c-erbB-2、p53和Bcl-2蛋白表达在乳腺癌中的意义及其相关性的探讨

目的　探讨乳腺癌中ｃｅｒｂ Ｂ２、ｐ５３ 和Ｂｃｌ２ 蛋白表达与临床病理参数、预后和增殖细胞核抗原（ＰＣＮＡ） 、雌激素受体（ＥＲ）、孕激素受体（ＰＲ）的关系。　方法　应用亲和素生物素复合物（ＡＢＣ） 法免疫组织化学技术对８７例福尔马林固定石蜡包埋的乳腺癌组织进行回顾性研究。　结果　（１）ｃｅｒｂ Ｂ２ 和ｐ５３ 这两种蛋白的超表达与淋巴结转移、病理分级、核分裂、生存期短、ＰＣＮＡ强阳性表达、ＥＲ、ＰＲ阴性表达等不良因素呈正相关趋势（ Ｐ＞ ０－０５） 。（２）Ｂｃｌ２ 的阳性表达与瘤细胞的分化、淋巴结无转移、生存期长,ＥＲ、ＰＲ 的阳性表达等良好因素相关联,而且Ｂｃｌ２的阳性表达常会“减弱”或“抵抗”原癌基因的不良因素。　结论　多种癌基因（ 包括ｃｅｒｂ Ｂ２、ｐ５３ 和Ｂｃｌ２） 参与了乳腺癌的发生和发展     

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。     

淋巴结阴性乳腺癌p21~(waf1)、c-erbB-2和p53蛋白表达及其临床意义

目的：探讨腋淋巴结阴性乳腺癌组织中ｐ２１ｗａｆ１、ｃ－ｅｒｂＢ－２和ｐ５３基因蛋白表达及其与临床病理参数和预后的关系。方法：应用免疫组化ＬＳＡＢ方法检测１２１例腋淋巴结阴性乳腺癌石蜡切片中ｐ２１ｗａｆ１、ｃ－ｅｒｂＢ－２和ｐ５３蛋白的表达情况;同时应用Ｋａｐｌａｎ－Ｍｅｉｅｒ法及多变量Ｃｏｘ比例风险模型,分析３种蛋白表达与预后的关系。结果：（１）ｐ２１ｗａｆ１蛋白表达率为 ４８． ８％,与病理组织学分级、ＥＲ状态有关; ｐ５３蛋白表达率为 ３６． ４％, ｃ－ｅｒｂＢ－２蛋白表达率为 ２６． ４％,与组织学分级有关;（２）ｐ２１ｗａｆ１阳性表达与 ｐ５３表达呈负相关（ Ｐ＜ ０． ０５）;（３）ｐ２１ｗａｆ１阳性组患者无瘤生存率高于阴性组（Ｐ＜０．０５）;ｃ－ｅｒｂＢ－２阳性组患者无瘤生存率明显低于阴性组（Ｐ＜０ ０１）;Ｃｏｘ模型分析显示仅有ｃ－ｅｒｂＢ－２表达对预后有显著影响。结论：乳腺癌组织ｐ２１ｗａｆ１、ｃ－ｅｒｂＢ－２表达与病理组织学分级有相关性;ｐ２１ｗａｆ１表达依赖于ｐ５３途径刺激; ｐ２１ｗａｆ１、、ｃ－ｅｒｂＢ－２表达与腋淋巴结阴性乳腺癌预后有关,且ｃ－ｅｒｂＢ－２表达是一个独立的预后指标。     

Bcl－2癌蛋白的表达与乳腺癌临床和病理某些参数的关系

目的探讨Ｂ细胞淋巴瘤和白血病－２基因（Ｂｃｌ－２）癌蛋白在乳腺癌组织中表达的临床病理意义，方法应用ＬＳＡＢ免疫组织化学法测定１４５例乳腺癌组织中Ｂｃｌ－２蛋白表达。结果Ｂｃｌ－２表达的阳性率为４２．０６％。阳性反应物质位于细胞浆或核膜上，胞核中偶有表达。Ｂｃｌ－２的表达与患者年龄、月经情况、肿瘤大小、淋巴结转移无关，而与预后好的某些病理形态学特征关系密切。在浸润性导管癌不同病理分级组间有明显的差异；核分裂＞２１＞１０ＨＰＦ组中其表达率明显低于０～１０／１０ＨＰＦ组；有肿瘤坏死者的表达率明显低于无肿瘤坏死者。结论Ｂｃｌ－２表达与乳腺癌的生物学行为有关。     

Ｋｉ-６７、ＥＧＦＲ、ＨＥＲ-２和ｐ５３在乳腺癌中的表达及其相关性

目的　分析Ｋｉ-６７、ＥＧＦＲ、ＨＥＲ-２、ｐ５３在乳腺癌组织中的表达,并探讨其与乳腺癌临床病理特征之间的相关性。方法　用免疫组化法检测１３８例乳腺癌患者病理组织中Ｋｉ-６７、ＥＧＦＲ、ＨＥＲ-２和ｐ５３蛋白的表达,并结合临床病理特征进行相关性分析。结果　Ｋｉ-６７、ＥＧＦＲ、ＨＥＲ ２和ｐ５３在乳腺癌组织中的表达率依次为９１.３０％、１７.３９％、６２.３２％和２３.１９％,不同年龄组其表达均无统计学差异（Ｐ＞０.０５）。Ｋｉ-６７的表达与组织学分级、病理类型、肿块大小、淋巴结是否转移及分期显著相关（Ｐ＜０.０５）;ＥＧＦＲ表达与病理类型和ＥＲ状态显著相关（Ｐ＜０.０５）;ＨＥＲ ２表达与病理类型、组织学分级、淋巴结转移、远处转移及分期无相关性（Ｐ＞０.０５）;而ｐ５３表达与组织学分级、ＥＲ和ＰＲ状态呈显著相关（Ｐ＜０.０５）。ＥＲ和ＰＲ呈正相关;ＥＧＦＲ、ＨＥＲ-２、ｐ５３与ＥＲ均为负相关;ＨＥＲ-２和ＰＲ呈负相关;Ｋｉ-６７与ＥＧＦＲ、ＨＥＲ-２、ｐ５３、ＥＲ及ＰＲ之间均无相关性;ｐ５３与ＥＧＦＲ呈正相关;ＥＧＦＲ与ＨＥＲ-２呈负相关。结论　联合检测乳腺癌组织中ＥＧＦＲ、Ｋｉ-６７、ＨＥＲ-２和ｐ５３蛋白的表达能更清楚地了解乳腺癌的生物学行为,对乳腺癌的诊断、指导治疗及评价预后有重要的临床意义。     

ｐ５３、Ｂｃｌ ２、Ｂａｘ、Ｂｃｌ-ｘＬ和Ｂｃｌ-ｘＳ蛋白在胰腺癌中的表达

目的　探讨胰腺癌组织中ｐ５３和Ｂｃｌ-２家族（Ｂｃｌ-２、Ｂａｘ、Ｂｃｌ-ｘＬ、Ｂｃｌ-ｘＳ）蛋白的表达及其与细胞凋亡的关系。方法　免疫组化法检测３５例胰腺癌组织中ｐ５３蛋白表达,分为ｐ５３阴性表达组（１８例）和ｐ５３阳性表达组（１７例）;Ｗｅｓｔｅｒｎｂｌｏｔ法检测胰腺癌组织中ｐ５３、Ｂｃｌ-２、Ｂａｘ、Ｂｃｌ-ｘＬ和Ｂｃｌ-ｘＳ蛋白表达;ＴＵＮＥＬ法检测３５例胰腺癌组织中凋亡指数（ＡＩ）。结果 Ｂｃｌ-２蛋白在ｐ５３阳性表达组上调,而在ｐ５３阴性表达组下调（Ｐ＝０.０４７）;Ｂａｘ和Ｂｃｌ-ｘＬ蛋白在ｐ５３不同表达两组中都明显上调（Ｐ＝０.２７４,Ｐ＝０.３３４）;Ｂｃｌ-ｘＳ在ｐ５３阳性表达组明显下调,在ｐ５３阴性表达组明显上调（Ｐ＝０.０１）;在ｐ５３不同表达两组中,ＡＩ分别为１２.１±２.４７和９.１±１.４８（Ｐ＝０.０２３）;上述Ｂｃｌ-２家族各成员表达与ＡＩ无相关性（Ｐ＞０.０５）,而ｐ５３不同表达Ｂｃｌ-２／Ｂａｘ比值与ＡＩ有明显的相关性（Ｐ＜０.０１）。结论　Ｂｃｌ-２是依赖ｐ５３调节的抗凋亡蛋白,Ｂｃｌ-ｘＳ是依赖ｐ５３调节的促凋亡蛋白,而ｐ５３主要通过调节Ｂｃｌ ２／Ｂａｘ比值发挥凋亡调节作用。     

ＡｈＲ在乳腺癌组织中的表达及其与预后相关性的研究

目的　探讨芳香烃受体（ＡｈＲ）在原发性乳腺癌组织中的表达情况及其与预后的关系。方法　收集６４例原发性乳腺癌患者的临床病理资料并随访,中位随访时间７０.４个月。采用免疫组化ＥｌｉＶｉｓｉｏｎ法检测乳腺癌组织中ＡｈＲ、Ｃ-ｅｒｂＢ２及ｐ５３的表达情况,分析ＡｈＲ与年龄、淋巴结转移数目、雌激素受体（ＥＲ）、孕激素受体（ＰＲ）、Ｃ-ｅｒｂＢ２、ｐ５３等因子以及预后的关系。结果　６４例原发性乳腺癌ＡｈＲ的阳性表达率为２６６％（１７／６４）。ＡｈＲ表达与Ｃ ｅｒｂＢ２表达呈正相关（Ｐ＝０.０１７）,经ＥＲ分层后,仅ＥＲ阴性患者上述两者有相关性（Ｐ＝０.００６）。单因素分析表明,ＡｈＲ阳性表达乳腺癌患者的无病生存时间（ＤＦＳ）较短（Ｐ＝０.０２６）;多因素分析表明,ＡｈＲ是乳腺癌患者预测ＤＦＳ的独立因素（Ｐ＝０.０４９）,也是影响总生存时间（ＯＳ）的危险因素（ＨＲ＝２.４４８Ｐ＝０.０８）。经分层分析,ＥＲ阴性乳腺癌患者中ＡｈＲ阳性表达者预后更差。结论　ＡｈＲ是预测原发性乳腺癌患者预后的独立因素,尤其在ＥＲ阴性乳腺癌中,ＡｈＲ阳性表达提示患者预后差。     

乳腺癌c—erbB—2,表皮生长因子受体基因蛋白表达与预后的关系

以免疫组化ＡＢＣ法检测乳腺癌ｃ－ｅｒｂＢ－２、表皮生长因子受体基因蛋白表达，研究其与预后的关系，结果：ｃ－ｅｒｂＢ－２、ＥＧＦＲ阳性表达率各为３８．５％（２５／６５）和４３．１％（２８／６５）。除ＥＧＦＲ表达与ＥＲ、ＰＲ负相关外，ｃ－ｅｒｂＢ－２，ＥＧＦＲ表达与临床预后因素无相关性，二者之间亦无相关性。ｃ－ｅｒｂＢ－２或ＥＧＦＲ阳性组术后生存显著差于阴性组（Ｐ〈０．０１）；多因素分析二者是显著影响     

乳腺癌中bcl—2的表达与激素受体的相产性

目的 探讨ｂｃｌ－２估人原发性乳腺癌中的表达及与激素受体的相关性。方法 利用免疫组织化学（ＨＣ）方法，检测１８０例人原发性乳腺癌组织中ｂｃｌ－２的表达及与ＥＲ，ＰＲ激素受体的相关性。结果 乳腺癌中ｂｃｌ－２，ＥＲ和ＰＲ的阳性符合率分别为５７．７８％（１０４／１８０），５２．２２％（９４／１８０）和３８．８９％（７０／１８０）。     

核因子-κＢ在三阴性乳腺癌中的表达及其意义

目的　探讨核因子-κＢ（ＮＦ-κＢ）在三阴性乳腺癌组织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ＰＶ-６０００二步法检测１３７例三阴性乳腺癌和１３２例非三阴性乳腺癌患者癌组织ＮＦ-κＢ的表达,分析其与临床病理特征和预后之间的关系。结果　１３７例三阴性乳腺癌组织中的ＮＦ-κＢ阳性表达率为７３.７％（１０１／１３７）,明显高于非三阴性乳腺癌的４６.２％（６１／１３２）,差异有统计学意义（Ｐ＝０.０００）。在１３７例三阴性乳腺癌中,ＮＦ-κＢ表达与ＶＥＧＦ、ｐ５３、组织分级、淋巴结转移、５年无病生存率和５年总生存率有关（Ｐ＜０.０５）;而在１３２例非三阴性乳腺癌中,ＮＦ-κＢ表达仅与ＶＥＧＦ、淋巴结转移、５年无病生存率相关（Ｐ＜０.０5）。结论　ＮＦ-κＢ在三阴性乳腺癌中表达率高,并可作为三阴性乳腺癌的预后指标。     

乳腺肿物Bcl—2表达与激素调节的相关研究

用免疫组化方法，观察乳腺癌及良性病变是否有Bcl－2表达；Bcl－2表达及丧失与激素受体的相关性；Bcl－2表达与肿瘤分级的关系等。结果发现Bcl－2表达与ER、PR、肿瘤组织分级显著相关，Bcl－2表达阳性的乳腺癌多伴有ER＋（75％）、PR＋（70％），而Bcl－2阴性表达与预后较差的分子标志呈正相关，即ER、PR阴性率高、组织分级高。我们的发现支持了乳腺癌Bcl-2表达受激素调节的假说。     

Different Prognostic Factors Correlate with Bcl-2 Expressionamong Triple Negative and Non-Triple Negative Breast Cancers

Background: Prognostication of breast cancer using clinico-pathologic variables, although useful, remainsimperfect. Recent research has focused on finding new markers of prognosis using gene expression profiling.Panels of proteins assessed by immunohistochemistry might also be useful in this regard. This study focusedon Bcl-2 protein expression in triple-negative (TNBC) and non- triple-negative breast cancer (non-TNBC) withcorrelation to clinico-pathologic variables. Materials and methods: We analyzed Bcl-2 expression in 77 womenwith primary breast carcinoma divided into two groups; triple-negative and non- triple-negative according toexpression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptors (Her2/neu). Bcl-2expression was assessed in relation to age, histo-pathological subtype, grade, nodal status and tumor size. Results:Bcl-2 was expressed in 74% of triple-negative breast cancers and 70% of non- triple-negative cancers. In TNBC,expression was significantly correlated with invasive ductal subtype, while in non-TNBC it was significantlycorrelated with age and negative nodal status. In both groups higher Bcl-2 expression associated with favourableprognostic factors in breast cancer, but no significant statistical correlations were found. Conclusions: Frequencyof Bcl-2 expression does not differ between TNBC and non-TNBC, but different prognostic factors correlatewith Bcl-2 in the two cases.     

乳腺癌组织中上皮钙黏蛋白和B细胞淋巴瘤基因2的表达及其临床意义的研究

目的:探讨乳腺癌中上皮钙黏蛋白（E-cadherin）和B细胞淋巴瘤基因2（Bcl-2）的表达及其临床意义。方法:使用免疫组织化学方法检测68例乳腺癌旁正常组织、41例纤维腺瘤组织和74例乳腺癌组织的E-cadherin和Bcl-2的表达水平,并分析乳腺癌患者各病理特征与E-cadherin和Bcl-2表达的相关性。结果:乳腺癌旁正常组织和纤维腺瘤组织中E-cadherin阳性率高于乳腺癌组织,Bcl-2阳性率低于乳腺癌组织,差异具有统计学意义（P均＜0.05）。乳腺癌组织病理分级越高、TNM分期越严重、有淋巴结转移和复发的患者 E-cadherin阳性率低,Bcl-2阳性率高;ER阳性患者E-cadherin阳性率高,Bcl-2阳性率高。组织病理分级低-中分化患者E-cadherin阳性率高于高分化患者,Bcl-2阳性率低于高分化患者,差异具有统计学意义（P均＜0.05）;TNM分期Ⅰ+Ⅱ期患者E-cadherin阳性率高于Ⅲ期,Bcl-2阳性率低于Ⅲ期,差异具有统计学意义（P均＜0.05）;有淋巴结转移患者E-cadherin阳性率低于无转移者,Bcl-2阳性率高于无转移者,差异具有统计学意义（P均＜0.05）;雌激素受体（ER）阴性患者E-cadherin、Bcl-2阳性率低于ER阳性者,差异具有统计学意义（P均＜0.05）;复发患者E-cadherin阳性率低于无复发者,Bcl-2阳性率高于无复发者,差异具有统计学意义（P均＜0.05）;Bcl-2的表达与E-cadherin的表达存在负相关性（r=-0.638,P＜0.05）。结论:乳腺癌组织中E-cadherin表达降低,Bcl-2表达升高,二者与乳腺癌组织病理分级、TNM分期、淋巴结转移、ER和复发有关,E-cadherin和Bcl-2的表达存在相关性。     

Bcl-2 antigen expression in luminal A and triple-negative breast cancer

Biomarkers for the prognosis of breast cancer have been routinely used in clinical practice, including the expression of hormone receptors, Ki-67 and HER-2. More recently, Bcl-2 has been recognized as an important prognostic factor in breast cancer, although controversies persist with respect to the significance of its expression. The aim of the present study was to evaluate Bcl-2 antigen expression in luminal A and triple-negative breast cancer. Sixty women with invasive ductal carcinoma were included in the study and divided into two groups: Group A (luminal A) and Group B (triple-negative), with 30 cases in each group. Immunohistochemistry was performed on tissue sections to evaluate Bcl-2 antigen expression. Fisher’s exact test was used to compare the proportions of cases with cells expressing Bcl-2 between the two subtype cancer groups, with statistical significance being established at p < 0.05. The number of cases with cells expressing Bcl-2 in Groups A and B was 26 (86.7%) and 12 (40.0%), respectively (p < 0.0003). In the present study, the expression of the anti-apoptotic protein Bcl-2 was greater in luminal A breast cancer tissue samples compared to triple-negative breast cancer.     

Clinical significance of bcl-2 gene expression in human breast cancer tissues

The expression of estrogen receptor (ER) and bcl-2(Bcl-2), an apoptosis protective oncogene, in normal andcancerous breast duct epithelia was immunohistochemically examined infresh frozen tumor tissues from 142 Japanese breastcancer patients. The clinico-pathological characteristics and the diseasefree survival of the patients were analyzed. Theexpression of both the proteins was also observedin intraductal components of breast cancer. Although lessthan 1% of normal duct epithelia expressed ER,Bcl-2 was diffusely expressed. The expression of boththese proteins in breast cancer significantly correlated witheach other. Their expression significantly correlated negatively withtumor size but not with lymph node status.The papillo-tubular sub-type of invasive ductal carcinoma expressedBcl-2 significantly more frequently than the solid-tubular sub-type.Patients with Bcl-2 expressing tumors survived without recurrencesignificantly more than those with tumors exhibiting reducedexpression. Papillary-cribriform type intraductal componentsexpressed both those proteins more often than the solid-comedo type.     

ERα and ERβ expression in correlation with Ki-67, Bcl-2 and Bak in primary tumors and lymph node metastases of breast cancer: The effect of pre-operative chemotherapy

This study aimed to assess the pre-operative chemotherapy impact on the relationship between estrogen receptor (ER) expression and markers of proliferation and apoptosis in primary and metastatic breast cancer. Immunohistochemical examinations were conducted on surgically removed ductal invasive breast cancers and their lymph node metastases in 135 patients. A total of 64 patients from this group underwent pre-operative chemotherapy and in 71 cases the surgery was performed without primary chemotherapy. A negative correlation between ERα and Ki-67 was found in primary tumors and lymph node metastases. A positive correlation was observed between ERα and Bcl-2. A positive correlation was also noted between ERβ and Bak, suggesting that the two ERs were involved in the regulation of proteins responsible for the control of the apoptotic process. Assessment of the expression of the proteins conducted separately in primary tumors and lymph node metastases did not reveal a significant effect of pre-operative chemotherapy on the correlations of ERs with Ki-67, Bcl-2 and Bak. However, the analysis of the correlations between the receptor expression in primary tumors and Ki-67, Bcl-2 and Bak in lymph node metastases showed a statistically significant impact of pre-operative chemotherapy on the correlations of ERα and Bcl-2 with ERβ and Bak, confirming involvement of the two ERs in the regulation of apoptosis during breast carcinogenesis.     

Bcl-2 expression in breast cancer is down-regulated by trans-arterial administration of chemotherapeutic agents

Bcl-2 is one of the cytoplasmic oncoproteins, and has been shown to suppress apoptotic cell death. In this study, we investigated the relationship between Bcl-2 expression and effects of chemotherapeutic agents on human breast cancer cells. We examined 26 surgically resected breast tumors with preoperative trans-arterial administration of chemotherapeutic agents and 30 control cases using immunohistochemical methods. In all 26 cases in the chemotherapy group, the breast cancer cells were focally degenerated to various degrees, associated with inflammation and stromal desmoplastic changes. Bcl-2 expression was found in 46% (12/26) of the chemotherapy group and in 67% (20/30) of controls. Of the 12 Bcl-2-positive cases in the chemotherapy group, 5 were diffusely positive [Bcl-2(2+)] and 7 were focally positive [Bcl-2(+)]. Of the 20 Bcl-2-positive cases in the control group, 18 were diffusely positive and 2 were focally positive. We speculate that Bcl-2 expression was down-regulated by trans-arterial administration of chemotherapeutic agents and was associated with apoptosis and degeneration of breast cancer cells.     

BP1在乳腺癌组织中的表达及临床意义

目的探讨BP1与乳腺癌临床病理因素的关系及与Bcl-2表达的相关性。方法运用Western blot及免疫组织化学方法检测45例乳腺癌组织和相应癌旁组织中BP1以及乳腺癌组织中Bcl-2、ER、PR、C-erbB-2的蛋白表达。结果乳腺癌组织中BP1蛋白阳性表达水平及阳性细胞数均高于相应癌旁组织,差异均有统计学意义(P均<0.05)。乳腺癌组织中BP1蛋白表达水平与Bcl-2蛋白表达水平呈正相关关系(r=0.678,P<0.05);乳腺癌组织中BP1蛋白阳性细胞数与Bcl-2阳性细胞数呈正相关关系(r=0.653,P<0.05)。BP1高表达与ER、PR及C-erbB-2有关(P均<0.05)。结论 BP1蛋白可能具有促进乳腺癌发生、发展的作用,这可能与其上调Bcl-2表达进而抑制乳腺癌细胞凋亡有关。     

Analysis of clinically relevant values of Ki-67 labeling index in Japanese breast cancer patients

Background

It has become important to standardize the methods of Ki-67 evaluation in breast cancer patients, especially those used in the interpretation and scoring of immunoreactivity. Therefore, in this study, we examined the Ki-67 immunoreactivity of breast cancer surgical specimens processed and stained in the same manner in one single Japanese institution by counting nuclear immunoreactivity in the same fashion.

Methods

We examined 408 Japanese breast cancers with invasive ductal carcinoma and studied the correlation between Ki-67 labeling index and ER/HER2 status and histological grade of breast cancer. We also analyzed overall survival (OS) and disease-free survival (DFS) of these patients according to individual Ki-67 labeling index.

Results

There were statistically significant differences of Ki-67 labeling index between ER positive/HER2 negative and ER positive/HER2 positive, ER negative/HER2 positive or ER negative/HER2 negative, and ER positive/HER2 positive and ER negative/HER2 negative groups (all P < 0.001). There were also statistically significant differences of Ki-67 labeling index among each histological grade (P < 0.001, respectively). As for multivariate analyses, Ki-67 labeling index was strongly associated with OS (HR 39.12, P = 0.031) and DFS (HR 10.85, P = 0.011) in ER positive and HER2 negative breast cancer patients. In addition, a statistically significant difference was noted between classical luminal A group and “20 % luminal A” in DFS (P = 0.039) but not between classical luminal A group and “25 % luminal A” (P = 0.105).

Conclusions

A significant positive correlation was detected between Ki-67 labeling index and ER/HER2 status and histological grades of the cases examined in our study. The suggested optimal cutoff point of Ki-67 labeling index is between 20 and 25 % in ER positive and HER2 negative breast cancer patients.     

乳腺癌雌孕激素水平及其受体和c-erbB-2癌基因表达的临床意义

目的 :研究乳腺癌雌孕激素水平、雌孕激素受体及c erbB 2癌基因蛋白的表达情况及其临床意义。方法 :分别应用12 5I放射免疫组化ABC法研究了 82例乳腺癌和 6 8例乳腺良性病变患者血清雌孕激素水平以及病变组织雌孕激素受体、癌基因c erbB 2的表达。结果 :乳腺癌组的雌激素水平和癌基因c erbB 2的表达率明显高于良性病变组 ,雌激素水平与腋淋巴结状况呈明显正相关。ER、PR的表达与腋淋巴结状况关系不大 ,但与临床分期呈明显负相关 ,ER的阳性表达者 5年无瘤生存率明显高于复发或死亡者。癌基因c erbB 2的阳性表达率与临床分期及远期生存率呈显著正相关。结论 :雌孕激素水平高、癌基因c erbB 2的阳性表达是乳腺癌预后不良的指标 ,ER、PR的阳性表达是乳腺癌预后良好的指标 ,对乳腺癌的诊断治疗和预后判断具有重要的指导意义。