乳腺癌组织中AIB-1蛋白表达与临床病理指标的相关性

目的探讨乳腺癌组织中AIB-1的表达与临床病理指标的关系。方法采用免疫组织化学方法检测218例乳腺癌组织、45例正常乳腺组织、45例良性乳腺病变组织中AIB-1表达情况,并结合乳腺癌患者的临床病理资料进行统计分析。结果乳腺癌组织中AIB-1过表达率（54.59％）显著高于正常乳腺组织（22.22％）和乳腺良性病变组织（33.33％）（P=0.000）。AIB-1在乳腺癌组织学分级Ⅲ级组过表达率（63.39％）显著高于Ⅰ级组（18.18％）和Ⅱ级组（48.42％）（P=0.004）。AIB-1在腋淋巴结转移＞3个组中的过表达率（73.47％）显著高于腋淋巴结转移≤3个组（49.11％）（P=0.003）。乳腺癌组织中,AIB-1过表达率在ER阳性组（59.26％）、阴性组（46.99％）间的差异无统计学意义（P=0.077）,PR阳性组（59.48％）、阴性组（49.02％）间的差异无统计学意义（P=0.122）,而HER-2阳性组的AIB-1过表达率（64.08％）显著高于阴性组（46.08％）（P=0.008）。结论乳腺癌中AIB-1过表达与肿瘤的恶性程度密切相关,提示可能预后不良。AIB-1是一个重要的预测他莫昔芬疗效的指标。     

转移性乳腺癌循环肿瘤细胞的上皮间质转化水平对化疗疗效的预测意义

目的 检测转移性乳腺癌患者外周血循环肿瘤细胞（CTCs）不同亚型相关基因的表达,探讨其对化疗疗效的预测意义。方法 应用免疫磁性分选（MACS）技术联合逆转录 聚合酶链反应（RT-PCR）法检测58例转移性乳腺癌患者和10例健康人外周血中CTCs上皮型标志物上皮角蛋白（CK18、CK19）和间质型标志物（波形蛋白、纤连蛋白）mRNA的表达。分析上皮型标志物及间质型标志物表达与不同亚型乳腺癌之间的关系,并分别评估具有不同表型CTCs患者之间疗效的差异。结果 在10例健康志愿者的血液样本中,未检测出CK18、CK19、波形蛋白和纤连蛋白mRNA的表达。在58例转移性乳腺癌患者的血液样本中,检测出36例（62.1％）上皮角蛋白表达,19例（32.8％）间质型标志物表达。Luminal A组和HER-2阳性组的上皮型标志物阳性表达率高于三阴性乳腺癌组（P=0.008）,而间质型标志物阳性表达率则低于三阴性乳腺癌组（P＜0.001）。根据不同标志物的表达情况,将患者分为CKs+／EMT-组、CKs-／EMT-组、CKs+／EMT+组和CKs-／EMT+组,4组有效率依次为76.7％、55.6％、33.3％和15.4％,差异有统计学意义（P=0.002）。间质型标志物阴性者的化疗有效率高于间质型标志物阳性者（71.8% vs. 15.8%,P=0.000）。结论 转移性乳腺癌患者中部分CTCs将发生上皮间质转化而丢失上皮型细胞的表型,获得间质型细胞表型。间质型CTCs因具有更强的抵抗化疗药物的能力而存活,这可能是三阴性乳腺癌疗效不佳的原因之一。     

巨噬细胞移动抑制因子在骨肉瘤中的表达及其与预后的关系

目的 探讨巨噬细胞移动抑制因子（MIF）在骨肉瘤中的表达及其与临床病理特征和预后的关系。方法 应用免疫组化法检测61例骨肉瘤组织及15例癌旁组织（距肿瘤组织边缘＞5.0cm）中MIF表达,分析MIF表达与骨肉瘤临床病理特征之间的关系。采用Kaplan-Meier法计算生存情况,Cox多因素回归进行生存分析。结果 骨肉瘤组织中MIF阳性表达率为62.3％,癌旁组织为33.3％,差异有统计学意义（P=0.043）。MIF表达与骨肉瘤患者的性别、年龄、临床分期、组织分型无关,与肺转移相关（P=0.006）。MIF阳性表达组患者的3年生存率为70.3%,显著低于阴性表达组的95.8%（P=0.019）。Cox多因素回归分析显示,Enneking分期是影响患者预后的独立因素,而MIF表达非独立预后因素。结论 MIF表达与骨肉瘤转移密切相关,有助于评价骨肉瘤患者的预后。     

不同亚型乳腺癌脑转移临床特点及生存分析

目的探讨不同亚型乳腺癌脑转移的临床特点及预后。方法回顾性分析90例乳腺癌脑转移患者的临床资料,分为雌激素受体(ER)和(或)孕激素受体(PR)阳性,人表皮生长因子受体-2(HER-2)阳性和三阴性(ER、PR及HER-2均阴性)三种亚型。 结果90例患者中,ER和(或)PR阳性51例(56.7%)、HER-2阳性12例(13.3%)、三阴性27例(30.0%),中位无病生存期(30.9月、25.4月和16.0月,P=0.001)、无脑转移生存期(36.0月、38.0月和22.0月,P=0.008)之间差异有统计学意义,但总生存期(52.0月、25.5月和36.0月,P=0.075)及确诊脑转移后的生存期(11.0月、5.5月和8.0月,P=0.829)之间的差异无统计学意义。结论三阴性乳腺癌无病生存期明显缩短,更易于早期发生脑转移,但总生存期及确诊脑转移以后的生存期无明显差别。     

PIN1在胃癌组织中的表达及其预后意义

目的 探讨肽基脯氨酰顺反异构酶（PIN1）在胃癌中的表达及其与临床病理学特征及预后的关系。方法 应用组织芯片、免疫组化技术检测134例胃癌组织及对应癌旁组织中PIN1蛋白的表达情况,分析其与临床病理特征及预后的关系。结果胃癌组织中PIN1阳性表达率为33.6％（45／134）,癌旁组织为21.6％（29／134）,差异有统计学意义（P＜0.05）。PIN1表达与胃癌患者TNM分期和远处转移有关（P=0.007,P=0.010）,与其他临床病理特征无关（P＞0.05）。PIN1阳性患者的5年生存率为35.7％,阴性患者为50.6％,差异有统计学意义（P＜0.05）。Cox多因素分析显示,PIN1表达不是胃癌的独立预后因素,而pTNM分期和Lauren分型是胃癌的独立预后因素。结论 胃癌组织中存在PIN1阳性表达,并与TNM分期和远处转移及预后密切相关,可能是潜在的胃癌治疗靶点。     

CyclinA、C-myc在皮肤瘢痕及瘢痕癌组织中的表达及意义

目的探讨CyclinA、C-myc在皮肤病理性瘢痕和瘢痕癌组织中的表达及意义。方法以病理性皮肤瘢痕、皮肤瘢痕癌组织为研究对象,以正常皮肤组织为对照。采用免疫组织化学（SP法）分别检测CyclinA、C-myc蛋白的表达,采用核酸分子原位杂交法检测CyclinA mRNA的表达,所有数据输入计算机后运用SPSS 16.0软件包进行统计学分析。结果（1）CyclinA、CyclinA mRNA在正常皮肤和皮肤瘢痕上皮中的表达呈阴性或弱阳性,在瘢痕癌组织中呈强阳性。瘢痕癌组的表达（平均吸光度和阳性面积）与正常皮肤组及皮肤瘢痕组比较,差异均有统计学意义（P＜0.01）;但正常皮肤组与瘢痕组比较,差异无统计学意义（P>0.05）。（2）C-myc蛋白在正常皮肤中的表达呈弱阳性,在皮肤瘢痕上皮中呈阳性,在瘢痕癌组织中呈强阳性。且两两比较差异均有统计学意义（P＜0.05）。（3）相关分析显示,在皮肤瘢痕癌中,CyclinA 与CyclinA mRNA(r=0.766,P＜0.01)、CyclinA与C-myc蛋白(r=0.804,P＜0.01)的表达均呈正相关。结论（1）CyclinA及其mRNA、C-myc的高表达,可能与皮肤瘢痕癌的发生有关;（2）C-myc蛋白的高表达与皮肤瘢痕上皮癌变有相关性。（3）在瘢痕癌中CyclinA同时存在蛋白水平和基因水平的异常表达。     

雄激素受体在Her-2过表达型乳腺癌中的意义

摘 要：［目的］ 探讨雄激素受体（androgen receptor,AR）在人表皮生长因子受体-2（human epidermal growth factor receptor-2,Her-2）过表达型乳腺癌中的临床意义。［方法］ 用免疫组化方法检测有完整临床及随访资料的102例Her-2过表达型乳腺癌中AR表达,并分析其与临床病理特征及5年无疾病进展时间（disease-free survinal,DFS)的相关性。［结果］ AR在Her-2过表达型乳腺癌阳性率为75.5%（77/102）;淋巴结阴性组AR表达率为84.91%（45/53）,明显高于淋巴结阳性组的65.31%（32/49）(χ2=5.286,P=0.021);Ki-67阴性组AR表达率（89.47%,34/38）明显高于Ki-67阳性组的67.19%（43/64）(χ2=6.400,P=0.011）。生存分析显示,AR阳性组5年无瘤生存率为71.7%,明显低于AR阴性组的89.8%(χ2=5.736,P=0.017）。Cox回归分析显示,AR是影响Her-2过表达型乳腺癌5年DFS的独立预后因素（RR=3.961,95%CI：1.008~15.574）。［结论］ AR在Her-2过表达型乳腺癌中的表达率高,AR阳性患者预后较差,AR可能成为Her-2过表达型乳腺癌新的治疗靶点。     

雄激素受体在三阴性乳腺癌组织中的表达及其与临床病理特征及预后的相关性

目的:检测雄激素受体（AR）在三阴性乳腺癌（TNBC）组织中的表达情况,及其与临床病理特征及预后的相关性。方法:选取2012年至2016年间101例经病理确诊三阴性乳腺癌患者肿瘤组织标本,通过免疫组化法(IHC)检测肿瘤组织雄激素受体（AR）表达状况,分析AR表达与不同临床病理参数及预后的相关性。结果:在101例TNBC患者中,AR表达阳性患者27例(26.7%),AR表达阴性患者74例(73.3%)。AR阳性TNBC较AR阴性TNBC更多表现为非浸润性导管癌（P=0.015）和较低的组织学分级（I/II,P=0.000）及低Ki-67表达(P=0.010)。AR阳性较AR阴性TNBC患者具有较好的无病生存期及总生存期(P=0.014,P=0.021)。单因素回归分析显示,AR阴性表达、高的组织学分级、肿瘤直径大于2 cm与不良的无进展生存期显著相关（P＜0.05）;AR阴性表达、高的组织学分级、肿瘤直径大于2 cm与不良的总生存期显著相关（P＜0.05）。多因素Cox回归分析显示,AR阳性表达为判断TNBC患者良好无进展生存期及良好总生存期的独立因素（P＜0.05）。结论:AR表达与多种临床病理因素存在相关性,AR表达对TNBC患者预后有显著影响,AR可能在三阴性乳腺癌靶向治疗中具有重要作用。     

间皮素在乳腺癌中的表达及其临床意义

目的 研究间皮素（MSLN）在乳腺癌组织中的表达及其与临床病理特征的关系。方法 收集56例手术切除的乳腺癌组织及其相应的癌旁组织标本,应用免疫组化法分别检测乳腺癌组织和癌旁组织中MSLN的表达情况。结果 56例乳腺癌组织的MSLN阳性表达率为42.9％ （24／56）,高于癌旁组织的10.7％（6／56）,差异有统计学意义（P＜0.05）。MSLN的表达与乳腺癌患者的肿瘤分化程度、肿瘤大小及雌激素受体（ER）表达相关（P＜0.05）,肿瘤直径较大、中低分化及ER阴性者的MSLN阳性表达率高;MSLN的表达与年龄、有无淋巴结转移及人表皮生长因子受体（HER-2）表达情况均无关（P＞0.05）。 结论 检测MSLN在乳腺癌组织中的表达有助于乳腺癌的诊断,并可作为判断其恶性程度的重要指标。     

瘦素和瘦素受体在乳腺癌组织中的表达及其与临床预后的关系

目的　检测瘦素（ＯＢ）和瘦素受体（ＯｂＲ）在人乳腺癌组织中的表达情况,探讨二者与ＨＥＲ-２以及临床病理之间的关系,并分析它们对预后的影响。方法　用免疫组织化学的方法检测１１４例乳腺癌组织中ＯＢ和ＯｂＲ的表达,回顾分析相关的临床病理资料和随访情况。结果　ＯＢ和ＯｂＲ在大多数乳腺癌组织中均有表达,阳性率分别为７９.８％和８５.１％;ＯＢ和ＯｂＲ的表达与患者的年龄、绝经状态、肿瘤大小、肿瘤病理学分型、淋巴结转移及远处转移均无关（Ｐ＞０.０５）;与ＥＲ、ＰＲ、ｐ５３的表达状态也无关（P＞０.０５）;ＯｂＲ的表达与ＨＥＲ-２相关（P＝０.０１８）;ＯＢ阳性者的总生存时间（ＯＳ）短（Ｐ＝０.００９）;在亚组分析中,绝经后、三阴乳腺癌和淋巴结转移组中ＯＢ阳性的ＯＳ均短于ＯＢ阴性（P分别为０.０３８、０.００６和０.００４）。结论 ＯｂＲ与ＨＥＲ-２在乳腺癌中的表达具有相关性,ＯＢ可能是导致乳腺癌预后不良的因素。     

Expression of androgen receptor in breast cancer and its significance as a prognostic factor

BackgroundBreast cancer is an extraordinarily hormone-dependent tumor. This study was to evaluate androgen receptor (AR) status and its significance in breast cancer in Chinese women.MethodsThree hundred and thirty-five consecutive cases of invasive ductal breast carcinoma, 34 ductal carcinoma in situ (DCIS), and 82 DCIS adjacent to invasive tissues were involved in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient outcome, and its implications were evaluated in five molecular subgroups of invasive ductal carcinoma (IDC) and in DCIS lesions.ResultsAR expression was related to that of estrogen receptor (P < 0.001) and progesterone receptor (P = 0.035) but not correlated with the other conventional parameters. AR retained independent prognostic significance (hazard ratio 0.309, 95% confidence interval, 0.192–0.496; P < 0.001). The majority (61.0%) of basal-like breast cancers showed loss of AR expression (P < 0.001), which had poor prognosis. The percentage of AR-positive cases was significantly higher in DCIS adjacent to IDC group than in pure DCIS and IDC groups (93.9%, 79.4%, and 72.5%; P = 0.046 and P < 0.001, respectively).ConclusionsOur data suggest that AR may provide another specific definition of breast cancer subtypes and reveal a potential role in DCIS progression. These findings may help develop new therapies.     

A Functionally Significant Cross-talk between Androgen Receptor and ErbB2 Pathways in Estrogen Receptor Negative Breast Cancer

Recent studies have identified novel subgroups in ER-negative breast cancer based on the expression pattern of androgen receptor (AR). One subtype (molecular apocrine) has an over-expression of steroid-response genes and ErbB2. Using breast cancer cell lines with molecular apocrine features, we demonstrate a functional cross-talk between AR and ErbB2 pathways. We show that stimulation of AR and ErbB2 pathways leads to the cross-regulation of gene expression for AR, ErbB2, FOXA1, XBP1, TFF3, and KLK3. As opposed to the physiologic transient phosphorylation of extracellular signal-regulated kinase (ERK1/2) observed with the testosterone treatment, we demonstrate that the addition of ErbB2 inhibition leads to a persistent phosphorylation of ERK1/2, which negatively regulates the downstream signaling and cell growth. This suggests a mechanism for the cross-talk involving the ERK pathway. Moreover, testosterone stimulates the proliferation of molecular apocrine breast cell lines, and this effect can be reversed using antiandrogen flutamide and anti-ErbB2 AG825. Conversely, the growth stimulatory effect of heregulin can also be inhibited with flutamide, suggesting a cross-talk between the AR and ErbB2 pathways affecting cell proliferation. Importantly, there is a synergy with the combined use of flutamide and AG825 on cell proliferation and apoptosis, which indicates a therapeutic advantage in the combined blockage of AR and ErbB2 pathways.     

雄激素受体在三阴乳腺癌的表达及临床意义

Background and Objective:Androgen receptor(AR) is involved in the pathogenesis of breast cancer,but its role is not clearly defined.This study was to explore the expression of AR and its relationship with clinicopathologic parameters in triple negative breast cancer(negative estrogen receptor,negative progesterone receptor,and negative Her-2).Methods:Immunohistochemical assays were performed to determine the expression of AR in 137 cases of triple negative breast cancer and 132 cases of non-triple negative ...     

Identification of molecular apocrine breast tumours by microarray analysis

Previous microarray studies on breast cancer identified multiple tumour classes, of which the most prominent, named luminal and basal, differ in expression of the oestrogen receptor alpha gene (ER). We report here the identification of a group of breast tumours with increased androgen signalling and a 'molecular apocrine' gene expression profile. Tumour samples from 49 patients with large operable or locally advanced breast cancers were tested on Affymetrix U133A gene expression microarrays. Principal components analysis and hierarchical clustering split the tumours into three groups: basal, luminal and a group we call molecular apocrine. All of the molecular apocrine tumours have strong apocrine features on histological examination (P=0.0002). The molecular apocrine group is androgen receptor (AR) positive and contains all of the ER-negative tumours outside the basal group. Kolmogorov-Smirnov testing indicates that oestrogen signalling is most active in the luminal group, and androgen signalling is most active in the molecular apocrine group. ERBB2 amplification is commoner in the molecular apocrine than the other groups. Genes that best split the three groups were identified by Wilcoxon test. Correlation of the average expression profile of these genes in our data with the expression profile of individual tumours in four published breast cancer studies suggest that molecular apocrine tumours represent 8-14% of tumours in these studies. Our data show that it is possible with microarray data to divide mammary tumour cells into three groups based on steroid receptor activity: luminal (ER+ AR+), basal (ER- AR-) and molecular apocrine (ER- AR+).     

ER和PR阴性乳腺癌雄激素受体与HER2表达相关性及其临床意义

目的 激素受体阴性(ER-/PR-)乳腺癌具有明显的肿瘤异质性,临床治疗手段相对有限.本研究探讨激素受体阴性乳腺癌组织中,雄激素受体(androgen receptor,AR)和HER2表达的相关性,及其与临床病理参数和预后的相关性.方法 收集中国人民解放军福州总医院经手术治疗并病理确诊的乳腺癌120例,中位年龄52岁.采用FISH法检测收集的激素受体阴性乳腺癌组织HER2/neu基因状态,分为HER2阳性(HER2过表达组)和HER2阴性(三阴组)两组,每组60例.并采用EliVisionTM plus免疫组化法检测AR、Ki-67、EGFR表达,分析HER2和AR表达与临床病理参数、3年无病生存期(disease free survival,DFS)的相关性.结果 AR在激素受体阴性乳腺癌组织阳性率为61.67％(74/120),HER2过表达组和三阴组分别为73.33％(44/60)和50.00％(30/60).激素受体阴性乳腺癌组织中,AR表达与月经状态、肿瘤大小、组织学分级、EGFR表达及HER2状态相关,均P值＜0.05;在HER2过表达组中,AR表达与月经状态、淋巴结受累、EGFR表达相关,均P值＜0.05;三阴组中,AR表达与肿瘤大小和组织学分级相关,均P值＜0.05.Kaplan-Meier法分析显示,HER2过表达组中AR表达与患者的3年DFS呈正相关,P＜0.05;Cox回归法分析结果示,肿瘤大小、淋巴结受累、EGFR表达、AR表达均与患者的3年DFS有关,P＜0.05.结论 AR可能成为筛选激素受体阴性乳腺癌高危人群和预测其预后的辅助指标之一,可作为激素受体阴性乳腺癌的新治疗靶点,为不同HER2状态乳腺癌治疗提供新思路.     

Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers

The purpose of this article is to evaluate the prognostic value of androgen receptor (AR) expression in patients with estrogen receptor (ER)-positive breast cancer, treated with endocrine therapy, with or without the addition of chemotherapy. A consecutive series of 953 patients with ER-positive breast cancer, treated between 1998 and 2003, was selected. Repeated immunohistochemistry confirmed the expression of ER in the tumor of 938 patients. AR expression was measured by immunohistochemistry. The Kaplan–Meier method, logrank test and multivariate Cox models were used to explore the impact of AR expression on time to relapse (TTR) and disease specific survival (DSS) in all patients and in subgroups treated with chemo-endocrine therapy or endocrine therapy alone. AR immunoreactivity was assessable in 859 tumors and positive in 609 (70.9%). AR expression was a significant marker of good prognosis for TTR (P = 0.001) and DSS (P < 0.001). This effect was particularly evident in the group of patients receiving chemo-endocrine therapy (TTR (P = 0.015) and DSS (P < 0.001)). Cox models confirmed AR as an independent variable for both TTR (P = 0.003, HR 0.444, 95%CI 0.258–0.765) and DSS (P < 0.001, HR 0.135, 95%CI 0.054–0.337). Thus, we focused on ER-positive luminal B breast cancer that may be selected for chemotherapy because of their more aggressive immunophenotype. In this subset AR expression identified a group of patients with better prognosis for TTR (P = 0.017, HR 0.521, 95%CI 0.306–0.888) and DSS (P = 0.001, HR 0.276, 95% CI 0.130–0.588). AR expression is an independent prognostic factor of better outcome in patients with ER-positive breast cancers.     

The expression and clinical significance of the androgen receptor and E-cadherin in triple-negative breast cancer

Triple-negative breast cancer (TNBC) has a poor prognosis and lacks prognostic indicators. The androgen receptor (AR) and E-cadherin are involved in the pathogenesis of breast cancer, but their roles are not clearly defined. We designed this study to evaluate AR and E-cadherin expression and to determine their relationships with the clinicopathologic parameters of triple-negative breast cancer. The present study included 127 TNBC patients. Immunohistochemical stains for AR and E-cadherin were performed, and the relationships between AR and E-cadherin expression and clinicopathologic data and prognosis were analyzed. We found that in TNBC patients, AR was expressed in 16(12.6%) cases, and E-cadherin was expressed in 41(33.0%) cases. AR expression was associated with tumor grade (P = 0.004) and menopausal status (P = 0.017), and E-cadherin expression was associated with node status (P= 0.016). A multivariate analysis demonstrated that tumor size, tumor grade, lymph node status, and E-cadherin were of prognostic significance for disease-free interval and overall survival. Compared with AR-positive patients, AR-negative patients showed significantly poorer outcomes with respect to the disease-free interval (P = 0.047) and overall survival (P = 0.038). E-cadherin-negative patients experienced shorter disease-free interval (P = 0.016) and poorer overall survival (P = 0.012) than did E-cadherin-positive patients. An AR-positive and E-cadherin-negative expression profile was associated with recurrence or metastasis (P = 0.036). Moreover, as the expression of nuclear AR increased (25% vs. 33.3%, P = 0.361), less E-cadherin staining was observed in TNBC samples. This finding suggested that AR and E-cadherin expression could be a useful prognostic marker for classifying subgroups of TNBC.