乳腺增生症增殖细胞核抗原表达的定量研究

目的：探讨增殖细胞核抗原(PCNA)在乳腺增生症组织中表达的意义及其与乳腺癌的关系。方法：应用免疫组化方法结合图象分析技术对根据Page标准分为3级的44例乳腺增生症(FCD)及28例乳腺浸润性导管癌(IDC)患者及5例正常乳腺组织(NMB)中的PCNA表达进行定量测定。结果：PCNA含量按NMB、乳腺增生症Ⅰ级(FCD1)、FCD2、FCD3及IDC的顺序递增，除FCD1与NMB组外，其余相邻组间差异均有统计学意义。结论：1)PCNA含量增加是乳腺上皮不典型增生的一个重要特征；2)PCNA的定量测定可以较为客观地评价乳腺上皮的增生程度及良、恶性。     

乳腺增生症增殖细胞核抗原表达的定量研究

目的 :探讨增殖细胞核抗原(PCNA)在乳腺增生症组织中表达的意义及其与乳腺癌的关系。方法 :应用免疫组化方法结合图象分析技术对根据Page标准分为 3级的 44例乳腺增生症(FCD)及 2 8例乳腺浸润性导管癌 (IDC)患者及 5例正常乳腺组织 (NMB)中的PCNA表达进行定量测定。结果 :PCNA含量按NMB、乳腺增生症Ⅰ级 (FCD1)、FCD2 、FCD3 及IDC的顺序递增 ,除FCD1与NMB组外 ,其余相邻组间差异均有统计学意义。结论 :1)PCNA含量增加是乳腺上皮不典型增生的一个重要特征 ;2 )PCNA的定量测定可以较为客观地评价乳腺上皮的增生程度及良、恶性。     

膜联蛋白A1的表达差异同乳腺癌发生发展相关性的初步研究

目的检测膜联蛋白A1(Annexin A1)在正常乳腺组织、乳腺良性增生、癌前病变及乳腺癌中的表达,以探讨其表达差异同乳腺癌发生发展的相关性。方法应用免疫组织化学SABC方法和蛋白印迹检测乳腺正常组织、良性病变(纤维腺瘤)、癌前病变(乳腺囊性增生症)、非浸润性导管癌、浸润性导管癌中Annexin A1的表达情况。结果Annexin A1的染色评分在20例癌旁正常乳腺组织为1.5328±0.45603;在20例良性病变为1.3250±0.56928;在20例癌前病变为0.9125±0.40324;在20例非浸润性导管癌为0.1550±0.20125;在40例浸润性导管癌为0.1038±0.12004。正常乳腺组织、乳腺囊性增生症、乳腺癌3组间差异显著(P<0.01)。乳腺囊性增生症、良性增生、乳腺癌3组间差异显著(P<0.01)。良性增生与正常组织之间,非浸润导管癌与浸润性导管癌之间无显著差异(P>0.05)。乳腺癌中Annexin A1表达水平与乳腺肿瘤大小及临床分期有关(P<0.05),与患者绝经与否、乳腺癌组织学分级、淋巴结转移与否等无显著差异(P>0.05)。蛋白印迹结果与上述结果一致。结论Annexin A1表达水平在乳腺癌及其癌前病变组织中有不同程度的下调,下调程度与乳腺癌发生的危险性及恶性度密切相关,提示Annexin A1可以作为乳腺癌发生趋势预测、早期诊断、评价预后具有重要应用价值的指标。     

乳腺浸润性导管癌中Clusterin蛋白表达及其与临床病理特征的关系

[目的]探讨细胞凋亡抑制因子Clusterin在乳腺浸润性导管癌组织中的表达及其与临床病理因素的关系。[方法]应用免疫组化SP法检测70例乳腺浸润性导管癌、20例乳腺增生和10例乳腺癌旁组织标本中Clusterin的表达情况。[结果]Clusterin在乳腺癌旁正常组织、乳腺增生及乳腺浸润性导管癌组织中的阳性表达率分别为0、20.0%及71.4%,乳腺浸润性导管癌组织中的Clusterin表达水平明显高于乳腺增生及乳腺癌旁正常组织(P<0.05)。Clusterin蛋白在乳腺浸润性导管癌中的表达与临床分期、组织学分级及淋巴结转移情况有关(P<0.05),而与患者年龄、肿瘤大小无关(P>0.05)。在乳腺浸润性导管癌组织中Clusterin与ER、PR的表达呈负相关(P<0.05)。[结论]Clusterin可能在乳腺癌的发生发展中发挥重要促进作用,可望成为乳腺浸润性导管癌诊断中的标志物及新的治疗靶点。     

p57KIP2、cyclin E在乳腺浸润性导管癌中的表达及意义

目的检测p57KIP2、cyclin E蛋白在乳腺浸润性导管癌(IDC)中的表达,探讨它们在乳腺癌发生、发展中的作用.方法采用免疫组织化学SP法检测64例IDC、15例乳腺导管内癌(DCIS)、15例癌旁正常乳腺组织中p57KIP2、cyclin E蛋白的表达情况.结果p57KIP2、cyclin E蛋白在IDC与DCIS、IDC与癌旁正常组织中阳性表达之间,cyclin E蛋白在DCIS与癌旁正常组织中阳性表达之间差异均有显著性(P≤0.05,P＜0.01).在IDC中,p57KIP2、cyclin E蛋白阳性表达均与腋窝淋巴结转移相关(P＜0.01,P≤0.05),与患者年龄无关(P＞0.05);cyclin E蛋白阳性表达与肿块大小有关(P＜0.01);p57KIP2与cyclin E之间阳性表达呈负相关(P＜0.01).结论p57KIP2蛋白低表达、cyclin E蛋白高表达可能是乳腺组织恶性转变以及乳腺癌发生淋巴结转移的重要生物学标志,cyclin E蛋白的异常表达是乳腺癌发生的早期事件.联合检测p57KIP2、cyclin E对预测乳腺癌淋巴结转移有临床意义.     

老年女性乳腺浸润性导管癌组织中分化抑制因子1的表达及意义

目的探讨老年女性乳腺浸润性导管癌组织中分化抑制因子1(Id~(-1))的表达及意义。方法选择45例老年女性乳腺浸润性导管癌标本(研究组)和30例乳腺良性病变标本(对照组),应用免疫组织化学方法检测Id~(-1)的表达,并进行半定量评分,分析Id~(-1)表达与老年女性乳腺浸润性导管癌淋巴结转移、组织学分级及雌激素受体(ER)、孕激素受体(PR)之间的关系。结果研究组患者中Id~(-1)阳性表达率为80.0%,显著高于对照组,差异有统计学意义(P<0.05);有淋巴结转移的乳腺癌组织中Id~(-1)阳性表达率显著高于无淋巴结转移者,组织学分级Ⅲ级患者的Id~(-1)阳性表达率显著高于Ⅰ~Ⅱ级者,ER、PR阳性患者的Id~(-1)阳性表达率明显低于阴性者,差异有统计学意义(P<0.05)。结论 Id~(-1)过表达可能与老年乳腺浸润性导管癌的发生、发展及恶性生物学行为密切相关,检测Id~(-1)表达对老年乳腺浸润性导管癌的诊治及预后判断有重要价值。     

乳腺癌组织中端粒酶活性的定量检测及其与临床病理的关系

背景与目的:端粒酶是一种在细胞永生化及癌症发生过程中起重要作用的核蛋白酶。最近关于乳腺癌中端粒酶活性与预后因素间的关系,因研究方法的差异而呈现出不一致的报道。本研究旨在建立一种可行的银染端粒酶定量检测法,以探讨乳腺癌中端粒酶活性与临床病理学预后因素间的关系。方法:运用银染端粒重复序列扩增法(SS-TRAP)检测了52例新鲜乳腺癌及其癌旁组织,32例乳腺良性病变和14例正常乳腺组织中端粒酶的活性表达,对结果予以定量并结合临床资料进行分析。结果:乳腺癌、癌旁组织、良性病变及正常乳腺组织中端粒酶阳性率分别为90.38%(47/52)、28.85%(15/52)、31.25%(10/32)、0(0/14)。端粒酶分别为36.91±15.35、8.27±4.37、14.10±5.28、0(TPG单位),单因素方差分析结果显示,乳腺癌组端粒酶活性水平明显高于其他3组(P值均<0.01)。Logistic回归分析结果表明,乳腺癌中端粒酶的表达与病理类型、分化程度明显相关(P=0.003及0.004),即随着肿瘤的进展,端粒酶活性亦增加。其中,浸润性非特殊癌端粒酶活性水平明显高于浸润性特殊癌(P<0.05);中、低分化癌端粒酶活性均高于高分化癌(P<0.05),中、低分化癌间无显著性差异(P>0.05)。端粒酶活性表达在患者病程、年龄、绝经状况间均无显著性差异(P>0.05)。结论:与经典TRAP     

端粒酶活性在乳腺癌中表达的研究

:[目的]探讨端粒酶在乳腺癌中的活性表达情况。[方法]利用非放射性的PCR ELISA反应试剂盒检测51例乳腺癌及其中20例癌旁组织和9例正常乳腺组织的端粒酶活性。[结果]51例乳腺癌、20例癌旁组织和9例正常乳腺组织的端粒酶活性阳性率分别为82 4 %(42/51)、5 %(1/20)和0(0/9) ;乳腺癌中不同组织分类之间及不同临床分期之间的端粒酶活性阳性率均无显著差异(P>0 05)。[结论]端粒酶在绝大多数乳腺癌中表达 ,其活性与乳腺癌的组织分类、临床分期和肿瘤大小无相关性。     

乳腺浸润性导管癌中Paxillin和Caspase-3蛋白的表达及临床意义

  目的  探讨桩蛋白（Paxillin）和天冬氨酸特异性半胱氨酸蛋白酶-3（Caspase-3）在乳腺浸润性导管癌（IDC）中的表达及其与乳腺浸润性导管癌（IDC）患者临床病理因素的关系。   方法  采用免疫组化检测术中切除的原发性乳腺浸润性导管癌（IDC）和距癌灶约5 cm处正常乳腺组织中Paxillin和Caspase-3的表达,统计学分析两者间及其与乳腺浸润性导管癌（IDC）病理特征的关系。   结果  Paxillin在IDC组的表达高于正常乳腺组织组,差异具有统计学意义（P < 0.05）;Caspase-3在IDC组的表达低于正常乳腺组织组,差异具有统计学意义（P < 0.05）。在IDC组中,Paxillin的表达与Her-2状态相关,2种蛋白的表达与乳腺IDC的淋巴结转移及组织学分级相关,2种蛋白在IDC中的表达呈负相关（r=-0.32,P=0.013）。   结论  Paxillin和Caspase-3的的异常表达在乳腺浸润性导管癌（IDC）的发生、发展中可能起着重要的作用,且与乳腺浸润性导管癌（IDC）的浸润转移密切相关。      

TRAF4蛋白在乳腺癌组织中的表达及意义

背景与目的:对肿瘤坏死因子受体相关因子4(tumor necrosis factor receptor-associated factor 4,TRAF4)在乳腺癌中表达的研究存在争议.本研究探讨TRAF4在正常乳腺组织、乳腺癌组织及不同侵袭能力乳腺癌细胞系中的表达情况.方法:应用免疫组化方法检测TRAF4在70例乳腺癌组织和14例正常乳腺组织中的表达.应用Western blot方法检测TRAF4在乳腺癌细胞系MDA-MA-231(高侵袭)和MCF-7(低侵袭)中的表达.结果:TRAF4在正常乳腺组织中呈浆、核阳性表达.其浆阳性率在正常乳腺组织(78.57%)、非浸润性导管癌(88.57%)和浸润性导管癌(91.43%)中逐渐增高,但差异无统计学意义(P＞0.05).而核阳性率在正常乳腺组织(64.28%)中显著高于非浸润性导管癌(28.57%,P＜0.01),在非浸润性导管癌中高于浸润性导管癌(5.7%,P＜0.05).TRAF4总蛋白在乳腺癌高侵袭细胞系中的表达量高于低侵袭细胞系,但差异无统计学意义(P＞0.05).结论:TRAF4在乳腺癌细胞核中表达明显降低,与乳腺癌侵袭性相关.     

Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma <Emphasis Type="Italic">in situ</Emphasis> (DCIS) is an early event in breast tumorigenesis

Focal adhesion kinase (FAK) is a protein tyrosine kinase that is overexpressed in a subset of invasive breast cancers. FAK transmits signals that mediate several functions including tumor cell proliferation, migration, adhesion and survival. We used immunohistochemical techniques to assess FAK expression in patients with fibrocystic disease (FCD), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC). Formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained from 119 patients (12 FCD, 38 ADH, 51 DCIS and 18 IDC). The anti-FAK 4.47 monoclonal antibody was used to detect FAK expression. FAK expression was scored as high (3 or 4 intensity and 90 positive cells) or low. The DCIS tissue sections demonstrated high FAK expression in 34/51 (66) of the sections. High FAK expression was demonstrated in 6/18 (33) of the IDC tissue sections and 8/38 (21)of the ADH tissue sections. None (0/12) of the FCD tissues sections stained high for FAK. The pattern of FAK expression in DCIS was significantly higher than ADH (p < 0.0001) and IDC (p =0.02). We conclude that FAK overexpression in preinvasive, DCIS tumors precedes tumor cell invasion or metastasis, suggesting that FAK may function as a survival signal and be an early event in breast tumorigenesis.     

Telomerase activity in ductal carcinoma in situ of the breast

Telomerase plays an important role in maintaining the stability of the chromosomes. Activity of telomerase has been detected in proliferating and immortalized cell lines and in a number of malignant tumors including invasive breast cancer. The aim of the study was to examine telomerase activity in ductal carcinoma in situ (DCIS), which is considered to be a precursor lesion of infiltrating breast carcinoma, using a PCR-based telomerase activity protocol (TRAP). We examined 35 samples obtained from histologically confirmed breast biopsies, including 13 normal breast tissues, 11 infiltrating ductal carcinoma (IDC), nine DCIS, and two DCIS with microinvasion. Telomerase activity was demonstrated in 8/9 samples of DCIS, both samples of DCIS with microinvasion, and all but one sample of IDC. Normal breast tissue had no demonstrable telomerase activity. Our results indicate that telomerase is activated frequently in early breast carcinogenesis, although its utilization as a biomarker in DCIS is questionable.     

Telomerase activity in human breast cancer and benign breast lesions: Diagnostic applications in clinical specimens,including fine needle aspirates

We analysed telomerase activity in normal, benign and malignant breast tissues and in fine needle aspirates by a PCR-based assay. The tissue samples we used in this assay consisted of 20 cryostat sections, 10 μm thick, from each breast biopsy. This method was used to obtain effective extraction from small samples and to confirm the histological identity of the specimen by microscopical examination of serial sections. Fifty-two of 71 breast carcinomas were positive for telomerase activity, and the intensity of this was strong in most cases, whereas all 6 samples of normal breast tissue and 17 of fibrocystic disease were negative and only 1 of 15 fibroadenomas was positive. Invasive ductal carcinomas were more frequently positive than invasive lobular carcinomas. There was no correlation of telomerase activity with tumour size or the occurrence of lymph node metastasis. Evaluation of our assay system showed that a signal of telomerase activity was detectable in extracts from single cryostat sections (> 1 mm²) of a cancer specimen and from as few as 4 cells of a human breast cancer cell line. On the basis of the above data, we applied this assay to fine needle aspirates of breast lesions. Ten of 15 aspirates which had been cytopathologically diagnosed as cancer were strongly positive, while 26 of 29 benign aspirates were totally negative and the remaining 3 showed only borderline activity. In 3 cases, the telomerase result could have helped establish a diagnosis when the cytological observations were inconclusive. Our results indicate that this sensitive assay could become a useful new modality for supplementing microscopic cytopathology in the detection of cancer cells in small tissue biopsies and fine needle aspirates. © 1996 Wiley-Liss, Inc.     

乳腺癌组织中端粒酶活性的研究

目的 :研究乳腺癌组织、癌旁组织、良性乳腺病变、正常乳腺组织中的端粒酶活性 ,探讨其作为乳腺癌肿瘤标志物的可能性。方法 :采用端粒重复序列扩增法 (telomeraicrepeatamplificationprotocol ,TRAP)来检测 36例乳腺癌及其相应癌旁组织 ,12例良性乳腺病变 ,6例正常乳腺组织中的端粒酶活性。结果 :36例乳腺癌组织中 ,有 33例端粒酶表达阳性 ,其阳性率为 91 7% ,而且与肿瘤的大小 ,淋巴结的状态 ,临床分期有相关性。 36例癌旁组织中 ,有 2例端粒酶表达阳性 ,阳性率为 5 6 %。 12例良性乳腺病变中 ,仅有 1例端粒酶表达阳性 ,阳性率为 8 3%。 6例正常乳腺组织端粒酶表达均为阴性。结论 :乳腺癌组织中普遍存在端粒酶活性表达 ,端粒酶有可能成为诊断乳腺癌的肿瘤标志物。     

Are there differences in breast tissue as a result of hormone replacement therapy? Can BEST imaging distinguish these differences?

Although it has been speculated that estrogen therapy may promote changes in breast tissue that could lead to cancer, no information exists as to differences in breast tissue for women who do and do not take hormone replacement (HRT) therapy. This study seeks to determine if there are differences in the tissue of women taking HRT in contrast to those who do not and if these differences are apparent in cases of breast cancer, cellular atypia, fibrocystic (FCD) disease and normal breasts. A total of 327 non-pregnant, non-lactating, pre-menopausal women were enrolled in the study, including 139 women who were actively taking HRT and 188 women who never had taken HRT. Using breast enhanced scintigraphy test (BEST) imaging, differentiation of breast tissue was determined. The groups were then analyzed to determine the effect of hormone therapy within each category of breast tissue. Differentiation between normal, FCD, cellular atypia, and breast cancer represent statistically significant differences (p.001) in metabolic activity and vascularity as demonstrated by differences in both average count activity (ACA) and maximal count activity (MCA). The distinction between cellular atypia and infiltrating breast cancer was statistically (p.05) different when looking at the maximal activity. Normal breast tissue and breasts with FCD appear more homogenous with no statistical differences in variability in breast tissue. Tissue variability is statistically greater when localized processes, such as cellular atypia and breast cancer, are present. Differentiation of cellular metabolic activity in breast tissue can be statistically determined when looking at the average and maximal metabolic activity. The final distinction between cellular atypia and cancer occurs when a focal region of breast tissue becomes metabolically more active than the surrounding breast tissue as shown by statistical increases in MCA. These findings are confirmed by the increased metabolic variability seen in regions of cellular atypia and cancer compared with the homogenous metabolic activity present in normal and fibrocystic breasts.     

Telomerase activity in ductal carcinoma in situ and invasive breast cancer.

The increasing number of breast carcinoma in situ detected by screening procedures makes it imperative to develop improved markers to stratify the risk of invasive cancer. Telomerase is detectable in invasive cancer, but not in normal tissues. We have microdissected frozen tissue blocks containing both DCIS and invasive cancer to assay the telomerase activity of these two lesions. The 46 available cases of concurrent DCIS and invasive breast cancer resulted in 43 DCIS samples and 38 invasive cancer samples adequate for analysis. Seventy per cent of the DCIS and all invasive cancer samples tested had detectable telomerase activity. In addition, we analysed telomerase activity in ten cases of DCIS that were not associated with invasive cancer, and detected telomerase activity in seven (70%). Mixing experiments showed no evidence of telomerase inhibitors in telomerase negative samples. Furthermore, periductal inflammatory infiltrates were shown to be a potential confounding source of telomerase activity. Since DCIS lesions appear to be heterogeneous with respect to telomerase activity, and telomerase activation appears to precede the development of invasive cancer, telomerase activity may be a useful adjunct in stratifying the risk of developing invasive breast cancer in patients with DCIS.     

乳腺不同病变组织中erbB4的表达及意义

目的　研究erbB4在乳腺不同病变组织中的表达及意义。方法　采用免疫组织化学SP法 ,检测了 3 9例乳腺浸润性导管癌(invasiveductalcarcinoma ,IDC) ,5例纤维腺瘤和 9例小叶增生组织中erbB4蛋白的表达情况。结果　乳腺IDC中erbB4蛋白的阳性表达率为 82 1% ,显著高于纤维腺瘤 (2 0 % )和小叶增生 (4 4 4% ) (P <0 0 5 ) ;乳腺IDC中erbB4蛋白表达情况与淋巴结转移无关 (P>0 0 5 )。结论　erbB4蛋白可能在乳腺IDC的发生中起着促进作用。     

不能触及肿块的多中心乳腺癌：临床病理分析

对１５例无肿块型乳腺癌进行临床及病理分析。这种乳腺癌术前绝大多数被诊断为乳腺增生。其临床特点表现为患者年轻；乳腺触诊无明确肿块，仅表现为区段乳腺增厚；个别病例有乳头溢液，乳腺Ｘ线片可发现腺体内有散在泥沙样钙化，但无肿块影；针吸细胞学检查阳性率低；冰冻切片检查有时也难以作出判断。病理特点主要是癌灶为多灶性的浸润性导管癌；癌灶小，分布广，但只局限在乳腺某一区段内；病变区的腺体都有增生背景。这种类型乳腺癌如能及时发现，预后较好。     

Antigenic cross-reactivity between adenocarcinoma of the breast and fibrocystic disease of the breast.

Peripheral lymphocytes obtained from 12 of 13 patients who had fibrocystic disease (FCD) of the breast were specifically cytotoxic to breast adenocarcinoma cells, as measured in vitro by the microcytotoxicity test. Sera from 6 women with active FCD or metastatic breast cancer could specifically block the cytotoxicity of lymphocytes from either population of patients against cancer cells. This implied extensive antigenic cross-reactivity between benign and malignant hyperplastic disease of the breast. Sera from 4 individuals clinically free of FCD or breast fibroadenoma (FAD) neutralized the blocking activity in the sera of patients with metastatic breast cancer. Patients "cured" of FCD or FAD represented a pool of potential plasma donors for immunotherapy of recurrent breast cancer.