乳腺癌组织中ER、PR和CEA相关性研究

应用免疫组化技术亲和组化法和ＡＢＣ法,检测了１０６例乳腺癌组织中ＥＲ、ＰＲ和ＣＥＡ水平。其阳性率依次为８３％、８１．１％和８８．７％。其中７９．２％的乳腺癌ＥＲ和ＰＲ表达一致。在９８例ＥＲ和／或ＰＲ阳性乳腺癌中有９２例（９３．９％）呈ＣＥＡ阳性,８例ＥＲ和ＰＲ阴性乳腺癌中６例（７５％）为ＣＥＡ阴性,８９％乳腺癌ＣＥＡ与ＥＲ和ＰＲ表达一致。在癌的分级表达中,随着癌的组织学分级增高ＣＥＡ阳性率增高,而ＥＲ和ＰＲ阳性率减低。结果表明,乳腺癌ＥＲ、ＰＲ和ＣｈＡ表达可反映肿瘤的不同生物学特征。同时检测三者对选择内分泌治疗及判断预后更有意义。     

乳腺癌ConA、LCA、PSA免疫组化研究

运用ＡＢＣ法研究５０例乳腺癌三种凝集素受体（Ｌｅｃｔｉｎ－Ｒ）的表达,并以乳腺纤维瘤和乳腺小叶增生症各１０例作为对照。结果表明：该三种凝集素受体在乳腺良、恶性病变中的表达率无显著性差异。ＣＯｎＡ－Ｒ在乳腺癌以胞浆型定位为主,在纤维腺瘤则以胞膜型多见（Ｐ＜０．０５）。ＬＣＡ－Ｒ和ＰＳＡ－Ｒ在乳腺三种病变中均以胞浆型为主。ＣｏｎＡ－Ｒ与乳腺癌分化程度具良好的相关性;ＬＣＡ－Ｒ与乳腺癌瘤体大小有关。该三种凝集素受体与ＥＲ、ＰＲ及ＣＥＡ的表达未显示密切的关联。     

血管紧张素Ⅱ对大鼠心肌肌浆网Ca~(2+),Mg~(2+)-ATPase基因转录调节的影响

观察血管紧张素Ⅱ（ＡｎｇⅡ）对心肌肌浆网Ｃａ２＋,Ｍｇ２＋－ＡＴＰａｓｅ基因（ＳＥＲＣＡ２ａ）转录调节的影响,评价ＤＭＰ８１１对此效应的干预作用．６周龄雄性ＳＤ大鼠随机分为３组,每组６只．组１：生理盐水输注;组２：ＡｎｇⅡ输注＋ＤＭＰ８１１管饲（３ｍｇ·ｄ－１·ｋｇ－１）;组３：ＡｎｇⅡ输注（２００ｎｇ·ｍｉｎ－１·ｋｇ－１．１周后称其体重,取心脏并称重,提取心脏总ＲＮＡ后采用Ｎｏｒｔｈｅｒｎｂｌｏｔ的方法检测ＳＥＲ－ＣＡ２ａ的转录水平,采用ＲＴ－ＰＣＲ检测ＡｎｇⅡ１型受体（ＡＴ１）ｍＲＮＡ水平．实验后,组３心重（ＣＷ）、心重／体重（Ｃ／Ｂ）、ＡＴ１受体转录水平均高于组１（分别增加４．７±０．４％,４．９±０．９％和２４．７±３．５％;Ｐ＜０．０１）,而ＳＥＲＣＡ２ａ基因转录水平显著低于组１（降低２０．１±３．０％,Ｐ＜０．０１）,并且ＳＥＲＣＡ２ａｍＲＮＡ水平与ＡＴ１受体ｍＲＮＡ水平呈负相关（ｒ＝－０．７４,Ｐ＜０．０１）．ＡｎｇⅡ导致的上述改变能被ＤＭＰ８１１完全阻断．ＡｎｇⅡ通过其Ⅰ型受体的介导,诱导了ＳＥＲＣＡ２ａ的转录下调     

穴位激光照射对兔子宫类固醇激素受体的影响

对兔用Ｈｅ－Ｎｅ激光照射穴位,照射外生殖器,用类固醇激素受体测定法测定子宫雌二醇受体（ＥＲ）和孕酮受体（ＰＲ）含量。照射穴位后部分实验组的ＥＲ和ＰＲ浓度上升,与正常对照组相比较有显著或极显著差别（Ｐ＜０．０５,Ｐ＜０．０１）,ＥＲ提高１．７－３．２倍,ＰＲ提高２．７－３．７倍。实验结果提示激光可通过类固醇激素受体浓度的提高,在受体水平上影响机体代谢。     

前列腺专一蛋白因子抑制雄激素受体与其应答元件作用

雄激素受体片段（氨基酸：３５９￣７３２）以及糖皮质激素受体片段（氨基酸：３９６￣５４８）以与ＧＳＴ融合形式在大肠杆菌中分别表达为ＧＳＴ－ＡＲ和ＧＳＴ－ＧＲ两种融合蛋白,它们含有ＤＮＡ结合结构域和一些旁侧氨基酸,凝胶阻滞分析表明能与雄激素／糖皮质激素应答元件（ＡＲＥ／ＧＲＥ）在体外结合。本文报道在大鼠前列腺中发现有抑制ＧＳＴ－ＡＲ以及ＧＳＴ－ＧＲ与ＡＲＥ／ＧＲＥ结合的因子,抑制作用与ＡＲＥ／ＧＲＥ来     

Epstein—Barr病毒BCRF1基因重组质粒的构建及其在真核细胞中的表达

应用基因重组技术,把编码ＥＢ病毒早期蛋白的ＢＣＲＦ１基因重组于真核表达载体ｐＳＧ５中,并使该基因在乳地鼠肾（ＢＨＫ）传代细胞中获得良好表达,表达率为０．５％。血清学实验证实,鼻咽癌、类风湿性关节炎病人和正常人血清中均不同程度地含有ＩｇＧ／ＢＣＲＦ１抗体,抗体阳性率分别为９２％、８６％和７７％,几何平均滴度（ＧＭＴ）分别是１：１６．３５、１：１４．７２和１：１０．１５。两组病人和正常人血清中ＩｇＡ／ＢＣＲＦ１抗体阳性率和滴度之间有较大差别,它们的阳性率分别是７４％、７１％和１２％,ＧＭＴ分别是１：１２．３２,１：１０．５６和１：２．３５。还证实,鼻咽癌和类风湿性关节炎病人血清中ＩｇＡ／ＢＣＲＦ１和ＩｇＡ／ＥＡ（早期抗原）抗体阳性率和滴度间有很好的相关性,此为首次报导。重组表达质粒ｐＳＧ５－ＢＣＲＦ１的构建和表达为进一步研究ＢＣＲＦ１基因在病毒感染和肿瘤免疫中的作用创造了条件。本文就质粒的构建和３组血清中ＩｇＡ／ＢＣＲＦ１、ＩｇＡ／ＢＣＲＦ１、ＩｇＡ／ＥＡ和ＩｇＧ／ＢＣＲＦ１抗体间的关系和有关问题进行了讨论。     

细支气管肺泡细胞增生和细支气管肺泡细胞癌内生长因子和蛋白激酶C的表达

表皮生长因子（ＥＧＦ）、转化生长因子－α（ＴＧＦα）、表皮生长因子受体（ＥＧＦＲ）和蛋白激酶Ｃ（ＰＫＣ）与细胞生长、增殖分化调节和细胞癌变有密切关系。作者用免疫组织化学方法检测了细支气管肺泡细胞增生（ＢＡＨ）和细支气管肺泡细胞癌（ＢＡＣ）的ＥＧＦ、ＴＧＦα、ＥＧＦＲ和ＰＫＣ表达。结果表明：ＢＡＣ中的ＥＧＦ、ＴＧＦα阳性率和阳性强度以及ＥＧＦＲ、ＰＫＣ阳性强度均明显高于ＢＡＨ。ＢＡＨ的重度不典型增生病例,其ＥＧＦ、ＴＧＦα、ＥＧＦＲ和ＰＫＣ均呈高表达。ＴＧＦα、ＥＧＦＲ和ＰＫＣ三者在ＢＡＣ和ＢＡＨ中的表达存在明显相关性。提示：ＴＧＦα及其受体ＥＧＦＲ和ＰＫＣ是细支气管肺泡细胞增生、恶性转化和肺泡癌细胞失控生长的重要因素。     

中枢应用β-内啡肽对大鼠血浆唾液酸水平的影响以及与免疫功能的关系

实验选择体重２００－２５０ｇ健康Ｗｉｓｔａｒ大鼠６４只,采用麻醉大鼠中枢微量注射,分光光测定法及免疫组织化学法,研究侧脑室,弓状核（ＡＲＣ）区注射β－内啡肽（β－ＥＰ）对大鼠血浆唾液酸（ＳＡ）水平的影响及与免疫功能的关系,结果表明：（１）侧脑室注射β－ＥＰ可明显降低血浆ＳＡ水平;（２）血浆ＳＡ水平在ＡＲＣ区注射β－ＥＰ后明显降低,此效应可被Ｍ胆碱受体阻断剂阿托品或切断双侧颈迷走神经所阻断;（３）Ａ     

外周炎性刺激条件下大鼠脊髓背角PPE mRNA及L-ENK样品和μ阿片受体样阳性结构的变化

以鹿角菜胶（ＣＡＲ）注射到大鼠一侧后爪的足底皮下作为伤害性刺激模型,分别于ＣＡＲ刺激后６、１２ｈ和１、３ｄ处死动物,对照组动物仅将盐水注入一侧后爪足底皮下,用原位杂交法和免疫组织化学法观察前原脑啡肽（ＰＰＥ）ｍＲＮＡ阳性神经元、亮氨酸脑啡肽（Ｌ－ＥＮＫ）和μ阿片受体（ＭＯＲ）样阳性结构在大鼠脊髓背角（ＳＤＨ）的分布和变化。对照组大鼠ＳＤＨ内可见到大量ＰＰＥｍＲＮＡ阳性神经元,这些阳性神经元主要分布于Ⅰ、Ⅱ层和Ⅴ、Ⅵ层,ＣＡＲ刺激后６ｈ,刺激侧ＳＤＨ中ＰＰＥｍＲＮＡ阳性神经元的数量明显增多,１２ｈ和１ｄ达到最高水平,３ｄ时略有下降,但仍高于正常水平。Ｌ－ＥＮＫ样阳性纤维和终末主要分布于正常大鼠ＳＤＨ的Ⅰ、Ⅱ层,ＣＡＲ刺激后１ｄ,Ｌ－ＥＮＫ样阳性结构在刺激侧ＳＤＨ中的密度略有升高,３ｄ后下降直至低于正常水平。ＭＯＲ阳性胞体和纤维主要分布于ＳＤＨ的Ⅱ层,ＣＡＲ刺激后１ｄ,刺激侧Ⅱ层中ＭＯＲ阳性结构明显增加,并持续到刺激后３ｄ。上述结果提示阿片类物质在伤害性信息调控中具有重要作用。     

孤生受体的相互作用对视黄酸应答元件的影响

孤生受体ＣＯＵＰ－ＴＦ和ｎｕｒ７７的功能及其作用机理仍未阐明．以ＤＮＡ瞬时转染和测定氯霉素乙酰转移酶（ＣＡＴ）活性,以及凝胶阻抑测定,分析ＣＯＵＰ－ＴＦ和ｎｕｒ７７的相互作用对视黄酸应答元件（ＲＡＲＥｓ）的影响．实验表明,ＣＯＵＰ－ＴＦ通过降低ＲＡＲＥｓ的基础活性,来增强ＲＡＲＥ对视黄酸（ＲＡ）的敏感性,而ｎｕｒ７７则拮抗ＣＯＵＰ－ＴＦ的作用．ｎｕｒ７７能够加强不同ＲＡＲＥｓ的转录活性,并且与ＲＡ的诱导无关．结果证实,ｎｕｒ７７通过与ＣＯＵＰ－ＴＦ的直接作用而对ＲＡＲＥｓ产生影响,从而抑制ＣＯＵＰ－ＴＦ与ＲＡＲＥｓ结合和ＣＯＵＰ－ＴＦ的转录活性     

Alkaline phosphatases and steroid receptors in human breast cancer

Estrogen receptors (ER), progesterone receptors (PR) and alkaline phosphatases (AP) were measured in 150 tumors from patients who underwent mastectomy for primary breast cancer. The percentage of ER positive samples was inversely related to the AP activity ranging from 88.9% in low activity samples (less than 30 U/mg prot.) down to 30.6% in the high activity ones (greater than 400 U/mg prot.). When considering only ER positive samples, the ER content was inversely related to the AP activity. This could not be demonstrated for PR. Therefore, the authors suggest the hypothesis that in human breast cancer, the AP may play a role in the dephosphorylation of the ER molecule and in the consequent modulation of its binding capability.     

雌、孕激素受体及C-erbB2在子宫内膜癌中的表达和意义

目的探讨雌、孕激素受体（Estrogen Receptor ER、Progesterone Receptor PR）及C-erbB2在子宫内膜癌中的表达与临床病理参数的关系。方法采用免疫组织化学技术检测56例子宫内膜癌患者子宫内膜中ER、PR及C-erbB2的表达,并对56例患者的临床病理资料进行回顾性分析。结果子宫内膜癌患者内膜ER、PR及C-erbB2阳性率分别为41.07%、57.14%、53.57%。子宫内膜癌中ER表达与肿瘤分化程度、年龄、有无淋巴结转移呈负相关;PR表达与肿瘤组织学类型、分化程度、年龄、浸润肌层深度及有无淋巴结转移均呈负相关;而C-erbB2的表达与内膜癌分化程度、有无淋巴结转移呈正相关。结论激素依赖型子宫内膜癌ER、PR及C-erbB2表达水平均反映了子宫内膜癌的生物学行为,三者的测定对估计预后和指导术后辅助治疗具有重要意义。     

甲状腺乳头状癌CT及MRI影像征象及其与雌激素受体、孕激素受体、C-myc表达的相关性研究

摘要 目的：探讨甲状腺乳头状癌（PTC）计算机断层扫描（CT）、磁共振成像（MRI）影像征象及其与雌激素受体（ER）、孕激素受体（PR）、C-myc表达的相关性。方法：回顾性分析2019年6月-2020年12月于我院74例诊断为PTC患者的计算机断层扫描CT、MRI影像资料,以手术病理结果作为金标准。分析患者的CT、MRI影像学特征。采用免疫组织化学染色分析ER、PR、C-myc的表达情况。采用Spearman秩相关分析评价CT、MRI影像学特征及其与ER、PR、C-myc表达水平的相关性。结果：PTC患者CT、MRI主要表现为混杂密度/信号,多数病灶形态不规则,病灶突破甲状腺被膜外缘呈咬饼征改变、侵犯周围组织及病灶内见细颗粒状钙化时提示恶性程度较高,患者早期出现颈部淋巴结转移较多。ER、PR、C-myc阳性表达者分别为51例（68.92%）、44例（59.46%）、64例（86.49%）。C-myc阳性表达与PTC肿瘤直径有关,组间差异有统计学意义（P＜0.05）;ER、PR、C-myc阳性表达与PTC形态、咬饼征及淋巴结转移有关,组间差异均有统计学意义（P＜0.0）;ER、C-myc阳性表达与PTC边界有关,组间差异有统计学意义（P＜0.05）;ER阳性表达与PTC增强后病灶范围缩小/模糊有关,组间差异有统计学意义（P＜0.05）;ER、PR、C-myc阳性表达与其余CT、MRI影像学表现特征无关,组间差异均无统计学意义（P＞0.05）。咬饼征与PR、C-myc表达水平呈正相关（P＜0.05）,淋巴结转移状态与ER、PR、C-myc表达水平呈正相关（P＜0.05）,其余影像学表现特征与ER、PR、C-myc表达水平无明显相关性（P＞0.05）。结论：CT、MRI影像征象可在一定程度上评估PTC患者肿瘤细胞的生物学行为,可间接反映肿瘤分化程度、浸润程度等情况,对指导临床综合治疗及评估患者预后可提供客观依据。     

ER/PR阳性和阴性乳腺癌的定量蛋白质组学和生物信息学比较研究

目的:建立雌/孕激素受体(ER/PR)阴性和阳性乳腺癌的蛋白质表达谱,寻找ER/PR阴性和阳性乳腺癌中差异表达蛋白,为乳腺癌患者提供新的预后预测指标和治疗新靶点。方法:应用蛋白质组学i TRAQ技术建立ER/PR阳性和阴性乳腺癌的蛋白质差异表达谱,鉴定两组乳腺癌的差异表达蛋白,对部分差异表达蛋白进行生物信息学分析,包括蛋白功能注释和分类GO分析和KEGG通路分析。结果:应用i TRAQ蛋白质组学技术对乳腺癌组织进行了蛋白组学分析,鉴定出ER/PR阳性和阴性组间有差异表达的蛋白4999种,以ER/PR阳性:ER/PR阴性≥3为上调标准,确定ER/PR阳性组上调蛋白101种。以ER/PR阳性:ER/PR阴性≤0.5为下调标准,ER/PR阳性组下调蛋白122种。GO分析结果显示ER/PR受体阴性和阳性乳腺癌的差异表达蛋白的分子功能、生物过程、细胞定位较为复杂,并且在上调蛋白和下调蛋白上存在分布差异。KEGG通路分析发现部分差异表达蛋白涉及201条信号通路。结论:ER/PR阳性和阴性乳腺癌间存在差异表达蛋白,这些蛋白涉及复杂的分子功能、生物过程和信号通路。     

Interstitial Cajal-like cells (ICLC) as steroid hormone sensors in human myometrium: immunocytochemical approach

Expression of estrogen (ER) and progesterone (PR) receptors was investigated in cultured human normal myometrial cells (non-pregnant uterus, fertile period). The ER and PR expression was studied by immunohistochemistry and immunofluorescence on either myocytes or interstitial Cajal-like cells (ICLC). Only those cells double immunostained for c-kit and steroid receptors were considered as ICLC. ER and/or PR immunoreactivity was localized in ICLC, primarily concentrated at the nucleus level, but it was also observed in the cell body (cytoplasm) and processes. Stronger immunopositive reaction in the ICLC nucleus for PR than for ER was noted. Under our experimental conditions, a clear positive repeatable reaction for steroid receptors could not be detected in myocytes. In conclusion, these data suggest that ICLC could be true hormonal 'sensors', possibly participating in the regulation of human myometrial contractions (via gap junctions with myocytes and/or by paracrine signaling).     

Immunochemistry for oestrogen receptor,progesterone receptor and HER2 on cell blocks in primary breast carcinoma

K. Kumar S, N. Gupta, A. Rajwanshi, K. Joshi and G. Singh Immunochemistry for oestrogen receptor, progesterone receptor and HER2 on cell blocks in primary breast carcinoma Objective: Steroid receptors and human epidermal growth receptor 2 (HER2) have been used for predicting response to treatment in breast cancers. Fine needle aspiration cytology can provide highly cellular material and can be used for such analysis. The present study was undertaken to assess the reliability of oestrogen and progesterone receptor (ER, PR) status and HER2 as demonstrated by immunochemistry (IHC) on cell blocks from breast carcinoma cases, in comparison with histological sections. Methods: IHC for ER, PR and HER2 was performed on cell blocks and their corresponding tissue sections of 50 primary pre‐chemotherapy breast carcinomas. Positivity for ER and PR was scored according to the Allred scoring system. Strong membranous positivity in more than 30% of tumour cells was considered positive for HER2. The tumours were classified as luminal A, luminal B, HER2‐over‐expressing and triple negative on the basis of ER, PR and HER2 status and results on cell blocks compared with histological sections. Results: Correlation between immunostaining on cell blocks and the corresponding tumour tissues revealed a concordance rate for ER, PR and HER2 of 90% [Correlation coefficient (r) = 0.79], 94% (r = 0.86) and 90% (r = 0.76), respectively. Including five cases in which cell blocks were either ER or PR positive, 43/50 cases (86.0%) could be correctly classified on cell block immunostaining alone. The main reasons for seven discordant cases included technical errors (sampling error and staining error) and interpretational error in HER2 evaluation on cell blocks; the core biopsy was inadequate in one, and apparently false negative for HER2 in another. Conclusion: Cell blocks are useful in the assessment of hormone receptor status and HER2 by IHC, especially in cases of locally advanced breast cancer for planning neoadjuvant chemotherapy. It is highly recommended to have good quality cell blocks and quality control of their interpretation.     

非小细胞肺癌BRCA2的表达及其与ER、PR及c—erbB-2的相关性研究

目的在非小细胞肺癌中检测乳腺癌易感基因（BRCA2）的表达和ER、PR及c-erbB-2蛋白表达特点,探讨BRCA2的表达与ER、PR及c-erbB-2之间的相关性。方法免疫组织化学SP法检测了42例手术切除的非小细胞肺癌中ER、PR、c-erbB-2和BRCA2蛋白表达,根据各种临床病理因素分组进行BRCA2表达阳性率统计学分析。结果BRCA2蛋白表达阳性15例（35．7％）;BRCA2蛋白表达阳性率在大于或等于60岁与小于60岁两年龄组间、男女组间、鳞状细胞癌组与腺癌组间及其分化程度以及c-erbB-2表达阳性组与阴性组间比较有显著性差异（P〈0．01）;而在有无淋巴结转移组间BRCA2蛋白表达阳性率比较无显著性差异（P〉0．05）;ER、PR在所有非小细胞肺癌病例中均为阴性。结论非小细胞肺癌可见BRCA2和c-erbB-2的表达,其两者的表达具有相关性,可能存在协同作用。提示BRCA2和c-erbB-2可作为反映非小细胞肺癌恶性特征的一个检测指标。     

Tissue microarray-based immunohistochemical study can significantly underestimate the expression of HER2 and progesterone receptor in ductal carcinoma in situ of the breast

Abstract

The accuracy of immunohistochemical (IHC) analysis on tissue microarray (TMA)-based studies largely depends on the uniformity of the staining pattern for a given antibody and minimal intratumor heterogeneity of a given tumor. Our study was designed to investigate the concordance of expression in TMA and whole sections of estrogen receptor (ER), progesterone receptor (PR) and HER2 using IHC analysis for ductal carcinoma in situ (DCIS) of the breast. Seventy-five consecutive cases of DCIS were retrieved, reviewed and used to construct the TMA. IHC analysis of the expression of ER, PR, and HER2 were performed on TMA and whole sections of the corresponding cases, and the results were compared. The specificity and sensitivity for TMA-based assays were 87.0, 75.9, 90.6 and 90.4%, and 76.1, 27.3 for ER, PR and HER2, respectively. The concordance and discordance were 89.3, 76.0 and 72.0%, and 6.7, 13.3 and 16.0% for ER, PR, HER2, respectively. The kappa values were 0.83, 0.89 and 0.42 for ER, PR and HER2, respectively. The non-concordance rates were inversely related to core number, with 46.67, 22.67 and 11.56% for one core, two cores, and three cores, respectively, per marker per case (p < 0.001), but not associated with tumor size. Our results showed that the intratumor heterogeneity and the number of cores have a great impact on the results of TMA-based studies. Increasing the number of tissue cores per case may help improve the accuracy and concordance with whole section results. Although TMA remains an effective tool for translational research, we should be cautious in our interpretation of these results.     

The prognostic value of hormone receptor detection by enzyme immunoassay and immunohistochemistry: a prospective study in patients with early breast cancer

The main reason to determine estrogen (ER) and progesterone receptors (PR) in breast cancer is their predictive value for the response to endocrine therapy. In addition, ER and PR are often used as prognostic indicators. Enzyme immunoassay (EIA) and immunocytochemical assay (ICA) are two methods for determining ER and PR. These two methods have not been compared with each other in relation to clinical endpoints. In the present study we prospectively evaluated the prognostic value of ER and PR as determined by ICA and EIA in 223 and 207 patients, respectively, with early breast cancer. ER was positive in approximately 77% of patients, while PR was positive in approximately 65% of patients. The proportion of potential agreement beyond chance between EIA and ICA was 0.58 and 0.65 for ER and PR, respectively. The median follow-up was 86 months. Both ER and PR appeared to be weak prognostic factors. There were no differences in prognostic value according to the time point of analysis or cutoff value chosen, nor were there any differences in the prognostic value of hormone receptors detected by ICA or EIA. Both methods appear to be equivalent in terms of qualification and prognostic value.