肝细胞癌中血管内皮生长因子及其受体的表达与意义

目的 :探讨血管内皮生长因子(VEGF)和血管内皮生长因子受体 (VEGFRs)在肝细胞癌 (HCC)肿瘤血管生成中的调节作用。方法 :采用免疫组化法检测 3 9例 (男 3 4例 ,女 5例 )共 41个经手术病理证实的HCC病灶VEGF、Flt 1和KDR/Flk 1的蛋白表达。观察病灶肿瘤大小、包膜、子灶、门静脉癌栓、肝门淋巴结转移和肝硬化等。记录HCC患者的临床资料 ,如年龄、HBsAg、HBV和AFP情况。手术结果记录病灶大小、数目、肝硬化和包膜情况。病理结果记录病理分级、肝硬化等情况。结果 :在转移高危组、包膜欠完整和 (或 )无包膜组、小肝癌组中VEGF表达阳性率均高于转移低危组、包膜完整组和大肝癌组 ,差异有统计学意义 ,P <0 0 5。而VEGF的表达与Ed mondson分级、HBV、HBsAg、AFP水平以及肝硬化之间差异均无统计学意义 ,P >0 0 5。KDR/Flk 1表达阳性病灶 2 9个 ,阳性率为 70 73 %( 2 9/4 1) ;KDR/Flk 1在转移高危组、包膜欠完整和 (或 )无包膜组、小肝癌组中表达的阳性率也均高于转移低危组、包膜完整组和大肝癌组 ,差异有统计学意义 ,P <0 0 5。KDR/Flk 1蛋白的表达亦与Edmondson分级、HBV、HBsAg、AFP水平、肝硬化之间差异无统计学意义 ,P >0 0 5。Flt 1阳性病灶 2 8个 ,阳性率为 68 2 9% ( 2 8/4 1) ;Flt 1的表达与转移     

Expression of vascular endothelial growth factor and its receptors during lung carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine in rats.

The expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), VEGFR-1/Flt-1 and VEGFR-2/Flk-1, was investigated by immunohistochemical and northern blot analysis during lung carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine (BHP) in male Wistar rats. After BHP was given in the drinking water for 12 wk, the rats were maintained without further treatment until they were killed at 20-28 wk. Immunohistochemical studies revealed VEGF expression in almost all malignancies, the reaction being strongly positive in most adenocarcinomas (15 of 18; 83.3%) and squamous cell carcinomas (four of five; 80.0%), but less so in a total of 120 adenomas and 136 alveolar hyperplasias. In addition, VEGF mRNA and VEGFR mRNAs were found to be overexpressed in most adenocarcinomas and squamous cell carcinomas as well as in one to three of the five adenomas tested. The results indicated that VEGF and VEGFRs play important roles in the acquisition of malignant potential by preneoplastic lung lesions induced by BHP in rats. Moreover, overexpression of VEGF was related to upregulation of VEGFR-1/Flt-1 and VEGFR-2/Flk-1 expression in malignant and premalignant lung lesions.     

ER PR 单阳性表达乳腺癌患者临床病理特征和预后分析*

目的:探讨不同的ER、PR表达对原发性侵袭性乳腺癌患者预后的影响,重点研究ER+/PR- 和ER-/PR+ 单阳性表型肿瘤的临床病理特征和预后差异。方法:回顾性分析1998年10月至2004年5 月间天津医科大学附属肿瘤医院收治的1 054 例原发性侵袭性乳腺癌患者的病例资料及随访结果,比较不同的ER、PR表达乳腺癌患者的临床病理特征和预后,明确ER+/PR- 和ER-/PR+ 单阳性表型肿瘤之间存在的差异。计算生存率采用Kaplan-Meier 方法,生存率比较应用Log-rank 检验。经COX多因素分析得出独立的预后影响因素。结果:ER+/PR- 表型肿瘤易出现于年长、绝经后的女性,肿瘤直径较小,组织分化程度较高。生存分析显示:ER+/PR+ 组预后优于ER-/PR- 组（OS:P=0.000,DFS :P=0.000）,ER或PR单阳组预后介于ER+/PR+ 组和ER-/PR- 组之间。相对于ER-/PR- 表型肿瘤,ER+/PR- 的生存优势强于ER-/PR+ ,ER+/PR- 的无瘤生存优于ER-/PR+（P=0.035）,而两者之间总体生存无明显差异（P=0.890）。 不同的ER、PR阳性表达是影响乳腺癌患者内分泌治疗的无瘤生存的独立因素（P=0.023）。 结论:ER+/PR- 和ER-/PR+ 是两种临床病理特征和预后完全不同的乳腺癌,ER-/PR+ 肿瘤表现的侵袭性行为更强,应该采取更为积极的治疗措施。ER-/PR+ 表型乳腺癌可能具有独特的生物学特征。      

Expression and localization of vascular endothelial growth factor receptors in human hepatocellular carcinoma and non-HCC tissues

Flt-1 (VEGF receptor-1) and KDR/Flk-1 (VEGF receptor-2) are the high-affinity receptors for the angiogenesis factor, vascular endothelial growth factor (VEGF). VEGF expression has been confirmed in human hepatocellular carcinoma (HCC), and VEGF is thought to be involved in the angiogenesis within HCC tissues. However, expressions of VEGF receptors in HCC have not been reported. We immunohistochemically examined expressions and localizations of Flt-1 and KDR in 28 surgically resected HCC tissues. In non-cancerous area, Flt-1 and KDR were mainly found in macrophages including Kupffer cells; both receptors were found in vascular endothelial cells in the portal veins and arteries within portal tracts; and KDR was also found in some sinusoidal endothelial cells. In cancerous area, Flt-1 and KDR were found in some macrophages, and also in the endothelial cells of intratumoral blood vessels. In 25 moderately and/or poorly differentiated HCCs, KDR expression in the blood space endothelial cells was clear and continuous in 20 cases, and focal in 5 cases. These results suggest that there would be an angiogenesis mechanism via VEGF/Flt-1 or VEGF/KDR in HCC, and the VEGF/KDR system would take a more important role.     

EGFR、VEGFR1/Flt-1在未放疗和放疗后食管鳞癌组织中的表达

目的：探讨食管鳞癌组织中内皮生长因子受体（EGFR）、血管内皮生长因子受体1（VEGFR1/Flt-1）的表达与术前辅助放疗敏感性的关系。方法：采用免疫组织化学染色方法（EnVision二步法）检测40例未接受放疗和40例接受放疗后手术切除的食管鳞癌组织,以及20例切除组织的上切缘正常组织中EGFR、VEGFR1/Flt-1的表达。结果：EGFR在正常组织中无表达,在未接受放疗食管鳞癌中的表达率为77.5%,在接受放疗后食管鳞癌中的表达率为70%,EGFR在放疗后食管鳞癌中的表达与未放疗食鳞癌的表达相比,经卡方检验其差异具有统计学意义（P〈0.05）。VEGFR1/Flt-1在正常组织中阳性表达率为80%,在未接受放疗食管鳞癌中的表达率为62.5%,在接受放疗后食管鳞癌中的表达率为80%,VEGFR1/Flt-1在放疗后食管鳞癌中的表达与未放疗食管鳞癌的表达相比较,经卡方检验其差异具有统计学意义（P〈0.05）。结论：检测EGFR、VEGFR1/Flt-1有助于预测食管鳞癌术前放疗的疗效。     

卵巢上皮癌细胞中VEGF和VEGFRs的表达与STATs的活化

目的　研究卵巢上皮癌细胞中血管内皮生长因子 (VEGF)、血管内皮生长因子受体(VEGFRs)的表达与血管内皮细胞内的信号转导和转录活化因子 (STATs)的活化及其相关性 ,并阐明VEGF对卵巢癌细胞的直接作用及机制。方法　选择 4 2例卵巢上皮性癌患者作为研究对象 ,2 9例卵巢良性肿瘤患者和 11例正常卵巢组织作为对照 ,用免疫组织化学LSAB法检测组织中VEGF、VEGFRs、STATs蛋白的表达 ,并进行半定量及相关性分析。结果　 (1)VEGF定位于胞浆 ,VEGFRs定位于胞浆和胞膜。VEGF在卵巢癌细胞呈高表达 ,VEGFRs在卵巢癌细胞及间质血管内皮细胞中均呈高表达 ,与良性及正常对照组差异有统计学意义 (P <0 .0 1)。 (2 )P STATs定位于胞浆和胞核。在卵巢癌细胞及血管内皮细胞中 ,P STAT3和P STAT5高表达 ,与两对照组相比 ,差异有统计学意义 (P <0 .0 1) ;P STAT1、P STAT6低表达 ,各组间差异无统计学意义。 (3)在血管内皮细胞中 ,VEGFR1的表达与P STAT5呈正相关 (r =0 .2 4 3) ,而VEGFR2与P STAT3呈正相关 (r =0 .30 8) ;在卵巢癌细胞中 ,VEGF、VEGFR1、VEGFR2与P STAT3、P STAT5之间均呈正相关 ,而与P STAT1、P STAT6无相关。结论VEGF可直接作用于卵巢上皮癌细胞 ,STATs可能参与了VEGF细胞内的信号传导。     

Expression of VEGFR3 in glioma endothelium correlates with tumor grade

Angiogenic processes are regulated by vascular endothelial growth factors (VEGFs) and their receptors VEGFR1 (Flt-1), 2 (Flk-1) and 3 (Flt-4). While VEGFR2 is thought to play a central role in tumor angiogenesis, anti-angiogenic therapies targeting VEGFR2 in glioma models can show escape phenomena with secondary onset of angiogenesis. The purpose of this study was to find explanations for these processes by searching for alternative pathways regulating glioma angiogenesis and reveal a correlation with tumor grade. Thus, VEGFR3, which is not expressed in normal brain, and its ligands VEGF-C and -D, were assessed in high grade (WHO°IV, glioblastomas, GBM) and low grade gliomas [WHO°II astrocytomas (AII)]. In all GBM, a strong protein expression of VEGFR3 was found on tumor endothelium, VEGF-C and -D expression was found on numerous cells in areas of high vascularization. On RNA level, a significant up-regulation of VEGFR3 was detected in GBM compared to AII and non-neoplastic brain. In AII, only very moderate VEGFR3, VEGF-C and -D expression was found on protein and RNA level indicating a correlation of VEGFR3 expression with tumor grade. VEGFR3 signal in both grades was found predominantly on endothelial cells, confirmed by VEGFR3 expression on isolated CD31 positive cells and the expression of various endothelial markers on VEGFR3-positive cells isolated from GBM. The demonstration of a complete angiogenic signaling system that is dependent on tumor grade may influence the traditional paradigm of glioma angiogenesis and may provide a basis for more effective anti-angiogenic treatment strategies.     

Vasohibin-1 in human breast carcinoma: A potential negative feedback regulator of angiogenesis

Vasohibin-1 is a recently identified negative feedback inhibitor or suppressor of angiogenesis induced by vascular endothelial growth factor (VEGF)-A. The status of vasohibin-1 in human breast carcinoma has not been examined. We examined 151 breast specimens including 98 cases of invasive ductal carcinoma (IDC), 12 of ductal carcinoma in situ (DCIS), 16 of fibroadenoma (FA), six of inflammatory lesion, nine of fibrocystic change and seven of non-pathological breast tissue. We immunolocalized vasohibin-1 and compared its immunoreactivity to that of VEGF-A, basic fibroblastic growth factor (bFGF), VEGF receptor 2 (Flk-1), CD31, CD34 and Ki-67/MIB-1. The correlation of vasohibin-1 immunoreactivity with overall survival (OS), and disease-free survival (DFS) of the patients with breast carcinoma was also evaluated. In addition, we evaluated Ki-67 and CD31, and Ki-67 and vasohibin-1 double-immunostaining for further characterization of neovascularization. Vasohibin-1 was detected in endothelial cells of human breast and its immunodensity was significantly higher in IDC and inflammatory lesions than the other types ( P <  0.001). In addition, a significant positive correlation was detected between vasohibin-1 and VEGF-A, bFGF or Flk-1 ( P <  0.001). There was also positive association s between vasohibin-1 and OS ( P  = 0.004) and between vasohibin-1 and DFS ( P ≤ 0.001 ) in carcinoma cases. Results of double-immunostaining demonstrated the ratio of Ki-67-positive cells among vasohibin-1-positive endothelial cells (46.5%) was significantly higher than those among CD31-positive cells (23.5%). This is the first study demonstrating the status of vasohibin-1 in human breast lesions, which indicates that vasohibin-1 is associated with neovascularization and may especially play important roles in the regulation of intratumoral angiogenesis in human breast cancer. ( Cancer Sci 2009; 100: 88–94)     

DUSP6在肝细胞肝癌中的表达与MAPK信号通路及临床病理学特征相关性研究

  目的  探讨DUSP6在肝细胞肝癌（hepatocellular carcinoma,HCC）中的表达及其与MAPK信号通路和临床病理学特征相关性。  方法  查询复旦大学附属中山医院肝癌研究所2005年1月至2006年12月HCC临床病理资料数据库,筛选出305例HCC制作组织芯片,免疫组化检测DUSP6、p-ERK、p-JNK、p-P38α、CyclinD1和Ki-67表达,将以上结果同临床病理学特征进行统计学相关性分析。  结果  HCC肿瘤组织、癌旁组织和正常肝组织DUSP6表达存在显著性差异（P < 0.001）;p-ERK、p-JNK和Ki-67肿瘤组织与癌旁组织表达存在显著性差异（P < 0.001）。Spearman相关性分析,在HCC肿瘤组织中DUSP6和p-ERK,CyclinD1及Ki-67的表达呈显著正相关（r=0.179,P < 0.01;r=0.213,P < 0.01;r=0.137,P < 0.05）。相对癌旁,各组肿瘤组织DUSP6表达、有乙肝和肝硬化病史者不同分组间均存在显著性差异（P < 0.05）。  结论  DUSP6在HCC中肿瘤组织较癌旁组织和正常肝组织过表达,DUSP6对p-ERK过表达可能起负反馈调节作用。DUSP6过表达可能与HCC细胞周期调节及促进肿瘤增殖活性有关。      

Dickkopf-1 promotes angiogenesis by upregulating VEGF receptor 2-mediated mTOR/p70S6K signaling in hepatocellular carcinoma

The expression of Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling pathway, is upregulated in hepatocellular carcinoma (HCC). Here, we investigated the tumorigenic and angiogenic potential of DKK1 in HCC. Stable cell lines were established using the clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9)-based DKK1 knock-out system in Hep3B cells and the tetracycline-based DKK1 inducible system in Huh7 cells. Multicellular tumor spheroids (MCTSs) were cultured using Hep3B stable cells. We also employed xenografts generated using Hep3B stable cells and transgenic mouse models established using hydrodynamic tail vein injection. The angiogenic potential increased in HUVECs treated with CM from Huh7 stable cells with high DKK1 expression and Hep3B wild-type cells. DKK1 accelerated the downstream molecules of vascular endothelial growth factor receptor 2 (VEGFR2)-mediated mTOR/p70 S6 kinase (p70S6K) signaling. MCTSs generated using Hep3B wild-type cells promoted compact spheroid formation and increased the expression of CD31 and epithelial-mesenchymal transition (EMT) markers, and increased the VEGFR2-mediated mTOR/p70S6K signaling, compared to the controls (all P<0.01). Xenograft tumors generated using Hep3B cells with DKK1 knock-out (n=10) exhibited slower growth than, the controls (n=10) and the expression of Ki-67, VEGFR2, CD31 and EMT markers decreased (all P<0.05). In addition, forced DKK1 expression with HRAS in transgenic mouse livers (n=5) resulted in the formation of more tumors and increased expression of downstream molecules of VEGFR2-mediated mTOR/p70S6K signaling pathway as well as Ki67, CD31 and EMT markers (P<0.05), compared to that of the controls (n=5). Our findings indicate that DKK1 facilitates angiogenesis and tumorigenesis by upregulating VEGFR2-mediated mTOR/p70S6K signaling in HCC.     

Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2 (KDR/Flk-1) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice

Vascular endothelial growth factor (VEGF) is a multifunctional angiogenic growth factor that is a primary stimulant of the development and maintenance of a vascular network in embryogenesis and the vascularization of solid tumors. At the present time there are two well-characterized receptors for VEGF that are selectively expressed on endothelium. VEGF receptor 2 [VEGFR2 (KDR/Flk-1)] mediates endothelial cell mitogenesis and permeability increases, whereas the role of VEGF receptor 1 [VEGFR1 (Flt-1)] has not been clearly defined. In the present study, a monoclonal antibody, 2C3, is shown to block the interaction of VEGF with VEGFR2 but not with VEGFR1 through ELISA, receptor binding assays, and receptor activation assays. 2C3 blocks the VEGF-induced vascular permeability increase in guinea pig skin. 2C3 has potent antitumor activity, inhibiting the growth of newly injected and established human tumor xenografts in mice. These findings demonstrate the usefulness of 2C3 in dissecting the pathways that are activated by VEGF in cells that express both VEGFR1 and VEGFR2, as well as highlighting the dominant role of VEGFR2 in mediating VEGF-induced vascular permeability increase and tumor angiogenesis.     

Relationship between the Expression of VEGF, FIk-1 and Fit-1 Proteins and Clinicopcrthology in Hepatocellular Carcinoma

Objective To study the relationship between the expression of VEGF, Flk-1 and Flt-1 proteins and clinical pathology in hepatocellular carcinoma. Methods The expression of VEGF, Flk-1 and Flt-1 proteins in hepatocellular carcinomas from 60 patients was determined by immunohistochemistry (ABC method) and VEGF expression in relation to the clinicopathology evaluated. Results The positive rates of VEGF, Flk-1 and Flt-1 protein expression were 81.3%, 88.3%, 80.0% in tumor tissues, respectively, rates which were significantly higher than those in normal liver tissue (P<0.05). The expression of VEGF protein was correlated with the histologic grade and metastases of the tumors. Conclusion The results showed that, in hepatocellular carcinoma, a higher expression of VEGF protein was associated with a higher degree of malignancy and a greater tendency for metastases. VEGF, Flk-1 and Flt-1 play an important role in tumourgenesis. The project was funded by the Tianjin Natural Science Grant (No. 01361561).     

Both cell proliferation and apoptosis significantly predict shortened disease-free survival in hepatocellular carcinoma

In this study, we investigated the proliferating cell index by the percentage of Ki-67 expressing cells (Ki-67 LI) and the apoptotic index (AI) by the number of morphologically apoptotic cells per 1000 carcinoma cells in haematoxylin and eosin sections of 76 hepatocellular carcinomas (HCC). Both indices showed excellent correlation with each other (P < 0.0001) and were significantly higher in cases of poor differentiation, of advanced stages, with portal invasion and with intrahepatic metastasis. Furthermore, cases with higher Ki-67 LI or higher AI displayed poor outcomes for disease-free survival (P = 0.0001 and P = 0.0005) by univariate analysis. By multivariate analysis, both indices could be regarded as independent prognostic factors. These results strongly suggest that Ki-67 LI and AI have very similar clinical significance, reflecting the existence of biologically aggressive phenotypes and poor disease-free survival rate in HCC.     

Proliferative marker Ki-67 in gallbladder carcinomas: high expression level predicts early recurrence after surgical resection.

To evaluate the prognostic value of proliferative maker Ki-67, its expression was determined immunohistochemically in 37 gallbladder carcinomas (GBCs). A high Ki-67 index was significantly correlated with tumor lymphatic invasion (P=0.007) and vascular invasion (P=0.04). High Ki-67 index group and low Ki-67 index group showed different clinical courses. Five patients who experienced recurrences in high Ki-67 index group developed their recurrent diseases within one year after surgery and died soon after recurrence, while the recurrences (five cases) in low Ki-67 index group were distributed all stages after surgery. In conclusion, high Ki-67 index predicts early recurrence after surgery for GBCs.     

乳腺浸润性小叶癌组织Ki-67表达与临床病理特征相关性分析

目的 浸润性小叶癌(invasive lobular carcinoma,ILC)组织中Ki-67表达的研究较少,对其预后预测价值尚需进一步文献支持.本研究探讨ILC组织不同临床病理特征下Ki-67表达差异及其与预后的关系.方法 收集天津医科大学肿瘤医院2003-01-10-2012-12-15收治的381例乳腺ILC患者的临床病理资料,分析Ki-67与其临床病理特征的相关性.分析不同年龄、月经状态、体质量指数、家族史、肿瘤大小、淋巴结状态、病理学分期、组织学分型、ER状态、PR状态、HER-2状态和p53状态下,Ki-67表达与预后的关系.结果 381例ILC组织中Ki-67低表达76例(19.9%),中表达91例(23.9%),高表达214例(56.2%).在不同肿物大小(χ2=12.524,P=0.014)、腋窝淋巴结情况(χ2=6.114,P=0.047)、临床分期(χ2=10.434,P=0.034)、ER表达(χ2=6.339,P=0.041)和组织学类型(χ2=78.288,P<0.001)情况下,Ki-67表达差异有统计学意义.Ki-67表达与肿物大小(r=0.168,P=0.001)、腋窝淋巴结情况(r=0.108,P=0.036)、临床分期(r=0.149,P=0.004)和组织学类型(r=0.532,P<0.001)呈正相关.Ki-67表达与ER表达呈负相关,r=-0.112,P=0.029.在肿瘤大小2~5 cm、有腋窝淋巴结转移及临床Ⅱ期ILC组织中,Ki-67表达对患者总生存(overall survival,OS)差异有统计学意义,P<0.05;而对无病生存(disease-free survival,DFS)差异无统计学意义,P>0.05.Cox多因素分析显示,有无淋巴结转移(P=0.000)是ILC总生存的独立预后因素,而肿瘤大小、临床分期和Ki-67表达水平不是影响ILC总生存的独立预后因素,P>0.05.结论 乳腺ILC组织中Ki-67高表达.就诊时肿物越大、有腋窝淋巴结转移和临床分期越高,Ki-67表达水平越高,而ER表达水平越高,Ki-67表达水平越低,肿物大小2~5 cm、有腋窝淋巴结转移及临床Ⅱ期,即中低度恶性ILC组织中Ki-67表达对患者预后有一定的预测价值,但不是独立预后因素,Ki-67对ILC预后预测作用尚需进一步研究.     

Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies

The vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been shown to play major roles not only in physiological but also in most pathological angiogenesis, such as cancer. VEGF belongs to the PDGF supergene family characterized by 8 conserved cysteines and functions as a homodimer structure. VEGF-A regulates angiogenesis and vascular permeability by activating 2 receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk1 in mice). On the other hand, VEGF-C/VEGF-D and their receptor, VEGFR-3 (Flt-4), mainly regulate lymphangiogenesis. The VEGF family includes other interesting variants, one of which is the virally encoded VEGF-E and another is specifically expressed in the venom of the habu snake (Trimeresurus flavoviridis). VEGFRs are distantly related to the PDGFR family; however, they are unique with respect to their structure and signaling system. Unlike members of the PDGFR family that strongly stimulate the PI3K-Akt pathway toward cell proliferation, VEGFR-2, the major signal transducer for angiogenesis, preferentially utilizes the PLCγ-PKC-MAPK pathway for signaling. The VEGF-VEGFR system is an important target for anti-angiogenic therapy in cancer and is also an attractive system for pro-angiogenic therapy in the treatment of neuronal degeneration and ischemic diseases.     

Ki-67和 AR 在三阴性乳腺癌中的表达及与复发的关系

目的：探讨增殖细胞抗原（Ki-67）和雄激素受体（AR）在三阴性乳腺癌（TNBC）的表达及其与术后复发之间的关系。方法回顾性分析中山大学附属江门医院2006年1月至2010年12月66例TNBC 和215例非三阴性乳腺癌（NTNBC）病理标本,采用免疫组织化学法检测 Ki-67和 AR 在其组织中的表达情况,并通过随访分析 TNBC 复发与 Ki-67和 AR 表达之间的关系,结果采用 SPSS 19．0进行统计分析。结果 TNBC 组织中 Ki-67阳性率为75．76％（50／66）,明显高于其在 NTNBC 组织中的阳性率62．33％（134／215,χ2＝4．031,P ＝0．045）;TNBC 组织中 AR 阳性率为31．82％（21／66）,明显低于其在NTNBC 组织中的阳性率76．28％（164／215,χ2＝44．382,P ＜0．001）。TNBC 组织中 Ki-67的表达与组织学分级（χ2＝6．031,P ＝0．049）、肿瘤直径（χ2＝6．630,P ＝0．036）、淋巴节状态（χ2＝5．440,P ＝0．020）有关;AR 的表达与绝经状态（χ2＝5．341,P ＝0．021）、体重指数（χ2＝4．369,P ＝0．037）相关。TNBC 术后复发与 Ki-67的表达有关（χ2＝4．125,P ＝0．042）,与 AR 表达无关（χ2＝1．257,P ＝0．262）。结论 Ki-67的高表达和 AR 的低表达在TNBC中具有明显特征,Ki-67阳性患者更易复发,可作为预测 TNBC 术后复发的指标。     

乳腺癌组织中乳腺癌易感基因1、增殖细胞核抗原Ki-67表达的临床意义

目的 探讨乳腺癌组织中乳腺癌易感基因1（BRCA1）、增殖细胞核抗原Ki-67表达的临床意义.方法 采用免疫组织化学法检测194例乳腺癌病理组织标本BRCA1、Ki-67的表达情况,并对其与临床病理参数的相关性进行分析.结果 194例乳腺癌中,淋巴结阳性组、雌激素受体（ER）/孕激素受体（PR）阴性组和人表皮生长因子受体2（HER-2）阳性组的BRCA1低表达率较高（P＜0.05）,三阴组中BRCA1低表达率高于非三阴组（P＜0.05）;Ki-67高表达者多为组织分级较高、ER/PR阴性和HER-2阳性患者（P＜0.05）;且BRCA1和Ki-67具有负相关性（P＜0.05）,绝经后、组织分级低、淋巴结阳性、ER/PR阴性、HER-2阳性患者的BRCA1低表达合并Ki-67高表达所占比例较高（P＜0.05）,但在三阴组与非三阴组间差异无统计学意义.结论 联合检测BRCA1、Ki-67对乳腺癌的临床转归具有一定预测意义,尤其是BRCA1可作为三阴性乳腺癌的预后因素之一.