AR在不同ER状态乳腺癌中的表达及临床病理意义

  目的  探讨雄激素受体（AR）在不同雌激素受体（ER）状态乳腺癌中的表达与临床病理特征间的关系及预后。  方法  从乳腺浸润性导管癌ER阳性和阴性病例中分别随机选取111例（ER+组）与113例（ER-组）,共计224例。采用免疫组化方法检测AR、ER、PR、HER-2、Ki-67、P53表达,对不同ER状态乳腺癌中AR表达与临床病理资料及预后因素进行分析。  结果  AR在浸润性导管癌中的阳性表达率为67.9%（152/224）,ER+组和ER-组分别为80.2%（89/111）、55.8%（63/113）。ER+组中AR的表达与肿瘤大小、组织学分级、pTNM分期和有无淋巴结转移相关（P < 0.05）;在ER-组中AR的表达与组织学分级、HER-2表达、绝经状态相关（P < 0.05）。单因素生存分析显示在ER+组和ER-组AR阳性者均具有较好的预后（P < 0.001,P=0.046）,Cox多因素回归分析显示在ER+组AR表达可作为影响无瘤生存的独立因素。  结论  AR可以作为指导临床内分泌治疗新的靶标,为不同ER状态乳腺癌激素治疗提供依据。      

雄激素受体在不同分子亚型乳腺癌中的表达及其意义

目的探讨乳腺癌组织雄激素受体（androgen receptor,AR）的表达,分析其在各分子亚型中表达的特点及其意义。方法采用免疫组织化学方法检测AR在335例乳腺浸润性导管癌石蜡包埋组织中的表达,结合66月随访情况,分析AR在五个分子亚型中表达的特点。 结果乳腺癌组织中AR阳性率较高,达72.5%,尤其在ER阴性PR阴性乳腺癌病例,AR常常显示阳性（占53.2%）。较多 (61.0%) basal like型乳腺癌AR显示阴性,提示预后欠佳。在luminal A、luminal B、basal-like以及normal-like亚型中AR阳性组出现局部复发、远处转移或死亡比例较AR阴性组少(P=0.019,0.044,0.034和 0.032),生存曲线也显示了AR阳性患者预后较好(P=0.006,0.013,0.036和0.010)。结论检测乳腺癌AR的表达水平有助于改进和细化乳腺癌的分子分型,为指导个体化治疗提供理论依据。     

空泡膜蛋白1及其与肿瘤关系的研究进展

0 引言 空泡膜蛋白Ⅰ (vacuole membrane protein 1,Vmp1)[1]是近年来发现的一个跨膜蛋白.研究发现Vmp1为蛋白分泌、细胞器形成及多细胞发育过程所必需,在人体许多肿瘤组织中如乳腺癌、肾癌、肝癌等均有表达,且在原发与转移性肿瘤中表达不一致,被预测其可能是一个肿瘤相关蛋白.现概要介绍Vmp1的发现、结构特点、生物学功能,并着重综述Vmp1与肿瘤之间的关系及相关机制的研究进展. 1 Vmp1的介绍 1.1 Vmp1的发现与结构 Vmp1为Dusetti等[1]于2002年在小鼠体内首次发现的一种与急性胰腺炎有关的蛋白质,通过在GenBank数据库中的比对,发现Vmp1和果蝇、新杆状线虫、拟南芥属等的氨基酸序列具有高度同源性,在不同物种中具有序列保守性,提示Vmp1可能具有重要的功能.     

Nek2剪接异构体及其与肿瘤关系的研究进展

Nek(NIMA-related kinase,Nek)激酶为哺乳动物细胞中的NIMA相关激酶。NIMA最初是在曲霉中被发现的,其对细胞周期突变体nimA进入有丝分裂起重要作用,过表达的NIMA甚至能使处于细胞周期中任意时刻的细胞进入有丝分裂[1]。     

分泌型乳腺癌的临床病理特征

目的：探讨乳腺分泌型癌的临床病理特征、诊断和鉴别诊断要点。方法 ：分析14例分泌型乳腺癌患者的临床病理资料,进行光镜观察,部分病例进行组织化学及免疫组化染色,并复习文献。结果：分泌型乳腺癌临床及病理大体观察与其他类型乳腺癌无明显区别,主要表现为乳房内肿块,多位于乳晕区,大体观察肿物大多连界不清、质地硬,光镜下肿瘤细胞主要排列成实性、小囊性和导管性三种结构,瘤细胞有颗粒性嗜酸性胞质,瘤细胞内外有大量均质嗜伊红PAS阳性分泌物。腋下淋巴结转移较少（2/14）。无局部复发或远处转移（随访3～14年）。结论：分泌型乳腺癌为罕见且预后较好的乳腺癌,确诊必须依靠病理检查。     

The prognosis significance of cathepsin-d expression in the different locations in axillary nodes negative carcinoma

Cathepsin-D (Cath-D) is an aspartyl lysosomal protease expressed in all kinds of tissue[1] and has been shown to be an important marker of poor prognosis[2] in the past few years. It stimulates the growth of the tumor cells and the degradation of the basement membranes and extracellular matrix, thus promoting cancer cells to invade the regional tissues and metastasize to distant sites.[3] In previous reports, the prognostic value of Cath-D for breast cancer patients remains controversial.[4,…     

副乳腺大导管乳头状瘤1例

副乳腺大导管乳头状瘤甚为罕见,本文报告1例。患者女,37岁,已婚,足月产1胎,月经正常。因右腋窝肿块2月于1992年10月8日入院。查体:双乳呈下垂型,未触及肿块,右腋前隆起5×4×3cm,未见乳头及乳晕,其内可触及肿块约3×3×2cm,边界不清,柔韧感。左腋部正常。双乳X线软片未见异常。临床诊断右副乳腺腺体增生。行肿物切除术。巨检:标本为4×4×3cm,切面周围为脂肪组织,中央为乳腺腺体,并有牙膏样分泌物从导管内溢出。镜检:乳腺组织中有3～4个扩张的大导管,其中一个大导管内有一单发的乳头状瘤,大小为0.3×0.2     

Expressions and significances of Nek2 and β-catenin in breast invasive ductal carcinoma

Objective To investigate the expression and significance of NIMA related kinases 2 ( Nek2) and β-catenin (β-cat) in breast invasive ductal carcinoma (IDC) and concomitant ductal carcinoma in situ (DCIS). The roles of Nek2 and β-acat in the development and progression of breast cancer were explored. Methods The protein expression of Nek2 and β-cat in the tissues from 186 patients with IDC, 75 concomitant DCIS, 80 normal tissue adjacent to carcinoma and 40 fibroadenoma of breast was detected by using immunohistochemistry. Their relationship between clinicopathologic parameters was analyzed. Results There were correlations between the Nek2 expression in cytoplasm and grade(x2=8. 756;P<0.05) as well as tumor size (x2=6. 518;P<0.05) in IDC. The positive expression of Nek2 in nuclei was 32/186 and 15/75 in IDC and DCIS, respectively. There were correlations between the β-cat expression on the cytomembrane and grade (x2=45.493;P<0. 01) , TNM stage (x2=9. 510;P<0. 01), node status (Z=-2.035;P<0. 05) and estrogen receptor (ER) status (Z=-3. 004;P<0. 01). The β-cat expression on the cytoplasm was related with TNM stage (x2=8. 194;P<0. 05). The expression of Nek2 and β-cat had no correlation with clinicopathologic parameters in concomitant DCIS (P>0. 05), the Nek2 expression in cytoplasm had a correlation with the β-cat expression in cytoplasm (r=0. 226,P<0.05) in concomitant DCIS, and the same relationship could also be seen in IDC (r=0. 368,P<0.01). There was significant difference in the β-cat expression on the cytomembrane between IDC and concomitant DCIS (Z=-3. 804,P<0. 01). In the normal tissue adjacent to carcinoma and fibroadenoma, the Nek2 expression in cytoplasm and nuclei Was low or negative;the β-cat expression on the cytomembrane was high but that Was low in cytoplasm.Conclusion Centrosome regulatory factor Nek2 and β-cat can support a new way to explore the mechanisms of breast tumorigrenesis.And they may become a new antitumor drug target in the future.     

雄激素受体在乳腺癌细胞中的表达及其对细胞增殖的影响

Objective To evaluate the expression of androgen receptor (AR) in the breast cancer cell lines and its effect on proliferation of breast cancer cells. Methods The estrogen receptor (ER) -positive MCF-7 and ER-negative MDA-MB-453 cells were involved in this study and cultured in vitro. The expression of AR was detected by using Western blotting. Cell proliferation was determined by methyl thiazol tetrazolium (MTT) assay after the treatment with different concentrations of dihydrotestosterone (DHT) ( 1 x 10 -7, 1 x 10- 8, 1 x 10 -9 mol/L) for 48, 96 and 144 h respectively. Cell cycle was analyzed by flow cytometry following culture for 72 h. Results DHT increased the AR expression in the two breast cancer cell lines. AR pathway could inhibit proliferation of MCF-7 and MDA-MB-453 cells. There was no significant difference in absorbance values among three treatment groups at different time points (P ＞ 0. 05). Cell cycle analysis revealed that the proportion of cells at G1 phase was increased, and that at S phase decreased. Conclusion AR pathway may inhibit proliferation of ER-negative MDA-MB-453 breast cells as well as ER-positive MCF-7 cells, by suppressing the process of G1 to S phase progression.     

乳腺乳头状瘤病和导管原位癌cyclinD1、p16和Ki-67表达

目的　探讨细胞周期调控因子cyclinD1、p16和Ki 6 7与乳腺乳头状瘤病及导管内癌的相关性及其临床病理意义。方法　通过免疫组化S P法检测轻度乳头状瘤病、重度乳头状瘤病和导管内癌各 4 0例中cyclinD1、p16和Ki 6 7的蛋白表达情况 ,并用 2 0例正常乳腺组织作对照。结果　cyclinD1在轻度、重度乳头状瘤病和导管内癌组中阳性率分别为 2 7 5 %、5 0 0 %、6 0 0 % ,3组间差异有显著性 (χ2 =8 92 9,P <0 0 5 )。p16蛋白表达分别为 80 0 %、5 2 5 %、4 0 0 % ,3组间差异均有显著性 (χ2 =8 6 87,P <0 0 1)。轻度与重度乳头状瘤病组比较均有差异 ,但重度乳头状瘤病与导管内癌组间差异无显著性。Ki 6 7阳性率在 3组间差异有显著性 ,组间两两比较也分别有统计学差异。在各组中 ,Ki 6 7与cyclinD1呈正相关 ,与 p16呈负相关 ,cyclinD1与 p16呈负相关。结论　cyclinD1、p16和Ki 6 7表达异常在乳腺癌发生、发展演进过程中是一种早期事件。重度乳头状瘤病是重要的癌前病变。调节cyclinD1和 p16的平衡可能是癌前病变基因治疗的一条途径