BcL—2和Bax表达在乳腺浸润性导管癌细胞凋亡中的作用

目的：探讨Bcl—2和Bax表达在乳腺浸润性导管癌细胞凋亡过程中的作用。方法：用免疫组织化学方法检测18例乳腺浸润性导管癌及癌旁组织中Bcl—2和Bax的表达，用TUNEL法检测乳腺组织中细胞凋亡。结果：乳腺浸润性导管癌与癌旁组织比较，凋亡细胞明显减少，癌组织及癌旁组织中Bcl—2的阳性表达分别为15／18和6／18，差异有极显著性(P＜0．01)；Bax的阳性表达分别为8／18和14／18，差异有显著性(P＜0．05)。结论：Bcl—2和Bax在乳腺浸润性导管癌的细胞凋亡调控中有重要作用。     

乳腺浸润性导管癌组织Livin和Caspase-3蛋白表达及其相关性研究

目的:探讨细胞凋亡相关因子Livin和Caspase-3在乳腺浸润性导管癌组织中的表达及相关性.方法:应用免疫组织化学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(距癌组织≥4 cm,组织学结构正常)标本中Livin、Caspase-3的表达情况,探讨两者的相关性及其与临床病理因素的关系.结果:Livin蛋白在癌组织中的阳性表达率为64.3％,高于乳腺增生和乳腺癌旁组织的25.0％和10.0％( P＜0.05);Caspase-3蛋白在癌组织中的阳性表达率为45.7％,明显低于乳腺增生和乳腺癌旁组织中的75.0％和80.0％(P＜0.05);Livin蛋白与Caspase-3蛋白表达呈负相关,P＜0.05.Livin蛋白的阳性表达率随着临床分期增加显著升高(P＜0.05),但与患者年龄、肿瘤大小、组织学分级、淋巴结转移无关,P＞0.05.Caspase-3蛋白的表达随着临床分期的增加其阳性表达率下降(P＜0.05),与患者年龄、肿瘤大小、组织学分级和淋巴结转移无关,P＞0.05.在乳腺浸润性导管癌组织中Livin蛋白与ER、PR表达负相关(P＜0.05),与c-erbB-2的表达无相关性,P＞ 0.05.Caspase-3蛋白与ER、PR表达显著正相关(P＜0.05),与c-erbB-2表达无相关性,P＞0.05.结论:Livin在乳腺癌的发生发展中发挥重要促进作用,可能成为乳腺浸润性导管癌诊断中的标志,并有望成为乳腺癌治疗的新靶点.Caspase-3在Livin抗凋亡通路中发挥着重要作用.     

簇集蛋白在乳腺浸润性导管癌中的表达及临床意义

 目的　探讨细胞凋亡抑制因子簇集蛋白在乳腺浸润性导管癌组织中的表达及临床意义。方法　应用免疫组织化学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（距癌组织≥4 cm,组织学结构正常）标本中簇集蛋白的表达情况,并探讨其与乳腺癌各临床病理学参数间的关系。结果　簇集蛋白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 %（4／20）及71.4 ％（50／70）,乳腺浸润性导管癌组织中的簇集蛋白表达水平明显高于乳腺增生（χ2＝17.143,P＜0.05）及乳腺癌旁正常组织（χ2＝19.048,P＜0.05）;簇集蛋白在乳腺浸润性导管癌中的表达随着临床分期的增加阳性表达率显著升高（χ2＝4.667,P＜0.05）且与组织学分级（χ2＝5.233,P＜0.05）及淋巴结转移情况（χ2＝4.667,P＜0.05）有关,与患者年龄、肿瘤大小及组织学类型无关（χ2值分别为0.024、0.406、0.091,均P＞0.05）。在乳腺浸润性导管癌组织中簇集蛋白与ER、PR的表达负相关（r值分别为-0.362、-0.290,均P＜0.05）,与C-erbB-2的表达无相关性（r＝0.129,P＞0.05）。结论　簇集蛋白可能通过抑制细胞凋亡在乳腺癌的发生、发展中发挥重要促进作用,可能成为乳腺浸润性导管癌诊断中的标志物,并有望成为乳腺癌治疗的新靶点。     

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。     

Bcl-2,Bax在乳腺癌中表达的临床意义

目的　探讨Bcl 2 ,Bax在乳腺癌中表达的临床意义。方法　免疫组化链霉菌素 生物素 (S P)法对术前未使用过化疗、放疗及免疫治疗的乳腺癌 82例 (其中有腋窝淋巴结转移的 61例 ) ,15例乳腺良性肿瘤和 15例正常乳腺组织作对照 ,检测Bcl 2 ,Bax的表达情况。结果　Bcl 2在癌组织中的表达 ( 5 6 10 % )与正常乳腺组织 ( 3 3 3 3 % )和良性肿瘤 ( 4 0 0 0 % )中的表达无统计学差异 ,在不同种类、不同分级的浸润性导管癌中无明显差异 (P >0 0 5 ) ,在有转移 ( 4 7 5 4% )和无转移组 ( 80 95 % )中有明显差异 (P <0 0 1)。Bax在癌组织中的 ( 60 98% )表达与正常乳腺组织 ( 73 3 3 % )和良性肿瘤中 ( 60 0 0 % )的表达无统计学差异 ,在不同种类癌中无明显差异 (P>0 0 5 ) ,在不同分级的浸润性导管癌中有显著差异 (P <0 0 5 ) ,在有转移 ( 67 2 1% )和无转移组 ( 4 2 86% )中有显著差异 (P <0 0 5 )。两者在乳腺癌中的表达有相关 (P <0 0 5 )。结论　检测乳腺癌Bcl 2 ,Bax基因的表达情况 ,有助于预测乳腺癌患者的淋巴结转移情况及预后     

Survivin在乳腺腺病、乳腺管状腺瘤、乳腺癌组织中的表达差异及其意义

目的检测Survivin（SVV）蛋白在乳腺腺病、乳腺管状腺瘤、乳腺癌组织（乳腺导管内癌、浸润性乳腺导管癌）和乳腺癌细胞系细胞中的表达,及浸润性乳腺导管癌中SVV的表达与肿瘤大小,Her-2、ER、PR、p53、及ki-67蛋白表达及细胞凋亡情况的相关性,研究SVV在乳腺良性病变和良恶性肿瘤中的表达情况对鉴别诊断及乳腺癌预后的意义。方法选择乳腺腺病、乳腺管状腺瘤各20例、乳腺导管内癌、乳腺浸润性导管癌各30例,5个乳腺癌细胞系。免疫组化方法检测SVV、Her-2、ER、PR、053、及ki-67在组织和细胞系的表达情况;应用TUNEL原位凋亡检测细胞的凋亡。结果SVV在乳腺腺病、乳腺管状腺瘤、乳腺导管内癌和浸润性乳腺导管癌组织的表达比例分别为7／20、6／20、20／30和24／30;其相应的高表达比例为3／20、1／20、14／30及16／30。与乳腺腺病、乳腺管状腺瘤组织相比,SVV在乳腺癌组织的表达具有明显增强（P〈0．05）。在浸润性乳腺导管癌组织中,SVV的表达与肿瘤大小、淋巴结转移、细胞凋亡以及Her-2、ER、PR、p53、及ki-67的表达无明显的相关性（P〉0．05）。结论SVV在乳腺导管内癌及乳腺浸润性导管癌组织中的表达明显增强,对乳腺腺病、乳腺管状腺瘤与乳腺癌的鉴别具有一定临床意义。     

RhoA和Ezrin在乳腺浸润性导管癌中的表达及其临床意义

目的： 探讨RhoA和Ezrin在乳腺浸润性导管癌中的表达及其临床意义。 方法： 选用2008年1月至12月河北医科大学第四医院收治的乳腺浸润性导管癌患者术后石蜡标本86例。免疫组织化学染色检测肿瘤组织中RhoA和Ezrin的表达情况,分析其临床病理意义及两者的相关性。 结果： 86例乳腺浸润性导管癌组织中,RhoA的阳性表达率为60.47%,显著高于乳腺正常导管上皮组织的20%（P<0.05）;Ezrin的强阳性表达率为65.12%,显著高于乳腺正常导管上皮组织（P<005）。乳腺浸润性导管癌组织中RhoA的阳性表达和Ezrin的强阳性表达与患者年龄无关（P>0.05）,与腋淋巴结转移、组织学分级和TNM分期有关（均P<005）。乳腺浸润性导管癌组织中RhoA的阳性表达和Ezrin的强阳性表达呈正相关（P<001）。 结论： 乳腺浸润性导管癌高表达RhoA和Ezrin,并在导管癌的发生、发展过程中发挥作用。     

DNA修复基因hrad51在乳腺良、恶性病变中的表达及其生物学意义

目的　初步探讨 DNA修复基因 hrad5 1在乳腺组织病变和乳腺癌发生中的生物学意义。方法　应用S- P免疫组化法 ,分别检测了 hrad5 1蛋白在乳腺纤维腺瘤、乳腺导管上皮不典型增生、乳腺癌癌旁正常组织及乳腺癌中的表达情况。结果　 (1) hrad5 1蛋白在乳腺纤维腺瘤、导管上皮不典型增生、乳腺癌癌旁正常组织及乳腺癌中的表达率分别为 4 .0 %、13.6 %和 10 .0 %和 39.2 % ;(2 )乳腺癌中 hrad5 1蛋白的高表达与肿瘤组织分级之间 (P=0 .0 0 0 )、TNM分期之间 (P=0 .0 2 6 )呈正相关 ,与 ER的阳性表达之间 (P=0 .0 35 )呈负相关。结论　 (1) hrad5 1蛋白在不同病变乳腺组织中呈现不同表达 ,在乳腺癌组织中存在高度表达 ;(2 )检测 hrad5 1蛋白的表达情况可望成为评价乳腺癌患者预后的一个新指标     

乳腺癌组织人端粒酶逆转录酶表达及其临床病理意义

目的:分析乳腺浸润性导管癌中人端粒酶逆转录酶(hTERT)的蛋白表达与肿瘤的临床分期、组织学分级、转移及患者预后的关系。方法:采用免疫组化SLAB法,检测67例乳腺浸润性导管癌石蜡包埋组织中hTERT的蛋白表达。结果:67例乳腺浸润性导管癌中强阳性者44例,弱阳性者23例。hTERT蛋白主要定位于癌细胞胞质,少部分细胞核也有表达。本组乳腺癌分期和分级越高,hTERT蛋白表达的强阳性率越高,P值分别为0.002 8和0.010 2。hTERT强阳性组转移率为63.6%(28/44),弱阳性组转移率为30.4%(7/23),两者差异有统计学意义,P=0.000 0。hTERT强阳性组3年生存率为69.2%(27/39),hTERT弱阳性组3年生存率为95.7%(22/23),两者差异有统计学意义,P=0.000 0。结论:hTERT的蛋白表达可能与乳腺浸润性导管癌的分化和转移有关,可以作为判断乳腺癌患者预后的指标之一。     

HIF-1α和BCRP在乳腺浸润性导管癌组织中的表达及临床意义

目的 探讨低氧诱导因子-1α（HIF-1α）和乳腺癌耐药蛋白（breast cancer resistance protein,BCRP）在乳腺浸润性导管癌组织中的表达及临床意义。方法 采用免疫组化SP法分别检测75例乳腺浸润性导管癌组织和15例癌旁组织中HIF-1α和BCRP的表达水平。结果 HIF-1α和BCRP在乳腺浸润性导管癌癌组织的阳性表达率分别为61.3%和41.3%,显著高于癌旁组织的阳性表达率（均为0）,两组比较差异均有统计学意义（P均〈0.05）;两者的表达均与肿瘤组织学分级、临床分期及淋巴结转移相关（P均〈0.05）,而与患者年龄、肿瘤大小无关（P均〉0.05）。在乳腺浸润性导管癌组织中HIF-1α和BCRP的表达呈正相关（r=0.333,P〈0.004）。结论 HIF-1α和BCRP的表达在乳腺浸润性导管癌的发生、发展中可能起一定作用。     

Expression of HIF-1α in breast cancer and precancerous lesions and the relationship to clinicopathological features简

Objective： The aim of this study was to observe the expressions and clinical significance of HIF-1a in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： We analyzed the HIF-1a expression in 128 cases of invasive ductal carcinomas, 146 precancerous lesions patients including 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia. 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The specimens were evaluated for HIF-1a, estrogen receptor （ER） ＆ progesterone receptor （PR）, epidermal growth factor receptor type 2 （HER2/neu） and Ki-67. Immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40 x magnification and recorded as the percentage of positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized. The express of HIF-1a and their relationship with multiple biological parameters including ER ＆ PR, HER2/neu and Ki-67, the biomarkers levels of CA153, CA125 TSGF, and CEA in blood serum and nipple discharge, histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： Compared with usual ductal hyperplasia, the positive expression rate of HIF-1a in atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinomas group was significantly increased （P 〈 0.01）. The positive rates of HIF-1a in invasive ductal carcinomas were 68.75%, which were significantly higher than that in ductal carcinoma in situ （43.8%）, atypical ductal hyperplasia （31.6%）, usual ductal hyperplasia （9.4%; X2 = 13.44, 22.27, 52.79, respectively, P 〈 0.01）. Statistical analysis showed that difference of abnormal expression rate of HIF-1a between ductal carcinoma in situ and usual ductal hyperplasia （X2 = 18.37, P = 0.00）, atypical ductal hyperplasia and usual ductal hyperplasia （x2 = 8.14, P = 0.00） was significant （P = 0.00）. However, no significant difference in the positive expression rate of HIF-1a was found between atypical ductal hyperplasia and ductal carcinoma in situ tissue （X2 = 2.19, P = 0.14）. There was a significantly difference in the mean HIF-1a frequency between ER ＆ PR positive invasive ductal carcinomas group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was not difference in the mean HIF-1a between age （〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm; P 〉 0.05）. The nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in invasive ductal carcinomas HIF-1a positive patients were significantly higher than those in the negative patients （P 〈 0.05）. Conclusion： In breast cancer, HIF-1a expressibn was abnormally increased. The aberration of HIF-1a may play a key role during oncogenesis （atypical ductal hyperplasia or ductal carcinoma in situ） and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. The abnormal expression of HIF-1a may be as an early event in the development of breast tumor. The over-expression of HIF-1a might be important biological markers for invasion, metastasis and recurrence of breast cancer.     

乳腺浸润性导管癌患者手术前后血浆VEGF的变化及其意义

目的了解乳腺浸润性导管癌患者手术前后血浆血管内皮生长因子(P VEGF)的变化情况及其可能的意义。方法采用酶联免疫吸附试验方法(ELISA)检测39例乳腺浸润性导管癌患者手术前后的P VEGF含量,检测22例乳房良性疾病和18例健康对照的P VEGF,并进行比较分析。结果乳腺浸润性导管癌患者P VEGF水平明显高于乳房良性疾病患者(P=0.000),和健康对照组P=0.000。乳房良性疾病与健康对照组比较差异无统计学意义,P=0.063。手术后7d左右的P VEGF与手术前及良性疾病比较差异均无统计学意义,P值分别为0.816和0.071,但高于健康对照组,P=0.000。手术后30d左右P VEGF明显低于手术前水平,P=0.000;且与良性疾病和健康对照组比较差异无统计学意义,P值分别为0.243和0.582。结论乳腺浸润性导管癌的肿瘤细胞产生大量VEGF,P VEGF有可能成为乳腺浸润性导管癌的一个监测指标。     

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.     

乳腺导管内乳头状瘤和导管癌中Pten、p16基因蛋白表达研究

 目的　分析抑癌基因Pten及p16蛋白在乳腺导管内乳头状瘤和导管癌组织中的表达 ,以进一步探讨导管内乳头状瘤的生物学特性。方法　应用间接免疫荧光染色流式细胞术对 2 3例乳腺导管内乳头状瘤、2 9例导管癌Pten及p16在蛋白水平上的表达情况进行定量检测。结果　正常乳腺组织、导管内乳头状瘤和导管癌组织中Pten蛋白表达阳性率逐渐下降 ,分别为 10 0 %、4 7.83%及 10 .34% ,三组比较有显著性差异 (P <0 .0 1)。与Pten结果相似 ,在所有的正常乳腺组织中 p16均呈阳性表达 ,而在导管内乳头状瘤和导管癌中p16的表达均有不同程度降低 ,分别为 82 .6 1%及 2 4 .14 % ,两组与正常对照比较有显著性差异 (P <0 .0 1) ,而导管内乳头状瘤与导管癌之间 p16蛋白表达无统计学意义 (P >0 .0 5 )。结论　乳腺导管内乳头状瘤存在Pten和p16蛋白表达异常 ,提示导管内乳头状瘤是一种具有抑癌基因变化的癌前病变。     

Maspin和MMP-2在乳腺浸润性导管癌中的表达及其临床意义

目的探讨Maspin和MMP-2在乳腺浸润性导管癌组织中的表达及意义。方法应用免疫组织化学SP法检测60例乳腺浸润性导管癌及20例正常乳腺组织中Maspin和MMP-2的表达。结果Maspin在乳腺浸润性导管癌中表达阳性率为45.0%,低于在正常乳腺组织中的表达阳性率95.0%(P<0.05);MMP-2在乳腺浸润性导管癌中表达阳性率为75.0%,高于在正常乳腺组织中的表达阳性率15.0%(P<0.05)。Maspin和MMP-2的表达均与乳腺浸润性导管癌的淋巴结转移相关(P<0.05),MMP-2的表达还与乳腺浸润性导管癌临床分期相关(P<0.05)。乳腺浸润性导管癌中Maspin与MMP-2的表达呈负相关(r=-0.11,P<0.05)。结论 Maspin对乳腺浸润性导管癌的转移有抑制作用,MMP-2对乳腺浸润性导管癌的转移有促进作用,检测Maspin和MMP-2的表达可以成为判断乳腺浸润性导管癌浸润及转移能力的重要指标之一。     

KLF4和KLF5在乳腺浸润性导管癌中的表达及意义

目的 探讨转录因子Kruppel 样因子（KLF）4和KLF5在乳腺浸润性导管癌中的表达,分析其表达与乳腺浸润性导管癌的发生、发展及临床病理因素之间的关系。方法 采用免疫组化SP法检测30例乳腺浸润性导管癌组织及10例对应癌旁正常组织中KLF4和KLF5蛋白的表达,分析其表达与乳腺癌临床病理特征的关系。结果 KLF4和KLF5均主要表达于细胞核。乳腺浸润性导管癌组织中KLF4低表达,阳性表达率为6.7％,低于癌旁正常乳腺组织（70.0%）,差异有统计学意义（P＜0.05）;KLF5在乳腺癌组织中高表达,阳性表达率为90.0％,高于癌旁正常乳腺组织（30.0%）,差异有统计学意义（P＜0.05）。乳腺浸润性导管癌组织中KLF4和KLF5的表达与年龄、绝经情况、组织学分级、淋巴结转移、ER及PR表达无关（P＞0.05）,而KLF5与HER-2表达水平有关（P＜0.05）。KLF4和KLF5在乳腺浸润性导管癌中的表达无相关性（r=-0.356,P=0.053）。结论 KLF4和KLF5表达与乳腺浸润性导管癌的发生密切相关,可以作为预测乳腺浸润性导管癌发生、发展及转移的评价指标之一。     

Galectin-3及p-AKT在乳腺浸润性导管癌的表达及意义

目的研究Galectin-3和p-AKT在乳腺浸润性导管癌（IDC）中的表达及意义。方法应用免疫组织化学Envision二步法检测97例乳腺IDC和20例乳腺腺病组织中Galectin-3和p-AKT蛋白的表达情况。结果 Galectin-3和p-AKT表达在乳腺IDC（阳性率分别为84.5%、77.3%）和良性病变中（阳性率分别为25.0%、30.0%）差异具有统计学意义（P〈0.05）;在乳腺IDC中,死亡组Galectin-3和p-AKT表达（97.1%、91.4%）明显高于生存组（77.4%、69.4%）（P〈0.01）,p-AKT表达与淋巴结转移相关（P〈0.01）,Galectin-3和p-AKT表达与乳腺IDCTNM分期、组织学分级无关,与年龄相关;Galectin-3表达和p-AKT表达呈正相关（r=0.606,P〈0.05）。结论乳腺IDC中Galectin-3和p-AKT表达可能促进肿瘤演进,高表达Galectin-3和p-AKT的乳腺IDC具有更高侵袭性和淋巴结转移能力,并提示预后不佳。对Galectin-3和p-AKT作用机制的深入研究有可能使其成为乳腺IDC患者个体化治疗的新靶标。     

Expression of death-related genes and their relationship to loss of apoptosis in T1 ductal breast carcinomas

Expression of the death-related proteins (DRPs) Bcl-2, Bax, Bcl-x and Bak that regulate cell survival and death was examined using immuno-histochemical methods in a group of 142 T₁ (<2 cm) ductal breast carcinomas. Immunostaining results were correlated with loss of apoptosis and clinico-pathological parameters such as histological grade (HG) and lymph node involvement. Expression of anti-apoptotic proteins Bcl-2 and Bcl-x was found in 57.0% and 62.75% of tumors, respectively. Bcl-2 expression, but not Bcl-x expression, was related to loss of apoptosis. Expression of the apoptotic proteins Bax and Bak was present in 58% of Bcl-2-negative tumors and associated significantly with an increase in apoptosis. Expression of these DRPs was associated significantly with the HG of the tumors: Bcl-2 and Bak expression was predominant in HG I/II tumors, whereas expression of Bcl-x_L and Bax was commonly observed in HG III tumors, as occurs for p53 over-expression. Our results suggest that the loss or gain of apoptosis is regulated tightly in T₁ breast carcinomas through the expression of different effectors along with tumor cell differentiation. Int. J. Cancer (Pred. Oncol.) 79, 103–110, 1998.© 1998 Wiley-Liss, Inc.     

Expression and clinical significance of E-cadherin, β-catenin and E-cadherin-catenins complex in breast cancer and precancerous lesions简

Objective： The aim of our study was to observe the expressions and clinical Significance of E-cadherin, β-catenin and E-cadherin-catenins complex in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： Immunhistochemical UltraSensitiveTM S-P method was employed to detect the expression of E-cadherin, β-catenin and E-cadherin-catenins complex in 128 cases of invasive ductal carcinomas, 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia, 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The express of E-cadherin, β-catenin and their relationship with mult biological parameters including histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： （1） The staining patterns character of E-cadherin, β-catenin and E-cadherin-catenins complex： In UDH breast tissues, E-cadherin and a-catenin were expressed on cell membrane of ductal and acinic cells, showing cellular contour and border among cells. The abnormal expression of the three proteins occurred in breast invasive ductal carcinomas, ductal carcinoma in situ and atypical ductal hyperplasia tissues, showing cytoplasmic or nuclear staining, decrease and loss of cytomembrane staining. （2） The abnormal expression rates of E-cadherin, β-catenin and E-cadherin-catenins complex in invasive ductal carcinomas were 53.91%, 65.63% and 81.25%, which were significantly higher than that in ductal carcinoma in situ, atypical ductal hyperplasia, usual ductal hyperplasia tissues （P 〈 0.01）. Compared with usual ductal hyperplasia breast tissues group, the abnormal expression rates of E-cadherin, β-catenin and E-cadherin-catenins complex were significantly decreased （P 〈 0.01） in the breast cancer group. However, there was no significance of the abnormal expression rate between ductal carcinoma in situ and atypical ductal hyperplasia tissues groups （X2 = 0.76, P = 0.38; x2 = 0.14, P = 0.70; x2 = 0.81, P = 0.37; X2 = 2.19, P = 0.14） （P 〉 0.05）. （3） There was a significantly difference in the mean E-cadherin, β-catenin and E- cadherin-catenins complex frequency between estrogen receptor ＆ progesterone receptor positive IDC group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was no difference in the mean E-cadherin, β-catenin and E-cadherin-catenins complex frequency between age （_〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm） （P 〉 0.05）. Conclusion： In breast cancer, the expressions of E-cadherin, β-catenin and E-cadherin-catenins complex are abnormally decreased and are correlated with pathology grade, differentiation disturbance and metastasis. E- cadherin and β-catenin may be as the predictors for prognosis. Combined detection may improve accuracy and sensitivity of predicting metastasis and prognosis of breast Cancer.     

Expression of Bax and Bcl-2 in Tumour Cells and Blood Vessels of Breast Cancer and their Association with Angiogenesis and Hormonal Receptors

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expressionof Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated theassociation between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade,lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression.Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression ofBcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD(p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded thatthe number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumorcells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this wasinfluenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoralregion and angiogenesis was independent of anti-apoptotic activity.