Iwase Hirotaka, Zhang Zhenhan, Omoto Yoko, Sugiura Hiroshi, Yamashita Hiroko, Toyama Tatsuya, Iwata Hiroji, Kobayashi Shunzo
Department of Oncology and Endocrinology, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-ku, 467-8601, Nagoya, Japan.
Cancer Chemother Pharmacol. 2003 Jul;52 Suppl 1:S34-8. doi: 10.1007/s00280-003-0592-1. Epub 2003 Jun 19.
The assessment of the estrogen receptor (ER) alpha and the progesterone receptor (PgR) in breast cancer tissues is important for discriminating between hormone-dependent and hormone-independent tumors. ERbeta, a more recently discovered ER, may influence estrogen action through the ERalpha pathway. To evaluate the clinical significance of these receptors in the response to endocrine therapy, we investigated their expression in primary breast cancer tissues. ERalpha and PgR were evaluated using immunohistochemistry (IHC) and enzyme immunoassay (EIA) and ERbeta expression was determined using IHC and reverse transcription-polymerase chain reaction. When the cut-off level of EIA was set at 13 fmol/mg protein for ERalpha and that for IHC was set as an IHC score between 2 and 3, a significant correlation between ERalpha EIA and IHC was seen (concordance rate 88.4%). This indicates that this cut-off level of ERalpha IHC can be adopted to quantify breast cancer prognoses. Furthermore, the tumors with positive expression of ERalpha IHC or PgR IHC using this criterion were significantly related to the response to endocrine therapy. Additionally, tumors with positive expression of ERbeta wild-type tended to have a better response to endocrine therapy than negative ones, and tamoxifen responders tended to exhibit a lower ratio of ERbetacx (one of the ERbeta variants) to ERbeta wild-type than nonresponders. The results concerning ERbeta are not yet fully understood; further investigations and evaluations should analyze the role of ERbeta wild-type and variant type in breast cancer treatment.
评估乳腺癌组织中的雌激素受体（ER）α和孕激素受体（PgR）对于区分激素依赖性肿瘤和激素非依赖性肿瘤至关重要。ERβ是一种较新发现的ER，可能通过ERα途径影响雌激素作用。为了评估这些受体在对内分泌治疗反应中的临床意义，我们研究了它们在原发性乳腺癌组织中的表达。使用免疫组织化学（IHC）和酶免疫测定（EIA）评估ERα和PgR，并使用IHC和逆转录聚合酶链反应测定ERβ表达。当将ERα的EIA临界值设定为13 fmol/mg蛋白质，将IHC的临界值设定为IHC评分为2至3时，观察到ERα EIA与IHC之间存在显著相关性（一致率88.4%）。这表明可以采用这种ERα IHC临界值来量化乳腺癌预后。此外，使用该标准ERα IHC或PgR IHC阳性表达的肿瘤与内分泌治疗反应显著相关。另外，ERβ野生型阳性表达的肿瘤对内分泌治疗的反应往往比阴性肿瘤更好，他莫昔芬反应者的ERβcx（ERβ变体之一）与ERβ野生型的比例往往低于无反应者。关于ERβ的结果尚未完全了解；进一步的研究和评估应分析ERβ野生型和变体类型在乳腺癌治疗中的作用。
