胃癌109雌激素受体与孕激素受体的检测研究

自１９８６－１９９３年采用李氏荧光雌激素组织化学对胃癌１０９例作了雌激素受体、孕激素受体测定，同时对８例非肿瘤病人的胃正常粘膜作了ＥＲ、ＰｇＲ测定。     

雌激素和孕激素受体在胃癌中表达的意义

目的：应用相应单克隆抗体探讨胃癌中雌激素受体（ＥＲ）和孕激素受体ＰＲ表达的临床意义。方法：用ＥＲ、ＰＲ单克隆抗体对１２０例胃癌标本进行免疫组化（ＡＢＣ法）。结果：（１）ＥＲ、ＰＲ在１２例胃癌中阳性表达率分别为３２．５％、３０．８％；两者共同阳性３４例（２８．０％）；（２）ＥＰ、ＰＲ在胃癌Ｂｏｒｒｍａｎ第４型；胃低分化腺癌；粘液腺癌和有淋巴结转移组其阳性率明显高于其它各组（Ｐ〈０．０１）。而与患者年     

卵巢恶性肿瘤雌,孕激素受体状态及其与临床,病理关系的初步探讨

用ＤＣＣ方法检测了５５例卵巢恶性肿瘤及１２例良性肿瘤胞浆雌激素受体（ＥＲ），其中３４例还同时测定了孕激素受体（ＰｇＲ）。结果表明，卵巢恶性肿瘤中４１．８％ＥＲ阳性，４１．２％ＰｇＲ阳性，明显高于良性肿瘤，后者ＥＲ为８．３％，ＰｇＲ为２０．０％。卵巢恶性肿瘤中的ＥＲ、ＰｇＲ与某些临床、病理因素有一定关系。性索间质肿瘤的ＥＲ含量最高（１２６．６ｆｍｏｌｅ／ｍｇ），生殖细胞瘤最低（５．３ｆｍｏｌｅ／ｍｇ）。ＰｇＲ则在性索间质肿瘤及上皮性病中较高（分别为４９．８ｆｍｏｌｅ／ｍｇ及４８．６ｆｍｏｌｅ／ｍｇ）。ＥＲ有随肿瘤组织学分级增高而下降的趋势，ＰｇＲ则无明显规律。两种受体在临床早期组均高于晚期组。经过长期随访发现，ＥＲ、ＰｇＲ阳性患者的５年存活率及平均生存时间均比阴性患者高。本研究初步表明，卵巢恶性肿瘤中亦有部分为性激素依赖性肿瘤，且受体的状态与肿瘤的分化程度及患者的预后有一定关系，这就为卵巢癌的内分泌治疗及对预后的估价奠定了一定的理论基础。     

亲和组化法检测乳腺癌雌,孕激素受体状态的研究

用亲和组化法（半定量分析法）同时检测６７例乳腺癌和良性病变组织印片和石腊切片的ＥＲ／ＰｇＲ状态，二种玻片的ＥＲ阳性、阴性和总符合率分别为８９．５％、９６．６％和９２．５％；双顶阳性（ＥＲ＋／ＰｇＲ＋）、双项阴性（ＥＲ－／ＰｇＲ－）和双项总符合率分别为７５．９％、９２．６％和８２．１％；同种方法检测１５７例随机乳腺癌石腊切片，发现ＥＲ阳性率为５８．６％（９２例）；ＰｇＲ阳性率４８．４％（７６例）．１５７例随访资料提示，受体双项阳性者，其健康良好。乳腺癌分期同ＥＲ／ＰｇＲ状态的比较，ＥＲ＋／ＰｓＲ＋者的Ⅰ、Ⅱ和Ⅲ期病例分别为３７．５％、４５．３％和１７．２％，无Ⅳ期病例：而ＥＲ－／ＰｇＲ－者则为１３．８％、２２．４％和４３．１％．提示，用亲和组化法测定乳腺癌石腊切片ＥＲ／ＰｇＲ状态有较好的可信性。但对乳腺粘液腺癌和派杰氏病宜用切片或针吸涂片。     

胃癌上皮生长因子及其受体与雌激素受体的表达及相互关系

用免疫组化ＡＢＣ方法，检测胃癌和正常胃粘膜中上皮生长因子（ＥＧＦ）及其受体（ＥＧＦＲ）、雌激素受体（ＥＲ）的表达。结果：６４例胃癌中，ＥＧＦ阳性３９例（６０．９％），ＥＧＦＲ阳性３３例（５１．６％），ＥＲ阳性１２例（１８．８％）；５８例正常胃组织中，ＥＧＦ、ＥＧＦＲ阳性各３例，ＥＲ阴性。癌与正常对照组间差异有显著性（Ｐ＜０．０５）。提示，ＥＧＦ、ＥＧＦＲ、ＥＲ与胃癌有关。胃癌ＥＧＦ、ＥＧＦＲ的阳性率又非常显著高于ＥＲ（Ｐ＜０．００５），说明ＥＧＦ、ＥＧＦＲ在胃癌发展中的调节作用远较雌激素重要。结果还提示，ＥＧＦ、ＥＧＦＲ、ＥＲ的相互关系影响胃癌细胞的发生、种植和转移。     

女性激素受体与甲状腺癌,腺瘤及结节性甲状腺肿生长的相关性研究

采用免疫组织化学方法对１９９５￣１９９７年完成的３６０例甲状腺癌、腺癌及结节性甲状腺肿的切除标本进行雌激素受体（ＥＲ）和孕激素受体（ＰｇＲ）检测，探讨女性激素在甲状腺癌的发生过程中所起的作用。结果显示甲状腺癌、腺瘤及结节性甲状腺肿的病变组织中，多可查见例数不等和含量不同的女性激素受体，其中甲状腺癌的ＥＲ、ＰｇＲ阳性表达（５９．０％、６．７％）明显高于结节性甲状腺肿和腺瘤（３４．０％、２５．９％，Ｐ     

200例消化道肿瘤雌激素受体测定

本组１３２例胃癌中有４７例雌激素受体（ＥＲ）阳性（３５．７％）;６８例大肠癌中有３５例ＥＲ阳性（５２％）。ＥＲ阳性率与患者年龄及性别无关,ＢＯｒｒｍａｎｎ’ｓⅣ型与低分化及伴有肝转移胃癌ＥＲ阳性率明显增高（Ｐ＜０．０５）。６８例大肠癌中直肠及左半结肠癌ＥＲ阳性率高于右半结肠癌,高分化腺癌ＥＲ阳性率高于中、低分化,两者均无统计学意义（Ｐ＞０．０５）。研究表明了消化道肿瘤中存在ＥＲ,为今后内分泌治疗提供依据。     

胃癌组织雌激素受体定位及其生物学意义

采用免疫组化ＡＢＣ法对８９例胃癌、１０例癌旁和１１例胃溃疡旁粘膜组织进行雌激素受体（ＥＲ）检测。结果发现：１．癌旁和溃疡旁粘膜上皮均为ＥＲ阴性，胃癌组织ＥＲ阳性率达３３．７％，其ＥＲ颗粒在细胞内分布呈核型、浆型和核浆型；２．胃癌ＢｏｒｒｍａｎｎＩＶ型、低分化癌和伴淋巴结转移的胃癌，其ＥＲ阳性率明显高于其它类型（Ｐ＜０．０５，或Ｐ＜０．０１）。研究表明，ＥＲ阳性表达的胃癌与其恶性生物学行为有正相关性。     

胃癌组织雌激素受体定位及其生物学意义

采用免疫组化ＡＢＣ法对８９例胃癌、１０例癌旁和１１例胃溃疡旁粘膜组织进行雌激素素受体（ＥＲ）检测。结果发现：１．癌裤和溃疡粘膜上皮均为ＥＲ阴性，胃癌组织ＥＲ阳性率达３３．７％，其ＥＲ颗粒在细胞内分布呈核型。浆型和核浆型；２．胃癌ＢｏｒｒｍａｎｎＩＶ型、低分化癌和伴淋巴结转移的胃癌，其ＥＲ阳性率明显高于其它类型（Ｐ〈０．０５，或Ｐ〈０．０１）。研究表明，ＥＲ阳性表达的胃癌与其恶笥生物学行为有正相关性     

甲状腺癌,腺瘤及正常甲状腺组织女性激素受体检测的临床…

采用酶联亲和组化法于石蜡切片对６７例甲状腺癌，２０例腺瘤及３３例瘤旁正常甲状腺组织进行了雌激素受体（ＥＲ）和孕激素受体（ＰｇＲ）检测。结果显示：在腺癌中ＥＲ、ＰｇＲ阳性表达明显高于腺瘤及正常组织（Ｐ〈０．０１），癌组织中乳头状癌阳性率最高，滤泡状癌次之，未分化及其它癌最低，４０岁以前癌组织中ＰｇＲ阳性率高于４０岁以后（Ｐ〈０．０５），女性癌组织中ＰｇＲ阳性率高于男性（Ｐ〈０．０５）。提示，ＥＲ，Ｐ     

大肠癌组织雌激素与孕酮受体检测的初步探讨

本文应用亲和酶标法检测了87例大肠癌组织及80例乳腺癌组织的雌激素受体(ER)和孕酮受体(PR),结果大肠癌的ER、PR阳性率分别为62.1％和46.0％;乳腺癌的ER、PR阳性率分别为65％和56.3％.大肠癌ER、PR阳性率与病人性别、肿瘤部位无关,而绝经后的大肠癌患者,年龄越大,肿瘤分化程度越高,受体阳性率亦越高,与乳腺癌相类似.提示大肠癌与乳癌一样为雌激素依赖性肿瘤,可试行内分泌治疗.     

大肠癌雌激素与孕激素受体检测的探讨

 本文应用E₂-HRP、P_g-HRP亲合组化法对80例大肠癌切除标本进行了ER、P_gR检测，结果大肠癌的ER、P_gR阳性率分别为45.0%和36.3%，大肠癌ER、P_gR阳性率与病人性别，肿瘤部位、大体类型，淋巴结转移无关。而绝经后的大肠癌患者，年龄越大，肿瘤分化程度越高，阳性率亦越高，提示ER、P_gR水平高低可作为选择内分泌治疗和预测病人预后的参考指标。     

Sex hormone receptors in gastric cancer

Gastric adenocarcinoma that originates from mucosal tissue invades submucosa, muscle, and serosa in different stages. The level of progesterone receptors (PgR), estrogen receptors (ER), and androgen receptors (AdR) in the superficial part of gastric cancer tissues (CAs) from 16 patients was determined and compared with that of the corresponding normal gastric mucosal tissues (NLm). There were PgR in all CAs (100%) with values that ranged from 20.5 to 548.4 fmol/mg protein. Eight CAs (50%) had ER values that ranged from 6.8 to 325.1 fmol/mg protein. AdR was found in two CAs with values of 14.7 and 16.4 fmol/mg protein. In NLm, 15 (93.8%) had PgR values that ranged from 7.3 to 473.2 fmol/mg protein and ten (62.5%) had ER values that ranged from 0.9 to 87.9 fmol/mg protein. AdR were present in two NLm with values of 1.5 and 73.5 fmol/mg protein. There was no statistical difference in levels of PgR and ER between CAs and NLm. There were PgR in all gastric cancers and in 93.8% of NLm. The results suggest that gastric mucosa may be the target tissues for progesterone action. Furthermore, the lack of correlation between the levels of ER and PgR in gastric cancer tissue suggests that the PgR in gastric cancers are probably estrogen independent.     

Analysis of Cytosol CA15-3, Carcinoembryonic Antigen, Estrogen and Progesterone Receptors in Breast Cancer Tissues

Cytosol levels of carcinoembryonic antigen (CEA), CA15-3, estrogen receptor (ER) and progesterone receptor (PgR) of 194- primary breast cancer tissues were measured. ER and PgR determined by enzyme immunoassay methods correlated inversely with Page's grades of histological atypia and mitotic rate. Cytosol CA15-3 correlated inversely with the grades of tubular and nuclear atypia and positively with the mitotic rate. CA15-3 correlated positively with ER and PgR. Cytosol CEA showed no correlation with the pathological grade or hormone receptor status. These results indicate that hormone receptor-positive breast cancers tend to have more differentiated morphology and slower growth rate than those without those receptors and that the cytosol CA15-3 level may reflect some of the intrinsic malignant potency, particularly the growth rate, of breast cancer. Cytosol CA15-3 as well as the hormone receptor status may have prognostic value for patients with breast cancer.     

胃癌的雌孕激素受体状况与预后关系的临床探讨

目的探讨胃癌的雌、孕激素受体状况与预后关系。方法对３４例胃癌根治术后的标本以免疫组化（ＡＢＣ法）作ＥＲ、ＰＲ测定,并作５ａ随访。结果ＥＲ、ＰＲ阳性率皆为４１．２％（１４／３４）。高分化胃癌ＥＲ、ＰＲ阳性率（２６．９％）明显低于分化差的胃癌组（８７．５％）。随访５ａ,存活者中原来标记的ＥＲ、ＰＲ阳性率较低,仅为２０％。结论胃癌根治术后除辅以化疗外,ＥＲ、ＰＲ阳性者加内分泌治疗可能会提高５ａ生存率。     

Rates for breast cancer characteristics by estrogen and progesterone receptor status in the major racial/ethnic groups

It has been reported that age-specific breast cancer rates vary by estrogen receptor and progesterone receptor status. We report breast cancer rates for age-at-diagnosis, stage-at-diagnosis, histological grade and type by estrogen (ER) and progesterone (PgR) receptor status in six major racial/ethnic groups. The average annual age-adjusted rates for breast cancers with estrogen receptor positive (ER⁺), ER^–, progesterone receptor positive (PgR⁺), PgR^–, ER⁺PgR⁺, ER⁺PgR^–, ER^–PgR⁺ and ER^–PgR^– are determined from 123,732 breast cancers with known ER status, diagnosed from 1992 to 1998 from 11 Surveillance, Epidemiology, and End Results (SEER) cancer registries. For each racial/ethnic group, their ER⁺ (ER⁺PgR⁺ and ER⁺PgR^–) age-specific rates increased with age (but at a slower pace after ages 50–54) while their ER^– (ER^– PgR⁺ and ER^–PgR^–) age-specific rates did not increase after ages 50–54. The rank orders of the rates among the racial/ethnic groups varied by ER/PgR status. The stage I rates were greater than the stage II rates for the ER/PgR groups except for ER^– and ER^–PgR^– cancers. The grade 2 (moderately differentiated) rates were greater than the grades 3 and 4 (poorly differentiated and undifferentiated cancers) rates for ER⁺ cancers, but not for ER^– cancers. These results suggest that although breast cancer is a disease with enormous heterogeneity, the multiple types of breast cancer can be separated into distinct subgroups by their ER status, and perhaps by their ER/PgR status, and their cancer characteristics may be important in understanding the multiple nature of breast cancer.     

Sex hormone receptors in human thyroid tissues

The behavior of sex hormone receptors was studied in the cytosol of thyroid tissue samples in order to clarify the effects of sex hormones on diseases of the thyroid. Androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PgR) were assayed using the dextran-coated charcoal (DCC) method and analyzed by the method of Scatchard. Androgen receptor, ER, and PgR were negative in all of the cytosol prepared from normal thyroid tissues. However, the positive rates for the receptors in the neoplastic and nonneoplastic tissues were 22% for AR, 29% for ER, and 18% for PgR. Especially, the incidence of ER was significantly higher in neoplastic lesions than normal tissues. These data suggest that sex hormones, especially estrogen, may play a role in diseases of the thyroid.     

Significance of immunohistochemical assessment of steroid hormone receptor status for breast cancer patients

The assessment of steroid hormone receptors in resected breast cancer tissues is essential to decide whether endocrine therapy is indicated and to select the best treatment for each patient on the basis of receptor status. Both enzyme immunoassay (EIA) and immunohistochemistry (IHC) have been generally used as methods for examination of estrogen receptor (ER) and progesterone receptor (PgR). In some patients, receptor status cannot be examined for various reasons. A questionnaire survey in Japan clarified that ER status is not examined in approximately 40% of patients receiving breast conserving surgery. To eliminate "receptor unknown" cases, IHC examination on paraffin-embedded tissue is useful to assess the in situ receptor status. The concordance rate of ER and PgR status between EIA and IHC is very high and a study of 88 cases revealed a 97.7% concordance for ER and 92.0% for PgR at a cutoff point of 10%. The cutoff point of IHC is controversial and some studies demonstrated that patients showing 1% ER positive cancer cells would benefit from endocrine therapy. On the other hand, immunohistochemical expression of receptors is heterogeneous and some patients with ER negative invasive tumors have ER positive intraductal components. A study of 65 breast cancers demonstrated that ER positive intraductal components were detected in 3.1% cases of ER negative invasive lesions. According to these results and the recommendation of the St. Gallen International Conference, IHC is thought to be more useful than EIA in the assessment of steroid hormone receptor status for breast cancer patients.     

Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels

A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p=0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p=0.53 and p=0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment.In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.