组为28%，ERC阴性组为9%。包括内分泌干预、化疗和/或放疗的联合治疗使反应率提高到ERC阳性组为66%，临界组为40%，ERC阴性组为33%。胞质雌二醇受体（ERC）-雌二醇复合物向细胞核转位的缺陷可能部分解释了40% ERC显著的患者内分泌治疗失败的原因。为了检验这种可能性，对98例乳腺癌患者的ERC和雌二醇核转位（ERN）进行了检测。从低速沉淀物中分离细胞核，并在有和没有雌激素竞争剂的情况下与ERC - 3H -雌二醇复合物孵育。孵育后，从细胞核中提取ERN，并表示为特异性结合的雌二醇，飞摩尔/毫克DNA。在44例ERC显著的病例中，9例没有ERN（20%）。在23例临界组病例中，8例没有ERN（34%），在31例ERC为零或可忽略不计的病例中，27例没有ERN（87%）。结果表明，ERC阴性病例应排除在激素治疗之外，并且似乎从化疗和/或放疗中获益最大。相当一部分ERC阳性病例中没有ERN可能导致这些患者激素治疗失败。结果表明，同时测定ERC和ERN可以改善内分泌治疗患者的选择。
