婚姻状况对妇女乳腺癌ER、PR表达的影响

为了探讨精神压力能否通过神经内分泌机制促进乳腺癌的发生和发展,本文运用免疫组化技术,对比离婚妇女和现婚妇女乳腺癌的雌激素受体和孕激素受体的表达情况。结果发现,离婚组乳腺癌ＥＲ和ＰＲ表达率均高于现婚组。说明精神因素与ＥＲ表达之间存在着一定内在关系。     

乳腺癌ER,PR状态与细胞超微结构变化的形态定量分析

用免疫组化ＰＡＰ法检测３０例乳腺癌雌激素受体（ＥＲ）和孕激素受体（ＰＲ），从中选取ＥＲ、ＰＲ阳性者（Ｅ＾＋Ｐ＾＋）６例，阴性者（Ｅ＾－Ｐ＾－）５例作透射电镜观察，对部分细胞器连接的变化进行形态定量分析。结果Ｅ＾－Ｐ＾－组癌细胞内线粒体、粗面内质网及溶酶体的含量明显高于Ｅ＾＋Ｐ＾＋组，且差异有显著性（Ｐ＜０．０５，０．０１，０．０１）；Ｅ＾－Ｐ＾－组细胞间的桥粒及镶嵌连接有减少趋势，但差异无显著性     

喉癌组织ER及PR免疫组化检测研究

通过ＡＢＣ法对６０例喉癌组织及２５例非癌喉组织（包括１０例正常喉组织，１０例声带息肉组织，５例喉鳞状细胞乳头状瘤组织）进行雌激素受体及孕激素受体检测。结果发现：喉癌组织的ＥＲ及ＰＲ阳性率分为８０％及６５％，而非癌喉组织的ＥＲ阳性率仅４％。ＰＲ全部阴性，差异有显著性，阳性率与喉癌的组织学分级成反比，且在染色程度上有明显差别，与年龄成正比，本文对ＥＲ及ＰＲ的存在与喉癌发病的关系作初步探讨。认为本课题有     

乳腺癌术前巴德枪穿刺检测ER、PR的临床研究

目的 探讨乳腺癌术前巴德枪穿刺活检检测 ER、PR在乳腺癌治疗中的临床应用价值。方法 选取山东省济南市市中区人民医院外科2013年12月~2015年12月36例乳腺癌患者,术前采用巴德枪穿刺获得病理组织,并进行免疫组织化学检测,与术后常规病理免疫组织化学检测结果进行对比。结果 36例乳腺癌患者术前巴德枪穿刺病理组织行免疫组织化学检测结果与术后常规病理检测结果对比发现,ER表达程度差异无统计学意义（P＞0.05）;PR表达程度差异有统计学意义（P＜0.05）。结论 术前巴德枪穿刺获得的组织经免疫组织化学检测可以反映乳腺癌ER、PR的表达以及表达强度,但是PR表达强度却高于术后常规免疫组织化学检测结果,提示采用术前巴德枪穿刺组织检测的PR作为评估内分泌治疗对乳腺癌PR表达的影响时,应考虑与术后常规免疫组织化学检测结果的差异。     

计算机定量辅助在乳腺癌ER、PR表达判读一致性中的应用

目的 比较计算机定量辅助判读ER、PR阳性率和染色强度与人工判读的一致性。方法 收集100例乳腺浸润性导管癌标本,先由三位病理医师对100例乳腺浸润性导管癌中ER、PR阳性率和染色强度进行判读;再由三位诊断水平相近的病理医师应用计算机定量辅助显微镜进行判读,分别计算两组阳性率的组内相关系数(intraclass correlation coefficient, ICC)和染色强度的Fleiss Kappa值。结果 三位病理医师采用人工判读ER、PR阳性率的ICC为0.943(95%CI:0.920～0.960)、0.946(95%CI:0.930～0.960)(P<0.01);ER、PR染色强度的Kappa值为0.592(95%CI:0.519～0.665)、0.482(95%CI:0.411～0.552)(P<0.01)。另三位病理医师采用计算机定量辅助判读ER、PR阳性率的ICC为0.980(95%CI:0.970～0.990)、0.977(95%CI:0.970～0.980)(P<0.01);ER、PR染色强度的Kappa值为0.692(95%CI:0.622～...     

在石蜡切片中检测ER、PR的体会

检测组织切片上某些肿瘤细胞的雌激素受体（ＥＲ）、孕激素受体（ＰＲ），对指导临床内分泌治疗及推测肿瘤预后有重要意义。如何成功地检测肿瘤细胞内的ＥＲ、ＰＲ受体，是广大病理工作者最为关心的问题。一些医院由于种种原因，致使在染色过程中达不到理想的结果。针对存...     

用改良LSAB法检测乳腺癌雌激素受体和孕激素受体

用改良ＬＳＡＢ法检测乳腺癌雌激素受体和孕激素受体唐建林，高东宸乳腺癌雌激素受体（ＥＲ）和孕激素受体（ＰＲ）检测已经成为估计乳腺癌预后和内分泌治疗效果的主要方法。我们的实验以结合于ＥＲ，ＰＲ上的内源性激素为检测目标，以抗激素抗体为第一抗体，采用ＬｓＡＢ...     

乳腺癌石蜡切片中显示雌,孕激素受体方法和阳性结果判断标…

为了探索雌，孕激素受体的检测方法和阳性结果判断标准的规范化，应用ＥＲ，ＰＲ单克隆抗体免疫组化Ｓ－Ｐ法检测乳腺癌石蜡切片中ＥＲ，ＰＲ的表达。结果显示：２００例ＥＲ及ＰＲ的阳性率分别为７３．５％及６５．５％。用单克隆抗体可直接显示ＥＲ，ＰＲ，结果可靠，敏感性高，重复性好，且与目前国际通用方法接轨。     

雌,孕激素受体免疫组化检测方法的选择和比较

目前已证实肿瘤组织中雌激素受体（ｅｓｔｒｏｇｅｎｒｅｃｅｐｔｏｒ，ＥＲ）和孕激素受体（ｐｒｏｇｅｓｔｏｇｅｎｒｅｃｅｐ－ｔｏｒ，ＰＲ）水平的检测作为一种肿瘤细胞的分化标记对乳腺癌、妇科肿瘤等的预后估计和指导内分泌治疗有重要意义。本实验通过常用的两种免...     

ER,PR and HER2 testing in breast cancer

The application of targeted therapies has played important roles in the improvement of breast cancer survival rate during the past two decades. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are well established biomarkers for breast cancer prognosis and for guiding treatment. Emerging data furthers our understanding of the biomarkers and their validity as predictive and prognostic indicators. Breast cancer biomarker testing guidelines have been recently updated. There are still several key challenges in the evaluations of these markers, including pre-analytic standards, tissue selection for testing and re-testing, result interpretations, and tumour heterogeneity. In addition to ER, PR and HER2, newer markers and multigene testings may provide additional information in guiding targeted therapy for breast cancer.     

90例乳腺良性病变组织中ER和PR的表达

应用免疫组化方法对９０例良性乳腺病变组织进行ＥＲ、ＰＲ的检测。结果，ＥＲ阳性率为８４．４％，ＰＲ为８３．３％，与同期乳腺癌的ＥＲ和ＰＲ阳性率比较有非常显著性意义，ＥＲ阳性以纤维腺瘤，导管内乳头状瘤，囊性乳腺增生症最为常见，小叶内增生ＥＲ阳性相对减少，同时对乳腺组织间质存在前背景染色问题加以讨论。     

SHP2 is up-regulated in breast cancer cells and in infiltrating ductal carcinoma of the breast, implying its involvement in breast oncogenesis

Aims: To determine whether Src homology phosphotyrosyl phosphatase 2 (SHP2) is up‐regulated in breast cancer and, if so, to determine whether its up‐regulation has any relationship with clinical variables of breast cancer. Methods and results: Immunoblotting, immunohistochemistry and immunofluorescence microscopy were used to assess the state of SHP2 expression in breast cancer cells and in infiltrating ductal carcinoma (IDC) of breast. The possible role of SHP2 in breast cancer cell transformation was determined by dominant‐negative expression and anchorage‐independent growth assays. All of the breast cancer cell lines tested and 72% of IDC breast tumours analysed had increased amounts of the SHP2 protein. In support of its positive role, dominant‐negative SHP2 blocked anchorage‐independent growth of breast cancer cells. Furthermore, overexpression of SHP2 seemed to have a positive relationship to HER2 overexpression, nuclear accumulation of hormone receptors, higher tumour grade and lymph node metastasis, but not to age of breast cancer patients. Conclusion: SHP2 is a widely overexpressed signalling protein in IDC breast tumours. Given SHP2’s positive role in cell growth, transformation and stem cell survival, the positive relationship of its overexpression to lymph node metastasis, nuclear accumulation of hormone receptors and higher tumour grade suggests that SHP2 promotes breast oncogenesis.     

乳腺癌中ERα、PR的表达与预后关系及其影响阳性率的相关因素

目的分析乳腺癌中ERα、PR的阳性率与预后的关系,探讨影响ERα、PR阳性率的相关因素。方法采用免疫组化En Vision法检测662例乳腺癌组织中ERα、PR的表达,按不同阳性率分组,Kaplan-Meier法分析预后。选择其中的80例采用两种克隆号ERα(SP1、6F11)染色并由一位高年资医师判读,以分析不同克隆号对阳性率的影响;选择其中的214例ERα(SP1)由三位不同年资医师采用Allred score、H score两种判读系统分别判读,以观察不同判读系统及医师经验对阳性率的影响。一致性采用Kappa检验。结果生存分析显示,ERα、PR低阳性组无病生存率(disease-free survival,DFS)、总生存率(overall survival,OS)均优于阴性组(DFS:P=0.021、0.003)、(OS:P=0.019、0.003),ERα、PR高阳性组DFS、OS均优于低阳性组(DFS:P=0.011、0.002)、(OS:P=0.012、0.005)。浸润性癌非特指型、浸润性小叶癌、导管原位癌ERα阳性率分别为59.5%、78.9%、63.6%,差异有统计学意义(P=0.002),PR阳性率分别为56.3%、68.9%、59.1%,差异无统计学意义(P=0.079)。不同组织学分级的浸润性癌非特指型ERα、PR阳性率差异有统计学意义(P均0.001)。不同核级导管原位癌ERα、PR阳性率差异有统计学意义(P均0.05)。克隆号SP1阳性细胞百分率、染色强度均优于6F11;判读系统H score重复性略优于Allred score;高年资医师间阳性细胞百分率、染色强度判读重复性好(κ=0.850,κ=0.824),而高年资和低年资医师之间重复性均较差(0.4κ0.75);阳性细胞百分率估计法与计数法重复性较差(κ=0.726)。结论 ERα、PR不同阳性细胞百分率与患者预后密切相关,影响ERα、PR阳性率的因素包括病理类型、组织学分级、核分级、抗体的选择、判读系统及判读医师间的差异等。     

A study to determine the incidence of estrogen receptor (ER) and progesterone receptor (PR) expression in different histological grades of breast cancer

Abstract

Carcinoma of the breast is the most common non-skin malignancy in women and second most common cause of death due to cancer in females. Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. This study was conducted with the aim of analysis of steroid receptor status in breast cancer and its association with other prognostic factors of breast cancer such as histological grade, tumor size, and axillary lymph node status. Fifty patients with the diagnosis of breast cancer were included in this study. Detailed clinical and histopathologic data were recorded in all cases. Estrogen receptor (ER) and progesterone receptor (PR) status was evaluated by immunohistochemistry. Histological grading was done with Nottingham modification of the Bloom and Richardson method. Fisher’s exact test and chi-square test was used for statistical analysis. On immunohistochemical staining, 44% cases proved to be ER positive and 48% cases PR positive. The results from the present study in India documented low ER and PR positivity in breast cancer in comparison to results from the western world. An inverse relation was found between hormone receptor (HR) status and histological grading, but no statistically significant relationship was noted between HR expression and tumor size and lymph node status.     

三阴型乳腺癌中RHBDD1和EGFR的表达及相关性分析

目的探讨RHBDD1和EGFR在三阴型乳腺癌(triple negative breast cancer, TNBC)发生、转移中的作用及其临床意义。方法选取30例TNBC(ER、PR、HER2均阴性)和30例非三阴型乳腺癌(non triple negative breast cancer, NTNBC)(ER、PR、HER2至少一项阳性)患者作为研究对象,采用免疫组化、酶联免疫法和qRT-PCR技术检测组织和血清中RHBDD1和EGFR mRNA含量及蛋白表达。结果 TNBC组织中RHBDD1和EGFR蛋白阳性率(83%、80%)高于NTNBC组织(67%、37%),差异均有统计学意义(P<0.05);TNBC患者血清中RHBDD1和EGFR的浓度含量亦明显高于NTNBC患者,差异均有统计学意义(P<0.05);TNBC组织中的RHBDD1 mRNA和EGFR mRNA含量分别是癌旁组织的3.68倍和4.56倍,差异均有统计学意义(P<0.05)。RHBDD1和EGFR的表达与TNBC患者年龄无关,与临床分期、组织学分级、肿瘤大小、淋巴结转移以及远处转移呈正相关。...     

Estrogen receptor (ER), progesterone receptor (PR), and HER2 expression pre- and post- neoadjuvant chemotherapy in primary breast carcinoma: a single institutional experience

Background

The estrogen receptor (ER), progesterone receptor (PR), and HER2 profile of a primary breast carcinoma plays a significant role in patient management and treatment. Because of the increasing utilization of neoadjuvant chemotherapy or hormone therapy, surgically-resected carcinomas often show marked treatment effect. The aim of this study was to compare immunohistochemical (IHC) profiles (ER, PR, HER2, HER2 FISH) of primary breast carcinomas before and after neoadjuvant chemotherapy to assess the subsequent effects on hormone receptor status.

Design

Primary breast carcinomas from 38 female patients treated with neoadjuvant therapy after needle core biopsy or fine needle aspiration diagnosis were included. Histologic data was collected for each case, including site, type, grade, tumor size (cm), pre- and post- neoadjuvant treatment IHC panel (ER, PR, HER2), and fluorescence in-situ hybridization (FISH) for HER2.

Results

Of the 38 carcinomas studied, 45 % were positive for ER by IHC both pre- and post- neoadjuvant treatment (P=1.00). IHC studies for PR in these 38 patients showed 37% positivity for PR pre-neoadjuvant therapy and 21% positivity post-treatment (p=0.03). For 37 patients with HER2 IHC, 32% were positive pre-treatment, and 22% were positive post-treatment (P = 0.20). For 7 patients, HER2 FISH was positive in 71% pre-therapy and in 57% post-treatment (P=0.32).

Conclusions

Profiles for ER, HER2 IHC, and HER2 FISH were not significantly different in primary breast carcinomas before and after neoadjuvant chemotherapy. Further investigation is warranted to assess reproducibility of technique and investigate clinical implications of significant loss of PR status in treated patients.     

Evaluation of BrightGen HR RT-qDx assay to detect nuclear receptors mRNA overexpression in FFPE breast cancer tissue samples for selection of tamoxifen therapy

Breast cancer is a significant cause of death in women. Estrogen receptor (ER) and progesterone receptor (PR) are important prognostic factors indicating higher recovery rate in the breast cancer patients. Currently, immunohistochemical (IHC) staining is a conventional method to identify expression of ER and PR. If a breast cancer patient expresses ER or PR, a chemotherapy with estrogen inhibitors such as tamoxifen is supposed to be effective. Although IHC staining is a reliable method, it may not a useful method for continuous monitoring of ER and PR expression changes in multiple breast cancer patients. In the present study, we evaluated an alternative method of IHC for detection of ER and PR expression. A quantitative RT-PCR method called ‘the BrightGen HR RT-qDx assay’ was employed to detect mRNA expression of the nuclear receptors in 199 formalin-fixed paraffin-embedded (FFPE) breast cancer tissue samples. Among the ER/PR positive samples by IHC, 83 were determined positive and 16 were determined negative for the nuclear receptor mRNA by the quantitative RT-PCR method. Among the ER/PR negative samples by IHC, 37 were determined negative and 2 were determined positive by the quantitative RT-PCR method. The overall sensitivity and specificity of the quantitative RT-PCR method were 83.8% and 94.8% (P = 0.0026), respectively. We also optimized the quantitative RT-PCR method by setting up the diagnostic cut-off value using the likelihood ratio. The highest likelihood ratio was when the expression levels of the relative nuclear receptor mRNA passed 103.3 at which sensitivity and specificity was highest. These data suggest that BrightGen HR RT-qDx assay could be an alternative method for detection of the prognostic factors of nuclear receptors expressed in breast cancer patients for providing essential information for therapeutic application of tamoxifen.     

乳腺癌复发转移灶与原发灶中ER、PR、HER-2、p53、Ki-67的表达差异

目的 探讨ER、PR、HER-2、p53、Ki-67在乳腺癌复发转移灶与原发灶中的表达差异。方法 采用免疫组化En Vision两步法检测156例乳腺癌原发病灶及对应的复发或转移灶中ER、PR、HER-2、p53及Ki-67的表达,比较各指标的表达差异,并分析发生局部复发或远处转移的乳腺癌临床病理特征及与原发癌相比与各指标表达的一致性。结果 乳腺癌局部复发组和远处转移组与肿瘤分期(P=0.015)、肿瘤直径(P=0.005)差异有显著性;与患者年龄、组织学分级和腋窝淋巴结状态的差异无显著性(P0.05)。复发转移灶ER、PR阳性率比原发灶均有所下降,但差异无显著性;ER、PR表达不一致(分别为18.6%、19.2%),差异有显著性(P=0.024,P=0.043);原发灶与复发转移灶HER-2表达有较高的一致性,表达不一致占5.1%;原发灶与复发转移灶p53的阳性率差异不大,p53表达不一致占14.1%;复发转移灶Ki-67高表达者比原发灶多,Ki-67表达不一致占30.8%,差异有显著性(P0.001)。局部复发组和远处转移组各指标表达不一致的差异无显著性。结论 乳腺癌原发灶与复发转移灶ER、PR和Ki-67表达存在不一致性,HER-2表达有较高一致性。因此,检测乳腺癌复发转移灶中各指标表达对治疗方案选择和预后有重要意义。     

Pathological, clinical and prognostic characteristics of breast cancer in Central Sudan versus Northern Italy: implications for breast cancer in Africa

Aims:  In patients of Black African ethnicity, breast cancer is reportedly characterized by aggressive, poorly differentiated phenotype(s). To highlight possible differences between breast cancer in indigenous sub-Saharan African and European patients, two breast cancer case series, from Central Sudan (Khartoum) and Northern Italy (Milan), were compared for clinicopathological characteristics, expression of oestrogen receptor (ER), progesterone receptor (PR), Her-2/neu, basal cytokeratin (CK) 5/6 and CK17, and breast cancer subtypes.
Methods and results:  After careful antigen retrieval, 114 and 138 consecutive formalin-fixed paraffin-embedded (FFPE) breast cancer cases from the Radiation and Isotope Centre (Khartoum) and from MultiMedica (Milan), respectively, were screened by immunohistochemistry for ER, PR, Her-2/neu, CK5/6 and CK17. Compared with the Italian patients, the Sudanese patients were younger ( P  < 0.0001) and their tumours were larger ( P  < 0.0001), more advanced in stage ( P  < 0.00001), higher grade ( P  < 0.00001) and more frequently positive for nodal metastases ( P  < 0.00001). ER expression varied between the two series ( P  < 0.0008), but no significant differences were found for PR ( P  < 0.32), combined hormone receptors ( P  < 0.12), Her-2/neu ( P  < 0.09), CK5/6 ( P  < 0.1), CK17 ( P  = 0.4), combined basal CK status ( P  = 1) or breast cancer subtypes ( P  = 0.12).
Conclusion:  The differences between the Sudanese and Italian breast cancer series reflect stage at diagnosis rather than intrinsic biological characteristics. This may have relevant implications for breast cancer prevention and treatment in Africa.