脑膜瘤中GHR与SSTR1的表达及其意义

目的探讨生长激素受体(growth hormone receptor,GHR)和生长抑素受体1(somatostatin receptor 1,SSTR1)在脑膜瘤中的表达及其临床病理意义。方法采用免疫组化PV-6000法检测14例正常脑组织、107例脑膜瘤组织中GHR和SSTR1的免疫表达。结果 14例正常脑组织中有5例表达GHR、4例表达SSTR1,阳性率分别为35.7%、28.6%,107例脑膜瘤组织中有75例表达GHR,有70例表达SSTR1,阳性率分别为70.0%、65.4%。GHR、SSTR1在正常脑组织与脑膜瘤中的表达及在脑膜瘤不同的病理分型中的表达有差异(P<0.05);脑膜瘤组织中GHR与SSTR1的表达呈正相关性(P<0.01)。结论 GHR与SSTR1在脑膜瘤的发生、发展过程中发挥了一定的作用,为临床治疗提供理论依据。     

不同ER、PR状态乳腺癌中AR的表达及其意义

目的探讨AR在不同ER、PR状态乳腺癌中的表达及意义。方法采用免疫组化方法检测AR、ER、PR在173例乳腺癌中的表达,依据结果分组:(1)AR状态分组:AR阳性组和AR阴性组;(2)ER、PR状态分组:En组(ER、PR均阴性)、Ep组[ER和(或)PR阳性];(3)AR、ER、PR联合分组:En-AR+(En组且AR阳性)、En-AR-(En组且AR阴性)、Ep-AR+(Ep组且AR阳性)、Ep-AR-(Ep组且AR阴性),其中En-AR-又称为均阴性组,其他三组统称为部分或完全阳性组。不同分组方法比较与临床病理特征的关系。结果Ep组AR阳性率62.8%(54/86),En组AR阳性率37.9%(33/87),两组差异有显著性(P=0.001),AR阳性组体积小、核分裂少、组织学分级低(P0.05);En-AR-组表现为核分裂多、组织学分级高(P0.01),此外En组内AR阳性者核分裂少、组织学分级低(P0.05),Ep组内AR阳性者临床分期高(P=0.000),En-AR+、Ep-AR+、Ep-AR-比较均无差异。结论AR在不同激素状态乳腺癌中表达的意义不同,ER、PR均阴性乳腺癌表达AR者预后较好,ER、PR阳性乳腺癌表达AR者临床分期高。在选择针对性药物时应考虑到不同激素受体状态的组合。     

乳腺癌中AR及STC2的表达及其相关性分析

目的探讨AR、STC2在乳腺癌组织中的表达,分析两者与乳腺癌临床病理特征的相关性。方法选取77例乳腺癌组织,40例癌旁正常组织作为对照,采用免疫组化EnVision两步法分别检测AR和STC2的表达,采用χ~2检验分析两者与乳腺癌临床病理特征的关系。结果在乳腺癌组织中,AR阳性率为53.2%,STC2阳性率为64.9%,均高于癌旁正常组织,差异有统计学意义(P均0.001)。乳腺癌组织中AR和STC2在ER、PR状态及pTNM分期分组中表达差异有显著性(P0.05)。AR和STC2表达呈正性相关,且差异有统计学意义(r=0.432,P0.001)。结论 AR与STC2在乳腺癌中表达一致,且均呈高表达。     

肯尼迪病的研究进展

肯尼迪病（Kennedy disease ,KD ）,又称脊髓延髓肌萎缩症（spinal bulbar muscular atrophy ,SB‐MA）,是一种成年发病的X连锁隐性遗传性神经肌肉疾病。该病于1968年首先由 Kennedy 报告［1］。一般仅男性受累,发病率为1／5万［2］。该病进展较缓慢,主要累及脑干和脊髓下运动神经元,临床表现为肢体近端肌肉和延髓支配肌肉的萎缩、无力和束颤。可伴有不完全性雄激素不敏感综合征、感觉神经和内分泌系统受累及的临床表现［3］。基因分析是KD的诊断金标准。1991年 La Spada等［2］报告了该病的基因缺陷。其致病基因定位于Xq11‐12,是由于雄性激素受体（androgen receptor ,AR）基因1号外显子CAG序列重复突变所致。血清肌酸激酶增高、睾酮水平结果降低亦有助于 K D 的诊断［4］。其电生理改变也有很多特点。目前,已证实亮丙瑞林等药物能起到阻止或延缓KD动物模型病情进展的作用［5］,但KD的临床治疗研究尚处于起步阶段。早期诊断对评估预后很重要,临床对此病国内报道较少,尤其是无家族史的KD报道更少。由于对此病进行基因检测的阳性率较低,因此导致部分临床医生对该病的认识不足,本文对 KD的致病基因、发病机制、临床特征、辅助检查、诊断及治疗进展进行回顾及展望,以期加强各位临床医师对此病的进一步认识。     

DJ-1和mTOR表达在良性脑膜瘤复发中的意义

目的：探讨DJ-1和哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）在各类型脑膜瘤中的表达及其与良性脑膜瘤复发和演进的关系。方法：收集广东同江医院和中山大学附属第一医院行手术切除并随访的脑膜瘤病例72例,其中术后无复发的良性（WHO I级）脑膜瘤50例,术后复发良性脑膜瘤12例,高级别脑膜瘤（WHO II~III级）10例。采用免疫组织化学方法检测DJ-1和mTOR在脑膜瘤组织中的表达。结果：DJ-1和mTOR在术后无复发和术后复发的良性脑膜瘤及高级别的脑膜瘤中表达不同,DJ-1在3种脑膜瘤组织中的高表达分别为3,5和6例,mTOR的高表达分别为3,4和5例,DJ-1和mTOR在高级别和复发性良性脑膜瘤中均呈高表达状态（P〈0.05）。mTOR与DJ-1的表达有关（P〈0.05）,DJ-1,mTOR的表达强度与良性脑膜瘤的复发有关（P=0.001）。结论：DJ-1和mTOR的高表达可能促进了良性脑膜瘤的复发,结合组织学分级,二者的高表达可能是预测良性肿瘤复发的有临床价值的生物学指标。     

浸润性乳腺癌中AR的表达及其预后意义

目的探讨乳腺癌中AR表达与临床病理特征的关系及预后意义。方法采用免疫组化EnVision法检测584例浸润性乳腺癌中AR、ER、PR、HER-2及Ki-67的表达,对比分析AR表达与临床病理特征及预后的相关性。结果单因素分析显示,584例乳腺癌中AR阳性率为86.5%,AR表达与患者年龄、肿块大小、WHO分级、ER、PR、Ki-67、HER-2、分子分型有关(P0.05)。多因素Logistics回归分析显示,AR表达与患者年龄、WHO分级、ER、HER-2有关(P0.05)。生存分析表明,ER~+/AR~+组患者无复发生存(relapse free survival, RFS)、总生存(overall survival, OS)、无远处转移生存(distant metastasis-free survival, DMFS)明显高于ER~+/AR~-组(P0.05);ER~-/AR~+组患者的RFS、OS、DMFS则明显低于ER~-/AR~-组(P0.05)。结论 AR在浸润性乳腺癌中有较高的阳性率,AR在ER~-和ER~+这两类乳腺癌发生、发展中的生物学功能有明显差异,ER~+/AR~+乳腺癌患者与ER~-/AR~+者相比,有更好的预后。     

脑膜瘤组织中HIF-1α、EphA2蛋白的表达及意义

目的探讨缺氧诱导因子-1α(hypoxia-inducing factor-1α, HIF-1α)与上皮细胞激酶(epithelial kinase A2, EphA2)在脑膜瘤组织中的表达,及与脑膜瘤分级、预后的关系。方法采用免疫组化SP法和Western blot法检测脑膜瘤中EphA2和HIF-1α的表达,分析HIF-1α、EphA2表达与脑膜瘤临床病理特征的关系。结果 68例脑膜瘤中,HIF-1α蛋白高表达32例(47.1%),低表达36例(52.9%);EphA2蛋白高表达35例(51.5%),低表达33例(48.5%);且HIF-1α和EphA2表达与脑膜瘤分级和复发相关(P0.01)。结论脑膜瘤组织中HIF-1α、EphA2蛋白高表达可能与脑膜瘤患者预后较差相关。     

乳腺癌中雄激素受体的表达及与雌激素、孕激素受体表达的关系

目的 研究乳腺癌组织中雄激素受体(AR)表达的意义及其与雌激素受体(ER)、孕激素受体(PR)表达的关系.方法 应用免疫组化染色检测200例乳腺癌中AR及ER、PR的表达,并结合相关临床病理指标进行比较分析.结果 乳腺癌组织中有113例表达AR,121例表达ER,109例表达PR.在肿瘤＜2cm者中AR阳性率为66.67％(42/63),肿瘤2～5cm者中AR表达率为55.17％ (64/116),肿瘤＞5cm者AR表达率为33.33％(7/21).组织学分级Ⅰ级者肿瘤AR阳性表达率为67.8％(36/53),组织学分级Ⅱ级及Ⅲ级者肿瘤AR的阳性表达率分别为56.5％(61/108)及36.11％(13/36),Ⅰ级及Ⅲ级间比较差异有统计学意义(P =0.0031);AR表达差异与淋巴转移无相关性.AR在乳腺癌中的表达与ER的表达相关(P＜0.001),而与PR的表达无关(P=0.3280).结论 AR高表达的乳腺癌可能具有较好的预后.     

胃癌组织中bcl-2表达与预后的关系

胃癌是严重危害人类健康的常见恶性肿瘤之一,癌细胞浸润、淋巴结转移是胃癌术后复发和化疗失败的主要原因。为阐明bcl-2基因在胃癌发生、发展及预后过程中的作用,检测60例胃癌bcl-2表达情况,探讨与胃癌发展及预后的关系。1材料与方法1.1病例来源60例胃癌均取自张家口地区1996~2     

白血病再生耐药现象及其与Bc1-2基因家族的关系

再生耐药是白血病治疗中的常见现象，与白血病完全缓解期的长短及预后有直接的关系．本文综述了白血病再生耐药现象及其与ＢＣ１－２基因家族的关系．     

mdm2 gene alterations and mdm2 protein expression in breast carcinomas

This study investigates the mdm2 gene status and expression in 66 surgically resected human breast carcinomas, with correlations with clinico-pathological and biological data (histological type, grading, steroid receptor status, p53 expression, proliferative activity). Four (7.7 per cent) out of 52 informative cases bear mdm2 gene amplification (four- to ten-fold) and 8 (15.4 per cent) of 52 cases showed borderline amplification (three-fold). Nine (13.6 per cent) out of 66 cases showed strong mdm2 nuclear immunoreactivity. Twenty-seven (40.9 per cent) cases showed isolated mdm2 reactive nuclei. All cases with clear amplification showed a high percentage of mdm2 immunoreactive nuclei. The relationship between gene amplification and mdm2 protein expression is highly significant (P<0.0001). No association was observed between mdm2 gene amplification and any of the considered clinico-pathological and biological parameters, while mdm2 immunoreactivity showed a significant association only with oestrogen receptor immunoreactivity (P=0.009). p53 expression was associated neither with mdm2 gene amplification nor with mdm2 immunoreactivity. It could be tempting to hypothesize that the evaluation of the combined mdm2/p53 immunohistochemical phenotype in human breast carcinoma could give us better prognostic information than the evaluation of the expression of the p53 protein alone.     

Novel androgen receptor gene mutations in Australian patients with complete androgen insensitivity syndrome

We have identified androgen receptor (AR) gene mutations in eight Australian subjects with complete androgen insensitivity syndrome (AIS). Four individuals, from three families, have novel mutations that introduce premature termination codons. Two siblings have the nonsense mutation Glu681X, and another subject has the nonsense mutation p.Ser884X. The other subject has a CA insertion at codon 829 (c.2847_2848insCA), causing a frameshift mutation that introduces four nonsense amino acids prior to a Stop codon. All the termination codons occur in the ligand binding domain, and cause reduced androgen binding in patient genital skin fibroblasts. Four further patients have missense mutations. One subject has two different mutations, p.Ala645Asp in the hinge region of the receptor, and p.Arg752Gln in the ligand binding domain. Both these mutations have previously been reported in patients with AIS, but the combination of these two mutations in one subject is unique. Another subject has a novel c.2533G>C transversion at the first nucleotide in exon 5, introducing the amino acid change p.Gly724Ala at a highly conserved residue in the ligand binding domain. Androgen binding is normal in fibroblasts from this subject, although other point mutations at this amino acid totally abolish binding. Two other subjects have mutations previously described as causing AIS, namely p.Arg779Trp and p.Val889Met substitutions in the ligand binding domain of the receptor. The p.Arg779Trp mutation is associated with the detection of a truncated AR protein in this patient's fibroblasts, suggesting the mutation renders the receptor susceptible to proteolysis.     

Novel molecular defects in the androgen receptor gene of Mexican patients with androgen insensitivity

The androgen insensitivity syndrome (AIS) is an X-linked form of male pseudohermaphroditism caused by mutations in the androgen receptor (AR) gene. In the present study, we analyzed the AR gene in 8 patients, 4 sporadic and 2 familial cases with the syndrome, using exon-specific polymerase chain reaction, single-stranded conformational polymorphism and sequencing analysis and identified six new single base mutations, including one nonsense mutation at the hinge region of the receptor. These molecular lesions occurred in the steroid-binding domain (SBD) and all but one affected the first nucleotide of their respective codons. A nonsense mutation in exon 4, which converts a glutamine into a premature termination signal (Q657stop), a missense mutation changing arginine instead of glycine (G743R) and a conservative substitution of leucine with valine at amino acid 830 (L830V) were detected in patients with CAIS. Three other missense mutations located in exons 4 (L701I), 5 (A765S), and 6 (Q802R) were present in individuals bearing a partial form of AIS. These data allow us to reaffirm the view that nonsense mutations in the AR results almost invariably in a CAIS phenotype and underly the importance of the SBD for the AR functional activity.     

子宫腺肌症雌激素受体、孕激素受体与bcl-2的表达

目的 探讨雌激素受体（ER）、孕激素受体（PR）和bcl-2在子宫腺肌症中异位和在位内膜的表达及意义。方法 用免疫组化EnVision法检测40例子宫腺肌症在位子宫内膜和肌间异位内膜ER、PR和bcl-2的表达情况。结果 在位和异位子宫内膜组织中均有ER、PR和bcl-2的阳性表达。其中腺上皮阳性表达率高于间质（P〈0．05）,且异位内膜的腺上皮bcl-2阳性表达率高于在位组织（P〈0．05）;ER和PR的表达两者差异无显著性（P〉0．05）。异位内膜腺体ER、PR与bcl-2表达具有相关性（P〈0．01）。结论 子宫腺肌症异位和在位子宫内膜组织中均有ER、PR和bcl-2的阳性表达,可能与子宫腺肌症的发生、发展有关。     

DonnahooⅣ型阴茎弯曲畸形阴茎皮肤及纤维性尿道组织中雄激素受体的表达及临床意义

目的：检测Donnahoo Ⅳ型阴茎弯曲畸形阴茎皮肤及纤维性尿道组织中雄激素受体(androgen receptor,AR)的表达情况,探讨AR异常在疾病发病中的作用及临床意义。方法：以Ⅳ型阴茎弯曲患者25例作为研究对象,手术治疗纠正弯曲畸形,术中收集阴茎背、腹侧皮肤和纤维性尿道组织。以包皮过长患者18例作为正常对照,行包皮环切术收集正常阴茎背、腹侧包皮组织。组织标本经免疫组化LSAB法染色后观测AR表达规律,行统计学分析。结果：AR在正常阴茎包皮和Ⅳ型阴茎弯曲标本中有阳性表达。正常对照阴茎背、腹侧包皮AR阳性表达率为(62.94±5.40)%、(62.87±5.33)%;Ⅳ型阴茎弯曲背、腹侧皮肤和纤维性尿道AR阳性表达率为(58.63±2.66)%、(57.23±2.04)%、(53.71±2.15)%,AR表达较正常对照均显著减少(P<0.05);Ⅳ型阴茎弯曲自身背、腹侧皮肤间相比,AR表达无统计学差异(P>0.05),AR在纤维性尿道的表达较自身皮肤显著减少(P<0.05)。分层分析发现,轻中度弯曲背、腹侧皮肤及纤维性尿道AR阳性表达率为：(59.37±3.11)%、(58.75±3.20)%、(55.48±2.86)%,AR表达较正常对照无统计学差异(P>0.05);重度弯曲背、腹侧皮肤及纤维性尿道AR阳性表达率为：(55.21±3.32)%、(53.69±4.09)%、(46.17±3.65)%,AR表达较正常对照均显著减少(P<0.05);与轻中度弯曲比较,重度弯曲纤维性尿道AR表达显著减少(P<0.05)。结论：Donnahoo Ⅳ型阴茎弯曲畸形阴茎皮肤及纤维性尿道组织中AR表达显著减少,自身背、腹侧皮肤间AR表达并无差异,重度弯曲纤维性尿道AR表达减少更为明显。     

地塞米松对哮喘豚鼠肺组织嗜酸细胞bcl-2表达的影响及意义

目的 研究哮喘豚鼠肺内不同密度嗜酸细胞（Eos）凋亡与bcl-2 mRNA表达的关系及地塞米松（DM）对它们的影响。方法 应用DM干预哮喘豚鼠,分离哮喘豚鼠支气管肺泡灌洗液中不同密度Eos,以TUNEL法检测细胞凋亡,以原位杂交检测bcl-2 mRNA表达。结果 哮喘组Eos凋亡率较正常组明显降低（P〈0．01）,应用DM后均显著增加（P〈0．01）。正常豚鼠Eos可检测到bcl-2 mRNA表达,不同密度Eos表达无显著差异（P〉0．05）。哮喘组bcl-2mRNA明显增加,应用DM后其表达明显减少。结论凋亡调节的缺失是导致组织及血中Eos增多的重要原因,bcl-2参预了哮喘Eos凋亡的调节。DM可促进哮喘肺组织中的Eos细胞凋亡,bcl-2可能是DM调节Eos细胞凋亡的重要途径之一。     

Increased bcl-2 expression in lymphocytes and its association with hepatocellular damage in patients with autoimmune hepatitis

The proto-oncogene product bcl-2 is known to inhibit apoptotic cell death, and its dysregulation might play a critical role in the development of autoimmune disease. To elucidate the role of bcl-2 in autoimmune hepatitis (AIH), its expression in peripheral blood mononuclear cells (PBMC) and in liver-infiltrating lymphocytes (LIL) was investigated. Increased bcl-2 expression in PBMC was found in AIH patients compared with that in chronic hepatitis C (CHC) patients and in healthy controls. The level of bcl-2 expression significantly correlated with serum ALT level. Further analysis showed that CD4+ T cells are enriched in bcl-2-expressing PBMC. To characterize the Th1/Th2 profile of bcl-2-expressing CD4+ T cells, intracellular interferon-gamma (IFN-gamma) and IL-4 were analysed. The results revealed that most of the bcl-2-expressing cells were found to be IFN-gamma-secreting Th1 cells. In three patients for whom their clinical courses could be followed, bcl-2 expression was decreased after the initiation of immunosuppressive therapy with corticosteroids. However, the level of IFN-gamma + cells was not altered. Immunohistochemical analysis also showed that large amounts of bcl-2+ cells were observed in periportal area in the liver. In conclusion, bcl-2-expressing cells were shown to be increased in peripheral blood and liver in AIH and the bcl-2 product was expressed mainly in CD4+ Th1-type cells, suggesting that these cells might promote the cellular immune response and contribute to the development of hepatitis and hepatocellular damage in AIH.     

完全型雄激素不敏感综合征雄激素受体基因突变分析

目的 对完全型雄激素不敏感综合征一家系雄激素受体(androgen receptor,AR)基因进行突变检测;并对发现突变的基因进行分析.方法 应用PCR扩增、DNA序列测定等技术分析所有AR基因外显子及其邻近DNA序列片段;应用核苷酸内切酶诊断方法观察其是否存在于正常人群;应用跨物种比对方法探讨突变所在位置的保守性.结果 3例患者AR基因第4外显子均发生E681D(GAG→GAT)错义突变,患者母亲为此突变杂合子携带者;患者父亲未见异常;正常人群未发现AR基因E681D突变;681位谷氨酸在不同物种间高度保守.结论 AR基因E681D(GAG→GAT)突变可能是导致完全型雄激素不敏感综合征新的突变方式.     

Bcl-2和nm23的表达与乳腺癌生物学行为的关系

目的研究乳腺癌中bcl-2与nm23基因表达的生物学意义及它们之间的相互关系对乳腺癌生物学行为的影响.方法应用免疫组织化学S-P方法对65例乳腺癌石蜡包埋组织进行检测,分析bcl-2与nm23基因表达与乳腺癌病理参数的关系.结果 bcl-2和nm23阳性表达率分别为57.4%、63.1%.bcl-2基因阳性表达与组织学类型、患者年龄、有无淋巴结转移以及肿瘤大小无关(P>0.05);与乳腺癌组织学分级呈正相关(P<0.05),nm23阳性表达与肿瘤大小、组织学类型和患者年龄无关(P>0.05);与乳腺肿瘤的组织学分级和淋巴结转移呈负相关(P<0.05);bcl-2与nm23的表达有相关性(P<0.05).结论 bcl-2阳性表达和nm23阴性的乳腺癌患者细胞恶性程度高,bcl-2与nm23基因共同参与了乳腺癌的发生和发展.