Relationships between histology, monoclonal antibody reactivity, and prognosis in breast cancer

Infiltrating ductal carcinoma of the breast is histologically heterogeneous and may be subdivided into three main types (A, B, and C) which correlate with the likelihood of long-term survival. Examples of each type were tested against three monoclonal antibodies (H59, H71, and H72) prepared against the breast cancer cell line ZR-75-1. The reaction patterns of type B tumors were significantly different from those of types A and C with antibodies H59 and H71, but not with H72. Thus, the reactivity to these monoclonal antibodies, and presumably the antigen composition of the tumor cells, correlates with the histologic appearances and probability of long-term survival.     

乳腺癌分子亚型中CAIX的表达及临床意义

目的：探讨乳腺癌各分子亚型中碳酸酐酶IX(carbonic anhydrase IX,CAIX)的表达及临床意义。方法：采用免疫组织化学检测CAIX在4种不同乳腺癌分子亚型中的表达水平并分析其与临床病理参数的关系。结果：CAIX在管腔A型、管腔B型、HER-2过表达型和基底样型乳腺癌中的阳性表达率分别为6.65%(28/421)、12.50%(7/56)、60.61%(40/66)和32.31%(84/260)。ER阴性的HER-2过表达型及基底样型乳腺癌组织中,CAIX的阳性表达明显高于ER阳性的管腔A型和管腔B型(P<0.001),并且HER-2过表达型乳腺癌组织CAIX的阳性表达率明显高于基底样型相比,差异有统计学意义。CAIX与乳腺癌的组织学分级、淋巴结转移、临床分期及高增殖指数相关(P<0.05),而与患者年龄、是否绝经及肿瘤大小无关。结论：CAIX在不同乳腺癌分子亚型中的表达具有明显差异,可能与ER阴性乳腺癌关系更密切,并在乳腺癌的侵袭、转移中发挥重要作用,可能成为乳腺癌浸润、进展及预后评估的指标。     

Relationships between vascularization and proliferation in invasive breast cancer.

Studies on relationships between angiogenesis and tumour cell proliferation have provided conflicting results. This study has therefore investigated the relationships between the number and location of fully automatically identified CD31-positive microvessels and interactively segmented mitoses and necrotic compartments by image processing. These features were studied in ten invasive breast cancers, in the 'hot spots' and in whole tumour sections. Microvessel and mitosis hot spots were topographically close or overlapping and were always located at the periphery of the tumour. The numbers of mitoses and microvessels per mm(2) in the hot spot were strongly correlated with the respective numbers in the whole tumour section, as well as mutually. The ratio of mitoses in the hot spot to the whole tumour section was significantly higher than the corresponding microvessel ratio. Mitoses were preferentially located at a distance of 50-150 microm from microvessels. No significant difference was found between the average distance between mitoses and microvessels in the whole tumour sections and in the hot spot (79 vs. 72 microm), although considerable inter-tumour differences were found (hot spot 43-101 microm, tumour 47-111 microm). The presence of necrotic areas correlated with the number of mitoses per mm(2) and necrosis was in general observed at a distance of more than 150 microm from the microvessels, suggesting that necrotic areas have outgrown their vascular system. These results indicate the usefulness of image processing of whole tumour sections for the identification of proliferation and vascularization hot spots, which are strong prognostic factors in breast cancer. The results also support a close relationship between tumour necrosis and microvessels.     

Relationships between emotional control, adjustment to cancer and depression and anxiety in breast cancer patients

The possible relationship between psychological responses among breast cancer patients and disease outcome continues to be an area of controversy and debate. Two parallel findings are reported separately in the literature: first, that emotional control is more common among women with breast cancer than in women with benign breast disease or in healthy controls and second, that a helpless attitude towards the disease is related to a poor prognosis. These previously unrelated psychological responses are examined here in a group of women (N = 359) with early stage breast cancer, who were seen one to three months after diagnosis. The relationships between emotional control, adjustment to cancer and psychological morbidity were examined. Prevalence levels of 16 and 6% were observed for anxiety and depression respectively, which are lower than reported more generally in the literature. The results indicated a highly significant association between scores for the tendency to control emotional reactions and a fatalistic attitude toward cancer. A significant association was observed between anger control and a helpless attitude. Psychological morbidity was also linked to type of adjustment to cancer. The data are interpreted in terms of a process model of psychological responses which suggests that emotional control (an important component of the Type C behaviour pattern) fatalism, helplessness and psychological morbidity are linked.     

乳腺癌中环氧化酶-2的表达及其与VEGF、MVD、MMP-9、 TIMP-1的关系

目的研究乳腺癌组织中环氧化酶-2（COX-2）的表达及其与VEGF、MVD、MMP-9和TIMP-1的相互关系,探讨其在乳腺癌发生和浸润中的生物学意义。方法应用S-P法检测65例浸润性乳腺癌组织中COX-2、VEGF、MMP-9、TIMP-1及血管内皮标记物CD34的表达情况,并观察7例导管原位癌（DCIS）、45例癌旁乳腺组织中COX-2的表达。结果65例浸润性乳腺癌、7例DCIS均表达COX-2,其中浸润性乳腺癌中COX-2高表达率为66．2％（43／65）,而45例癌旁组织中21例有COX-2弱表达,两者之间差异有显著性（P〈0．01）。COX-2与乳腺癌患者的年龄、肿瘤大小、组织学分级、TNM分期、腋窝淋巴结转移均无相关性,但COX-2在浸润性乳腺癌中的表达与VEGF、MMP-9、TIIMP-1及MVD均呈正相关（P〈0．05）。结论COX-2可能与乳腺癌组织中微血管形成和细胞外基质代谢有关。     

基底细胞样型乳腺癌中CAIX的表达及临床意义

目的 探讨碳酸酐酶IX(carbonic anhydrase IX,CAIX)在基底细胞样型乳腺癌(basal-like breast carcinomas,BLBCs)中的表达,分析其与乳腺癌患者相关临床病理指标的关系.方法 应用免疫组化SP法检测CAIX在45例BLBCs、25例非基底细胞样型乳腺癌(non- basal-like breast carcinomas,non-BLBCs)和10例正常乳腺组织中的表达.结果 免疫组化检测结果显示,CAIX在BLBCs组织中的阳性表达率明显高于non-BLBCs和正常乳腺组织(P<0.05);BLBCs组织中CAIX的表达与肿瘤直径(P=0.001)、pTNM分期(P=0.014)及淋巴结转移(P=0.006)均呈正相关(P<0.05).结论 CAIX在BLBCs中高表达,提示其可能参与该型乳腺癌病程进展的重要分子;CAIX的表达与多项临床病理指标、尤其是淋巴结转移密切相关,提示其可作为预测BLBCs淋巴结转移及预后的指标.     

DAPK1基因启动子甲基化与乳腺癌临床病理特征的关系

目的：研究乳腺癌组织中死亡相关蛋白激酶（death-associated protein kinase 1,DAPK1）启动子甲基化状态及其与临床病理特征之间的关系,并探讨该甲基化状态与DAPK1 mRNA表达的相关性。方法：应用甲基化特异性PCR法检测人乳腺癌组织和相应癌旁正常乳腺组织中DAPK1启动子甲基化状态,分析其与患者临床病理特征的关系,并结合半定量RT-PCR法的检测结果加以分析。结果：43例乳腺癌标本中DAPK1启动子甲基化阳性率为44.1%（20/43）,DAPK1启动子甲基化状态与年龄、肿瘤大小、组织学分级、TNM分期、ER状态、PR状态、Her2状态无关（P〉0.05）,而与有无淋巴结转移、P53是否阳性有关（P〈0.05）。DAPK1启动子甲基化标本中的DAPK1mRNA表达水平低于未甲基化标本,两者差异具有统计学意义（P〈0.05）。结论：乳腺癌中DAPK1基因启动子区高甲基化与其mRNA失表达有关,在乳腺癌发生、发展中可能起重要作用,有可能作为乳腺癌诊断和预后分析的检测指标之一。     

乳腺癌的复发、转移与c-erbB-2、BCSG1等多指标相关性研究

 目的：探讨人表皮生长因子受体（c-erbB-2）、乳腺癌特异基因(BCSG1)等多指标在乳腺癌中的表达及其对复发、转移的影响以及其间的相关性。方法：采用免疫组化SP法检测随机抽取的随访5年临床病理资料完整的58例浸润性乳腺癌组织中的c-erbB-2、BCSG1以及雌激素受体（ER）、孕激素受体（PR）、微血管计数（MVD）、血管内皮生长因子（VEGF）、淋巴管内皮生长因子（VEGF-C）、淋巴管内皮生长因子受体（FLT-4）、淋巴管计数（LVD）蛋白的表达情况，结合临床、病理形态学资料分析多项指标对复发、转移的影响。结果：c-erbB-2、BCSG1、VEGF-C、LVD蛋白在乳腺癌组织中的阳性表达率分别为25.9%、62.1%、36.2%、32.8%；4指标表达在伴淋巴结转移组明显高于无转移组（P<0.05）；在复发、转移组其表达率同样显著高于无复发、转移组（P<0.05），且MVD在复发、转移组也增高（P<0.05）。结论：c-erbB-2、BCSG1、VEGF-C、LVD蛋白与患者的复发、转移密切相关，乳腺癌c-erbB-2、BCSG1蛋白在乳腺癌中的表达呈正相关，其中，BCSG1蛋白表达的灵敏性高，可尝试作为预测乳腺癌预后的指标。     

ALEX1在乳腺癌中的表达及其临床意义

目的:检测乳腺癌组织中ALEX1的表达水平,明确ALEX1与其临床病理特征是否具有相关性。方法:应用real-time PCR、免疫组化方法检测乳腺癌组织中ALEX1含量。结果:乳腺癌组织ALEX1蛋白的表达水平低于癌旁组织(P0.01);ALEX1的表达与乳腺癌病理分级、临床分期和分子分型有关(P0.05),而与病人年龄、肿瘤大小和肿瘤类型无关。此外,real-time PCR结果表明,乳腺癌组织中ALEX1的mRNA表达明显低于对应的癌旁组织(P0.01)。结论:ALEX1在乳腺癌组织中的表达明显低于相应的癌旁组织,乳腺癌的病理分级、临床分期越高,ALEX1的表达水平越低。     

乳腺癌中RIN1的表达及临床意义

目的 研究RIN1在乳腺癌中的表达,分析它与乳腺癌预后的关系.方法 用免疫组化SP法检测85例乳腺癌和20例乳腺良性病变组织中RIN1的表达,并对85例乳腺癌病例进行随访;用real-time PCR和Western blot 法检测RIN1在20例乳腺癌和癌旁组织中的表达.Kaplan-Meier分析生存结果.结果 85例乳腺癌标本中RIN1有不同程度表达,其中44例高表达,乳腺癌中RIN1的表达明显高于非癌组织(P＜0.05);RIN1高表达与肿瘤最大直径、组织学分级、肿瘤家族史成正相关(P＜0.05);RIN1高表达患者的平均生存时间低于RIN1低表达患者(P＜0.05);RIN1高表达影响肿瘤无病生存率(P＜0.05).20例标本中RIN1的mRNA及蛋白在乳腺癌的表达明显高于癌旁组织(P＜0.05).结论 RIN1影响乳腺癌的发生发展,其高表达RIN1可能成为判断乳腺癌预后的一个标志物.     

人肺癌和乳腺癌组织IL-15的表达与临床病理因素相关分析

目的检测人体肺癌和乳腺癌组织中IL-15和IL-15Rα的表达及NK细胞和CD8^＋细胞的浸润,以探求IL-15在人体肺癌和乳腺癌发生发展中的作用。方法用免疫组化方法,检测29例肺癌和51例乳腺癌肿瘤组织标本中IL-15和IL-15Rα的表达及NK细胞和CD8^＋细胞的浸润,分析IL-15、IL-15Rα、NK细胞、CD8^＋细胞之间相关关系及与临床病理因素之间的关系。结果肺癌和乳腺癌肿瘤组织中IL-15表达的阳性染色密度值（PSD）随临床分期增加而减少,肿瘤直径〈3cm组大于肿瘤直径≥3cm组,无淋巴结转移组大于有淋巴结转移组。两种肿瘤组织中IL-15的表达和IL-15Rα的表达没有相关性,与NK细胞、CD8^＋细胞的浸润成正相关。IL-15Rα的表达与这两种肿瘤病人的临床分期、肿瘤大小、淋巴结转移无关。结论IL-15高表达者,多处于肿瘤分期早期,瘤体体积较小,少伴有淋巴结转移;IL-15低表达者,多处于肿瘤分期晚期,瘤体体积较大,多伴有淋巴结转移。推测IL-15在这两种肿瘤发生发展中可能起抑制作用。     

非小细胞肺癌组织中MMP-9、TIMP-1表达及意义

目的 探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中基质金属蛋白酶9(MMP-9)、组织金属蛋白酶抑制剂-1(TIMP-1)的表达及其生物学行为的关系.方法 应用免疫组织化学SP法检测76例NSCLC和癌旁正常组织中MMP-9、TIMP-1的表达,并分析其表达与肺癌组织类型、肿瘤大小、TNM分期、分化程度、淋巴结转移的相关性.结果 MMP-9、TIMP-1在肺癌组织中的阳性表达率明显高于癌旁正常组织(P<0.05).NSCLC中MMP-9、TIMP-1表达与肿瘤的分化程度、临床分期、淋巴结转移有相关性(P<0.05),与肿瘤病理分型无关(P>0.05).结论 检测NSCLC中组织的MMP-9、TIMP-1的表达对判断肿瘤的恶性程度和预后评估有一定的意义.     

STAT3 and STAT5b polymorphism contributes to breast cancer risk and clinical outcomes

We conducted a case-control study in a Chinese population, and investigated the role of STAT3 rs4796793 and STAT5b rs6503691 polymorphisms in the risk and clinical outcome of breast cancer. STAT5b rs6503691 polymorphisms and STAT3 rs4796793 polymorphisms were genotyped by TaqMan SNP Genotyping Assays on the ABI 7500 fast real-time PCR platform. Unconditional logistic regression analyses showed that subjects carrying the GG genotype of STAT3 rs4796793 had a significantly increased risk of breast cancer, with an adjusted OR (95% CI) of 0.35 (0.12-0.95). In the Cox proportional hazards model, we observed that individuals carrying CG+GG genotype of STAT3 rs4796793 was associated with reduced risk of death from breast cancer when compared with CC genotype (HR = 0.43, 95% CI = 0.20-0.93). Our study found that STAT3 rs4796793 polymorphism plays an important role in influence the development and overall survival of breast cancer patients.     

乳腺癌和乳腺导管内增生性病变Notch1基因甲基化的检测及临床意义

Objective To explore the relevance between the promoter methylation status of Notch1gene and the invasive ductal carcinoma and ductal hyperplastic lesions of the breast.Methods Methylation status of Notch1 gene in human breast invasive ductal carcinoma(IDC,n=89),ductal carcinoma in situ (DOS,n=20),atypical ductal hyperplasia(ADH,,n=11)and usual ductal hyperplasia(UDH,n=20)were quantitatively evaluated by MALDI-TOF MS.The expression of Notch1 protein was detected by immunohistochemical stain(SP method).Results Positive expression rates of Notch1 protein in IDC and DCIS were 91.0%(81/89)and 75.0%(15/20),respectively,which were significandy higller than those 0f ADH(4/11)and UDH(30.0%.6/20;P＜0.05).Notch1 protein expression was correlated significantly with lymph node metastasis,pathological grades and TNM stages of IDC.The mean methylation levels of Notch1 gene at CpG_3,CpC 4.5 and CpG_8 significantly decreased in IDC group compared with those of DCIS.ADH and UDH groups(P＜0.0083).In breast carcinomas, the mean methylation rates of Notch1 gene at CpG-4.5,CpG-10.11,and CpG_14.15.16 loci in cases with axillary node metastasis were significantly lower than those without axillary node metastasis(P＜0.05):and the methylation rates at CpG_14.15.16 and CpG_18 lociin stage Ⅰ were lower than that in stage Ⅱ,further lower than that in stage Ⅲ(P＜0.05);and that in CpG_1.2,CpG_12.13 loci in grade Ⅰ(highly-differentiated group)were higher than that in grade Ⅱ(moderate-differentiated group)and grade Ⅲ(peody-differentiated group) (P＜0.05);and the methylation rates at CpG_3,CpG_8 and CpG_14.15.16 loci in ER+ PR+ HER2-group were lower than that in ER-PR-HER2+ group(P＜0.05).Conclusions There is an overall hypomethylation of Notch1 gene in breast invasive ductal carcinomas with corresponding over-expression of Notehl protein.This inverse correlation show that the alteration of protein expression result from hypomethylation oncogene Notch1,and this change may have important significance in breast tumorigenesis and the development.Specific hypomethylation at CpG_3,CpG_4.5 and CpG_8 loci of Notehl gene may play a role in the pathogenesis of breast carcinoma,suggesting the progression and/or malignant transformation from benign glandular lesions of the breast.     

乳腺癌和乳腺导管内增生性病变Notch1基因甲基化的检测及临床意义

目的 探讨Notch1基因甲基化与乳腺浸润性导管癌(IDC)及乳腺导管内增生性病变的相关性.方法 用基质辅助激光解析电离时间飞行质谱仪(MALDI-TOF MS)对89例乳腺IDC、20例导管原位癌(DCLS)、11例不典型导管增生(ADH)及20例普通型导管增生(UDH)组织进行Notch1基因甲基化的定量检测.采用...     

Relationships between oestrogen receptor,epidermal growth factor receptor, ER-D5, and P24 oestrogen regulated protein in human breast cancer

Proteins regulated by or related to the oestrogen receptor (ER) may prove to be more reliable indicators of prognosis and hormone sensitivity then expression of the receptor itself. It has been shown recently that expression of epidermal growth factor receptor (EGFR) is associated with a poor prognosis in breast cancer. In a series of 60 breast cancers, we have studied relationships between ER, ER-D5 oestrogen receptor related protein, P24 oestrogen regulated protein, and EGFR using an immunohistochemical technique employing monoclonal antibodies in each case. In addition, radioligand binding assays for ER and EGFR were carried out and tumour histological grade was determined. Seventy-one per cent and forty-three per cent of tumours stained for ER-D5 and P24, respectively, but there was no relationship between staining for these and ER or EGFR status. There was a significant correlation between staining for ER and EGFR, and the respective biochemical assays. Relating ER to EGFR, very few ER-positive cases expressed EGFR, but this relationship fell short of significance. The prognostic significance of expression of the epitopes recognized by the ERD5 and P24 antibodies must await assessment of clinical outcome.     

Diagnostic power of VEGF,MMP-9 and TIMP-1 in patients with breast cancer. A multivariate statistical analysis with ROC curve

PurposeVascular endothelial growth factor is an important factor in promoting angiogenesis in malignant processes, matrix metalloproteinase-9 in the degradation of extracellular matrix, which enhances metastasis, and tissue inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to investigate the diagnostic power of these parameters in comparison to CA15-3 in breast cancer patients and in relation to the control group.Materials/methodsThe study included 120 breast cancer patients, 60 patients with benign breast tumors and 60 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle immuno assay.ResultsTissue inhibitor of metalloproteinase-1 showed the highest value of sensitivity in breast cancer group (86.25%) and, more importantly, highest value in breast cancer stage I (85%). Vascular endothelial growth factor also showed high sensitivity (stage I and II–75%, III–85%, IV–70% and 76.25% in total breast cancer group) and the highest specificity (85%) from all tested parameters. It was also the only parameter which had statistically significant area under curve in all stages. In the total breast cancer group all tested parameters showed statistically significant area under curve, but the maximum range was obtained for combination: ‘vascular endothelial growth factor + CA15-3′. Vascular endothelial growth factor seems to be the best candidate for diagnosing breast cancer stage I and for differentiating between breast cancer and non-carcinoma cases.ConclusionsThe combined analysis of tested parameters and CA15-3 resulted in an increase in sensitivity and area under curve values, which provides hope for developing new panel of biomarkers that may be used in diagnosing breast cancer in the future.