Tissue microarray analysis of eIF4E and its downstream effector proteins in human breast cancer

Correction to Kleiner HE, Krishnan P, Tubbs J, Smith M, Meschonat C, Shi R, Lowery-Nordberg M, Adegboyega P, Unger M, Cardelli J et al : Tissue microarray analysis of eIF4E and its downstream effector proteins in human breast cancer. J Exp Clin Cancer Res 2009, 28:5.     

Lack of prognostic significance of nm23 expression in human primary breast cancer

This retrospective study was designed to evaluate the prognostic value of immunohistochemically detected nm23-expression in invasive breast cancer. Cellular expression of nm23 was assessed in 325 primary breast cancer tissues by immunohistochemistry. The data were correlated to established functional factors of prognosis (age, tumor size, nodal status, tumor grade, steroid hormone receptor status), and to clinical follow-up (median observation time, 92 months). 215/325 (66.2%) tumor tissues were considered nm23 positive. nm23 expression did not correlate to any of the investigated markers. Similar results were obtained after subdivision of the patients into node-negative patients (n=153) and node-positive cases (n=172). With respect to clinical outcome, nm23 expression displayed no statistical significance to predict the clinical course. In conclusion, the determination of nm23 expression is an independent factor but lacks prognostic or predictive value in breast cancer patients.     

CHIP在乳腺癌组织中的表达及其临床意义

目的 探讨Hsc70羧基末端反应蛋白（CHIP）在乳腺癌组织中的表达及其与临床病理特征、分子分型的关系。方法 采用免疫组化检测128例乳腺癌组织中CHIP蛋白的表达,分析CHIP表达与临床病理特征以及与不同分子分型乳腺癌的关系。结果 乳腺癌组织中CHIP阳性表达率为60.2%,Ⅲ、Ⅳ期乳腺癌患者CHIP阳性表达率为43.2%,显著低于Ⅰ、Ⅱ期的67.0%;伴有淋巴结转移者CHIP阳性表达率显著低于无淋巴结转移者,差异有统计学意义（P＜0.05）; Luminal A型、Luminal B型、HER-2型、Basal-like型中CHIP阳性表达率分别为66.7%、70.5%、50.0%和44.0%,差异亦具有统计学意义（P＜0.05）。CHIP表达与年龄、组织学分级、肿瘤大小、有无远处转移及HER-2表达等无关。结论 乳腺癌CHIP表达与肿瘤发生发展密切相关,并可能作为预测患者复发风险的指标。     

乳腺癌组织中survivin、c-erbB-2基因的表达与预后的关系

目的:探讨乳腺癌组织中survivin基因和c-erbB-2基因的表达与预后的关系。方法:用免疫组化S-P法检测80例乳腺癌组织中survivin、c-erbB-2的表达,分析其与腋淋巴结转移和5年无病生存率之间的关系。结果:survivin基因在乳腺癌中阳性表达率为68.75%(55/80)、c-erbB-2基因阳性表达率为36.25%(29/80),均与腋淋巴结转移正相关,与5年生存率负相关(P<0.05);survivin和c-erbB-2表达与肿瘤病理类型、发病年龄、临床分期无明显相关性(P>0.05);survivin和c-erbB-2基因表达相互呈正相关(P<0.05)。结论:凋亡抑制基因survivin和原癌基因c-erbB-2可能在乳腺癌的发生、发展过程中起重要作用,联合检测能更好地判断乳腺癌的预后。     

乳腺癌耐药蛋白在乳腺癌组织中的表达及与预后关系

目的研究乳腺癌耐药蛋白（Breast cancer resistance protein,BCRP）在乳腺癌组织中的表达,评估其在乳腺癌预后中的作用。方法采用免疫组织化学方法（Immunohistochemistry,IHC）检测47例手术切除的乳腺癌组织中BCRP的表达,并分析其与临床、病理特征的关系及对预后的影响。结果（1）BCRP在乳腺癌组织中的阳性表达率为55．3％（26／47例）,其中高表达者13例（27．7％）;（2）激素受体阳性者BCRP表达水平明显高于激素受体阴性者（P〈0．05）,BCRP表达与月经状况、肿瘤大小、腋淋巴结转移和组织分级均无关（P〉0．05）;（3）Kaplan—Meier生存分析结果表明BCRP和无病生存期相关（P〈0．05）,但和总生存期无关（P〉0．05）;（4）Cox单因素分析显示肿瘤大小和BCRP表达与无病生存期明显相关（P〈0．05）,而肿瘤大小和总生存期也明显相关（P〈0．05）;在多因素分析中BCRP表达仅和无病生存期明显相关,此外腋淋巴结转移与无病生存期和总生存期均明显相关（P〈0．05）。结论BCRP在乳腺癌组织中具有较高的表达水平,但与乳腺癌患者预后无关。     

The prognostic significance of ploidy analysis in operable breast cancer

The nuclear DNA content of 98 operable breast cancers was determined by flow cytometric analysis using paraffin-embedded tissue. All patients were on follow-up and failure of treatment or recurrences were identified. DNA ploidy data in the form of ploidy status and DNA index (DI) has been correlated with various clinical and histopathologic factors. The only significant correlation using univariate analysis exists between the histologic grade and DI (P less than 0.025), recurrence of the disease and ploidy status (P less than 0.005), and recurrence of the disease and DI (P less than 0.005). The absence of correlation of ploidy status with other tumor derived factors indicates the independent nature of ploidy as a prognostic factor. Multivariate analysis showed that in the whole-group ploidy (P less than 0.01), tumor margin (P less than 0.01), and menopausal status (P less than 0.01) were significant factors in the order mentioned. DI with a cut of at 1.29 is not found to be a significant factor in the multivariate analysis. The maximum prognostic value of ploidy status was observed in the postmenopausal group (P less than 0.0005). In the node-negative group ploidy status (P less than 0.05) is the only independent significant factor predicting for early relapse. It is concluded that ploidy status is an independent prognostic factor predicting for recurrence of the disease. In the node-negative subgroup this could be used to identify the subset of patients who may benefit from adjuvant treatment.     

乳腺癌趋化因子受体CXCR4的表达及其意义

目的研究趋化性细胞因子受体CXCR4在乳腺癌中的表达,探讨其与淋巴结转移、远处转移及预后的关系。方法84例正常乳腺组织及84例乳腺癌组织、43例区域淋巴结转移癌组织标本（依据组织类型及临床病理特性分组）,取自福建医科大学附属第二医院2000年1月至2002年12月手术切除的病理存档蜡块,应用免疫组化方法（二步法）分别检测3组标本CXCR4的表达情况。对计数资料采用χ^2检验,对生存率采用时序检验进行统计学分析。结果正常乳腺组织、乳腺癌组织、区域淋巴结转移癌组织CXCR4阳性率分别为11．9％、53．6％、74．4％;转移组织CXCR4阳性表达率明显高于原发肿瘤。乳腺癌组织CXCR4阳性表达率与淋巴结转移、HER-2表达、临床分期密切相关（P〈0．05）,而与患者年龄、肿瘤直径、ER表达、PR表达、组织学类型及肿瘤分化程度无关（P〉0．05）。发生远处转移组CXCR4表达水平（74．1％）高于未发生远处转移组（43．9％,P〈O．01）。CXCR4阳性表达组5年生存率66．7％（30／45）明显低于阴性表达组87．2％（84／89,P〈0．05）。结论CXCR4阳性表达与乳腺癌的淋巴结转移、远处转移有关,有助于预后判断。     

Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance

Breast cancer has been shown to live in the tumor microenvironment,which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells.Diverse components of the breast cancer microenvironment,such as suppressive immune cells,re-programmed fibroblast cells,altered extracellular matrix (ECM) and certain soluble factors,synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis.Among these components,stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways,whereas the ECM features biochemical and biomechanical changes.However,triple-negative breast cancer (TNBC),the most aggressive subtype of this disease that lacks effective therapies available for other subtypes,is considered to feature a unique microenvironment distinct from that of other subtypes,especially compared to Luminal A subtype.Because these changes are now considered to significantly impact breast cancer development and progression,these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC.In this review,we focus on the composition of the TNBC microenvironment,concomitant distinct biological alteration,specific interplay between various cell types and TNBC cells,and the prognostic implications of these findings.     

上皮钙黏蛋白在三阴性乳腺癌中的表达及其预后意义

目的探讨三阴性乳腺癌(TNBC)中上皮钙黏蛋白(E-cad)的表达情况及其对预后的影响。方法收集山西省肿瘤医院2009年4月至2012年4月收治的242例女性TNBC患者资料,用免疫组织化学法检测E-cad表达情况,应用Kaplan-Meier法和Cox比例风险回归模型分析E-cad表达对TNBC患者预后的影响。结果TNBC患者E-cad低表达率为59.5%(144/242),其表达与肿瘤临床TNM分期和淋巴结转移有关(均P<0.05)。242例患者中位总生存时间为70.7个月(7.2~95.9个月),50例(20.7%)患者死亡。3、5年的无病生存率分别为81.5%、78.1%,总生存率分别为86.5%、81.1%。E-cad低表达患者的无病生存及总生存率均低于高表达患者,差异均有统计学意义(均P<0.01)。Cox回归分析显示,E-cad是影响TNBC患者无病生存及总生存的独立预后因素(HR=0.144,95%CI 0.057~0.365,P<0.01;HR=0.196,95%CI 0.073~0.710,P<0.01)。结论E-cad低表达和TNBC的转移及预后差有关,其可作为TNBC患者一个重要的独立预后因子。     

Immunohistochemical demonstration of c-erb B-2 oncoprotein expression in female breast cancer and its prognostic significance.

The expression of c-erb B-2 oncoprotein was studied immunohistochemically in paraffin embedded biopsy specimens of 91 female breast carcinomas. The mean (+/- SD) age of the patients at diagnosis was 59.0 (+/- 13.2) years and they were prospectively followed-up for a mean of 12.4 years (range 11.5-13.3 years). The c-erb B-2 expression was analysed in relation to clinical stage, menopausal status, histological grade, tubular growth pattern, irregularity of nuclei, DNA ploidy and clinical outcome during the follow-up. Grade III tumours showed higher c-erb B-2 expression than low grade tumours and the c-erb B-2 expression than low grade tumours and the c-erb B-2 positivity was also related to the irregularity of the nuclei (p = 0.0815). Crude survival (p = 0.0635) and breast cancer survival (p = 0.072) could be predicted by c-erb B-2 expression, in that the c-erb B-2 negative tumours survived longer. The prediction of crude survival (p = 0.03), breast cancer survival (p = 0.04) and disease-free survival (p = 0.037) was more reliable in postmenopausal women. The results suggest that c-erb B-2 oncogene expression can be used as a prognostic parameter in predicting the biological behaviour of female breast cancer.     

乳腺癌组织PS2与雌激素和孕激素受体的关系及预后意义

目的 :探讨PS2在乳腺癌中的表达及其与雌激素受体 (ER)、孕激素受体 (PR)关系和预后意义。方法 :采用链亲和素(LSAB)法检测 110例乳腺癌中PS2的表达。结果 :PS2在乳腺癌组织中的阳性表达率为3 9 0 9% ( 4 3 / 110 ) ,其表达与患者年龄无关 ,P >0 0 5 ;与乳腺癌瘤体大小、腋淋巴结转移呈负相关 ,P <0 0 5。在ER阳性组和阴性组 ,PS2阳性率分别为 48 5 3 % ( 3 3 / 68)和2 3 81% ( 10 / 42 ) ,P =0 0 1;在PR阳性组和阴性组 ,PS2阳性率分别为 49 15 % ( 2 9/ 5 9)和2 7 45 % ( 14 / 5 1) ,P =0 0 2 ,PS2表达与ER、PR呈正相关关系。结论 :PS2可作为判断乳腺癌预后及预测术后抗雌激素治疗效果的重要指标     

HLA-G在乳腺癌中的表达及意义

目的 探讨乳腺癌患者组织中人类白细胞抗原G(Human leukocyte antigen,HLA-G)的表达及其在乳腺癌诊断和预后中的作用。方法 分离纯化HLA-G蛋白,筛选出分泌抗HLA-G单克隆抗体的杂交瘤细胞株,得到抗HLA-G单克隆抗体。用免疫组织化学方法检测235例乳腺癌患者组织中HLA-G的表达,分析HLA-G的表达与各项临床病理指标、宿主免疫反应及生存率之间的关系。结果 HLA-G在乳腺癌患者的表达率为66%(155/235),HLA-G表达与肿瘤大小、临床TNM分期以及淋巴结转移有关。HLA-G阴性病人的生存率明显高于HLA-G阳性病人。结论 乳腺癌组织中HLA-G有较高表达,HLA-G的表达与宿主免疫反应及乳腺癌的预后有关,HLA-G的表达可能是影响乳腺癌病人预后的独立因素。     

粘附分子E-cadherin在乳腺肿瘤中的异常表达及其意义

E—cadherin是介导上皮细胞间粘附的一种粘附分子,其功能异常与肿瘤的浸润和转移密切相关。乳腺肿瘤中,E—cadherin表达缺失或下降,在肿瘤的浸润转移过程中起着非常重要的作用。基因突变、基因启动子区甲基化或转录抑制等是E—cadherin表达异常的原因。     

乳腺癌组织中ASC基因的表达及临床意义

目的探讨乳腺癌和癌旁组织中ASC基因的表达及临床意义。方法选择2008年10月至2013年6月间100例乳腺癌组织标本和50例癌旁正常组织标本,所有患者术前均未经放疗和化疗,采用免疫组化Envi Sion方法检测癌组织与癌旁正常组织中ASC的表达情况。分析乳腺癌患者ASC基因的表达与年龄、雌激素(ER)、孕激素(PR)、人表皮生长因子2(HER-2)、p53基因、Ki-67、疾病分期和淋巴结转移的关系。结果乳腺癌和癌旁组织中ASC基因的阳性表达率分别为52.0%(52/100)和84.0%(42/50),组间阳性表达差异有统计学意义(P<0.05)。乳腺癌组织中ASC基因的表达与患者年龄、淋巴结转移、术后分期以和病理类型无明显相关性(P>0.05),与ER、PR、HER-2、p53和Ki-67表达也无明显相关性(P>0.05)。结论 ASC基因在乳腺癌中表达减低,提示ASC在乳腺癌的凋亡、发生、发展过程中起重要作用,可能成为乳腺癌早期诊断的指标之一。     

Comparative survival analysis of breast cancer microarray studies identifies important prognostic genetic pathways

Background  

An estimated 12% of females in the United States will develop breast cancer in their lifetime. Although, there are advances in treatment options including surgery and chemotherapy, breast cancer is still the second most lethal cancer in women. Thus, there is a clear need for better methods to predict prognosis for each breast cancer patient. With the advent of large genetic databases and the reduction in cost for the experiments, researchers are faced with choosing from a large pool of potential prognostic markers from numerous breast cancer gene expression profile studies.