乳腺肿瘤中BCSG1、CD105的表达及意义

目的探讨BCSG1、CD105在乳腺癌发生、发展中的生物学意义。方法采用免疫组织化学技术SP法,检测40例乳腺纤维腺瘤、20例乳腺导管原位癌及62例乳腺浸润性导管癌组织,BC-SG1、CD105的表达情况。结果 BCSG1,CD105表达[微血管密度(MVD)计数]在三组乳腺肿瘤组织中的阳性表达比较差异均有统计学意义(P0.05)。乳腺浸润性导管癌组织中BCSG1、CD105阳性表达率明显升高,提示乳腺肿瘤的浸润和血管生成增强。结论联合检测两种指标的表达状况将有助于乳腺癌的早期诊断和预后判断。     

uPA及VEGF在乳腺癌中的表达及意义

摘要：笔者应用免疫组化方法检测110例原发性乳腺癌患者中uPA及VEGF的表达，并结合临床、病理及随访资料进行分析。 结果示，110例中，uPA高表达者59例，占53.6%；低表达者51例，占46.4%。VEGF高表达者65例，占59.1%；低表达者45例，占40.9%。uPA表达与肿瘤大小、淋巴转移及TNM分期有关，VEGF表达与TNM分期有关；uPA和VEGF的表达与年龄、月经状况、激素受体状况无关；uPA和VEGF高表达者的无病生存期和总生存期均相应低于低表达者的生存期。多因素分析显示，uPA和VEGF均是影响无病生存期和总生存期的独立预后因子。 提示uPA和VEGF与乳腺癌的侵袭转移行为密切相关，两者均可能是预测乳腺癌患者预后的的独立预后因子。     

BRCA1在乳腺肿瘤中的表达及其临床意义

目的探讨乳腺癌易感基因（BRCA1）在乳腺癌和乳腺良性肿瘤中的表达及其临床意义。方法应用ABC免疫组化法检测52例乳腺癌、30例乳腺纤维腺瘤并上皮增生活跃和10例乳腺增生症患者中的BRCA1的表达。结果BRCA1在乳腺癌中的阳性表达率为38％（20／52），在乳腺纤维腺瘤中的阳性表达率为73％（22／30），而10例乳腺增生症患者BRCA1阳性率为90％（9／10）（Χ^2=14．78，P〈0．01），在乳腺癌患者中腋窝有淋巴结转移组的表达率明显低于无淋巴结转移组（Χ^2=15．42，P〈0．01），BRCA1的表达与肿瘤的组织学类型（Χ^2=0．156，P〉0．05）、肿块大小（Χ^2=0．587，P〉0．05）无关。结论BRCA1在乳腺癌的发生发展过程中有重要作用，可能成为临床对乳腺癌诊断和判断预后的一个重要指标，可能对乳腺癌的早期诊断及预防有重要意义。     

肿瘤浸润淋巴细胞在肿瘤免疫研究中的进展

ＴＩＬｓ的应用进入了新阶段，也存在许多亟待解决的问题。本文综述原位ＴＩＬｓ与临床预后的相关性、体外扩增方法及临床应用效果和前景等方面的主要进展。     

p75在乳腺肿瘤中的表达

目的 探讨神经牛长因子低亲和力受体p75在乳腺肿瘤中的表达及其意义.方法 采用PV-9000免疫组织化学方法检测101例乳腺疾病患者病灶组织中p75的表达.结果 p75在乳腺肿瘤肌上皮细胞中均有表达,而在乳腺癌中的表达率明显低于纤维腺瘤、小叶增生、导管内乳头状瘤(P＜0.05),各类乳腺痛中的p75表达未见明显差异(P＞0.05).结论 p75可能抑制乳腺肿瘤细胞的增生,诱导瘤细胞的分化.     

S100A14在消化系统肿瘤中的研究进展

S100A14是多功能S100蛋白家族的成员之一,具有广泛的生物学功能,如细胞增殖、分化与凋亡、侵袭与转移等。它在多种肿瘤中的表达具有细胞和组织特异性,而且表达水平与患者预后相关。S100A14在消化系统肿瘤中,主要通过与靶蛋白结合发挥其作用与功能,但作用机制尚未完全阐明。笔者就S100A14的分子结构与功能,及其在消化系统肿瘤中表达情况及作用机制进行综述。     

DKK-1、VEGF在乳腺癌组织中的表达及其与预后的关系

目的：探讨Dickkopf-1(DKK-1)、血管内皮生长因子（VEGF）与乳腺癌临床特征和预后的关系。方法：选取2014年6月至2016年6月青岛大学附属医院收治的109例乳腺癌患者为研究对象。免疫组织化学法检测乳腺癌组织及癌旁组织中DKK-1、VEGF的表达,分析二者与乳腺癌临床特征间的关系。所有患者出院后随访60个月。Spearman法分析乳腺癌组织DKK-1、VEGF的关系。Kaplan-Meier法分析DKK-1、VEGF与乳腺癌患者预后的关系。COX回归分析影响乳腺癌患者预后的危险因素。结果：与癌旁组织比较,乳腺癌组织DKK-1、VEGF阳性表达率均显著升高（P<0.05）。乳腺癌组织中DKK-1、VEGF阳性表达与患者TNM分期、淋巴结转移有关（P<0.05）。乳腺癌组织中,DKK-1阳性表达与VEGF阳性表达呈正相关（r=0.372,P<0.05）。DKK-1、VEGF阳性表达组患者5年内生存率（51.3%、53.4%）均低于阴性表达组（81.4%、74.5%）。多因素COX分析表明,淋巴结转移、DKK-1、VEGF阳性表达是影响乳腺癌患者预后的危险因...     

BCSG1检测在乳腺癌诊断中的意义

BCSG1是新近发现的一种人类原癌基因，一些研究证实BCSG1在正常乳腺或良性乳腺病变中几乎不表达．而在进展期乳腺癌中有高度表达，且基因表达与乳腺癌肿瘤分期密切相关。我们利用细针穿刺（fine needle aspiration，FNA）所得的细胞，同时作细胞学诊断和RT-PCR检测BCSG1 mRNA表达，比较二者在诊断学上的一致性和互补性．以期找到一项新的可靠的乳腺癌诊断方法。     

维生素D受体在乳腺肿瘤中的表达及其临床意义

目的 探讨维生素D受体(VDR)在乳腺肿瘤中的分布及其与乳腺癌临床病理因素的关系.方法 采用免疫组织化学SP法对51例乳腺癌组织及20例乳腺良性肿瘤组织进行ER,PR,HER2和VDR检测,分析VDR与乳腺癌患者年龄、绝经状况、肿瘤大小、有无腋窝淋巴结转移、临床分期、病理类犁及组织学分级的关系.对VDR与ER,PR及HER2 3种受体在乳腺癌中的表达率以及表达强度之间的关系进行等级相关性分析.结果 VDR在乳腺癌中的表达高于乳腺良性肿瘤(χ~2=4.23,P＜0.05),乳腺癌中VDR的表达强度与PR,HER2的表达强度呈正相关(r_(sPR)=0.295,P＜0.05;r_(sHER2)=0.296,P＜0.05).结论 VDR可能影响乳腺癌的发生;维生素D治疗可能提高PR阳性患者内分泌治疗的效果,改善HER2阳性患者的预后.     

S100p在胰腺癌组织中的表达及其临床意义

目的探讨S100p蛋白在胰腺癌组织中的表达及其临床意义。方法应用免疫组化SP法检测58例胰腺癌组织中S100p蛋白的表达情况,分析其与临床病理因素的关系及对胰腺癌预后的影响。结果在胰腺癌组织中S100p蛋白的表达率为87.9%(51/58),而在胰腺癌旁组织中S100p蛋白无表达;S100p蛋白在癌组织中表达明显高于癌旁组织,差异有统计学意义(P0.05)。S100p表达与胰腺癌的组织分化程度、临床分期、淋巴结转移有关;该3因素的分组间均有统计学差异(P0.05)。S100p在胰腺癌组织中的表达与患者预后有关;S100p阴性组胰腺癌患者与阳性组生存曲线有明显差别,前者的预后明显优于后者。结论 S100p在胰腺癌发生、发展中发挥重要作用,可能成为诊断胰腺癌新的标志物以及判断其生物学行为、预测转移趋势的指标。     

Vascular endothelial growth factor receptor 2, but not S100A4 or S100A6, correlates with prolonged survival in advanced urothelial carcinoma

ObjectiveA major challenge in muscle-invasive urothelial carcinoma (UC) is to identify biomarkers that can predict disease prognosis and treatment response after cystectomy. Therefore, we analyzed the potential prognostic value of the proteins vascular endothelial growth factor receptor 2 (VEGFR2), S100A4, and S100A6 in UC.MethodsRetrospective outcome data and tumor specimens from 83 cystectomy patients with histologically confirmed invasive UC were included. Expression levels of VEGFR2 (also called flk-1 and KDR), S100A4, and S100A6 were analyzed in primary tumor tissue by immunohistochemistry.ResultsImmunohistochemical staining and analysis of VEGFR2, S100A4, and S100A6 showed localization mainly in tumor cell cytoplasm. High VEGFR2 expression and low tumor category were independent variables associated with longer overall survival (OS) and disease-free survival, revealed by a bivariate Cox proportional hazards regression model (both P<0.001). In addition, the univariate log-rank test and the Cox model demonstrated that OS beyond 2 years was significantly greater among patients with low S100A6 expression than in those with high S100A6 expression (P = 0.017 and 0.022, respectively). Differences in tumor expression of S100A4 were not significantly associated with outcome.ConclusionIn this study, VEGFR2 expression was significantly correlated with risk of disease relapse and OS in a defined cohort of patients with UC of the bladder treated by cystectomy.     

Cav-1 mRNA、S100A4 mRNA 和 CD31 的表达与前列腺癌转移及生存率关系的研究

目的 研究前列腺癌组织中Cav-1 mRNA、S100A4 mRNA和CD31的表达,探讨其与前列腺癌转移及生存率的关系. 方法 选取2004年1月至2006年5月行前列腺癌根治术切除的癌组织标本42例和癌旁组织12例.患者年龄58 ～ 86岁,平均(71.6±7.6)岁.Gleason评分≤6分17例,7分12例,≥8分13例.TNM分期:T116例,T29例,T311例,T46例.骨转移8例,无骨转移34例.术前PSA＜4μg/L 4例,4～ 10 μg/L 10例,＞10 μg/L 28例.12例前列腺癌旁组织作为对照组,取自距离肿瘤1 ～2 cm或另一叶(镜下验证无癌细胞)的正常前列腺组织.采用原位杂交法检测42例前列腺癌切除标本和12例癌旁组织中Cav-1 mRNA、S100A4 mRNA的表达;用CD31标记血管内皮细胞,计数肿瘤组织的微血管密度( microvessel density,MVD);结合临床资料分析三者与前列腺癌Gleason评分、TNM分期、PSA值及有无骨转移等特性的关系. 结果 前列腺癌组织中Cav-1 mRNA 和S100A4 mRNA阳性表达率分别为35.7％ (15/42)和47.6％ (20/42),癌旁组织分别为0和8.3％(1/12),各组比较差异均有统计学意义(P＜0.05).Cav-1 mRNA和S100A4 mRNA阳性表达率均与前列腺癌Gleason评分、TNM分期及骨转移呈正相关.Cav-1 mRNA、S100A4 mRNA阴性表达者MVD分别为(62.8±10.4)/mm2和(63.3±12.0)/mm2,阳性表达者分别为(83.5±6.7)/mm2和(77.9±11.0 )/mm2,组间比较差异均有统计学意义(P＜0.05).Cav-1 mRNA表达阳性组和阴性组5年生存率分别为46.7％ (7/15)、85.2％ (23/27),组间比较差异有统计学意义(P＜0.05).S100A4 mRNA表达阳性组和阴性组5年生存率分别为50.0％ (10/20)、90.9％( 20/22),组间比较差异有统计学意义(P＜0.05). 结论 Cav-1 mRNA和S100A4 mRNA阳性表达、MVD增高可能与前列腺痛进展、骨转移有关.Cav-1、S100A4均可能促进前列腺癌微血管形成,导致癌细胞骨转移,降低患者生存质最和生存率.     

S100A4和MMP-2在胃癌组织中的表达及与侵袭和转移的关系

目的:通过检测S100A4、基质金属蛋白酶2(matrix metalloproteinase 2,MMP-2)在胃癌组织中的表达,探讨其在胃癌转移中的作用.方法:应用免疫组织化学方法检测S100A4和MMP-2在正常胃黏膜(n=20)、胃癌组织(n=49)中的表达,比较二者在两种组织中的表达差异.结果:S100A4、MMP-2在胃癌组织中的阳性表达率分别为59.18%、67.35%,其染色强度随浸润深度、淋巴结转移和肿瘤分期的增加而增强(P<0.05);在胃癌的不同病理类型和分化程度亚组,S100A4和MMP-2的表达差异均无统计学意义(P>0.05);S100A4在正常胃黏膜组织不表达,MMP-2在正常胃黏膜组织中的表达率为20.00%.两者的表达率均显著低于胃癌组织中的表达率(P<0.01).S100A4和MMP-2在胃癌组织中的表达呈正相关(r=0.661,P<0.001).结论:S100A4、MMP-2在肿瘤侵袭转移中发挥了重要作用,联合检测S100A4和MMP-2的表达可用于评定胃癌的转移潜能.     

S100A8, S100A9, and the S100A8/A9 complex in circulating blood are not associated with prostate cancer risk-A re-evaluation study

BACKGROUND: To evaluate the diagnostic performance of plasma S100A8, S100A9, and the S100A8/A9 complex as novel markers to discriminate between benign and malignant prostatic diseases as recently suggested for S100A9. METHODS: The study included 90 prostate cancer (PCa) patients (pN0M0, n = 50; pN1M0, n = 27; M1, n = 13), 50 controls without PCa, and six patients within 72 hr after radical prostatectomy for repeated measurements. The S100 proteins were analyzed with specific ELISAs. Comparisons were made to the prostate-specific antigen (tPSA) and the ratio of free to tPSA (%fPSA). RESULTS: The plasma concentrations of the S100 proteins in controls had either significantly higher values (S100A8; P = 0.020) or the tendency to higher values compared with the results in PCa patients. Differences between the three PCa groups were almost negligible. No correlation could be found between S100 protein levels and PSA concentration (r(s) = -0.110 to 0.433, P = 0.317-0.433) or prostate volume (r(s) = -0.038 to 0.018, P = 0.676-0.844). Tumor stage and tumor grade had no observed effect on S100 protein concentrations. After prostatectomy, there were discordant elimination kinetics for PSA and the S100 proteins, as the S100 proteins partially increased while PSA continuously decreased. Analyses of receiver-operating curves showed that, compared with PSA, S100A8, S100A9, and S100A8/A9 did not improve the differentiation between patients with and without PCa, while the discrimination ability was significantly lower than that of %fPSA. CONCLUSIONS: Our re-evaluation study showed that S100A8, S100A9, and the complex S100A8/A9 were less indicative than %fPSA and that they are not suitable to replace PSA.     

Serum levels of S100B,S100A1B and S100BB are all related to outcome after severe traumatic brain injury

Summary Objectives. S100B is an established marker of brain damage. Used in the context as a biochemical marker, S100B denotes a measurement of all S100 proteins, including at least one S100B monomer, i.e. the sum of the two dimers S100A1B and S100BB. Almost all published studies are based on this “sum concentration”. However, the brain specificity of S100B has been questioned and increased serum levels have also been reported after trauma without head injury. Since the S100B monomer dominates in the brain, we hypothesised that the S100BB dimer should be better related to outcome after severe traumatic brain injury than S100A1B or the “sum concentration”. Methods. Daily serum samples were collected from 59 patients with severe traumatic brain injury. Three different ELISA methods were used for measurements of S100B, S100A1B and S100BB respectively. Outcome was assessed after one year and categorised according to the Glasgow Outcome Scale. Results. Serum levels of S100B, S100A1B and S100BB followed the same temporal course, with early maximum and rapidly decreasing values over the first days after the trauma. Maximum serum concentrations of each of the parameters were increased in the patient group with an unfavourable outcome compared with those with a favourable outcome (p = 0.01, 0.006 and 0.004, respectively). Conclusion. Both S100A1B and S100BB were related to outcome after severe traumatic brain injury. Even though this study is small, it seems unlikely that separate analyses of the dimers are of any advantage compared with measuring S100B alone. Correspondence: Dr. Karin Nylén, Department of Neurology, Sahlgrenska University Hospital, SE-413 45 G?teborg, Sweden.     

S100A4细胞核表达与胃癌淋巴结转移相关

目的探讨S100A4蛋白在胃癌组织中的细胞内定位及其表达情况及与胃癌临床病理参数的关系。方法分离10对新鲜胃癌组织及配对的正常胃黏膜的核蛋白及浆蛋白，用蛋白印迹法检测S100A4蛋白在细胞内的定位。用免疫组织化学方法检测131例胃癌患者的胃癌组织和20例转移性淋巴结中S100A4蛋白的表达。结果S100A4蛋白在胃癌组织细胞核的表达阳性率为24．4％（32／131）。细胞浆表达阳性率为38．2％（50／131）。在32例S100A4核表达阳性的胃癌病例中，30例（93．8％）有淋巴结转移。伴淋巴结转移的胃癌组织中，S100A4细胞核表达阳性率（29．1％）显著高于没有淋巴结转移的胃癌组织中的S100A4细胞核表达的阳性率（7．1％）（P=0．016）。结论在胃癌组织中发现细胞核表达S100A4，并与胃癌淋巴结转移有关。     

Combined expression of S100A4 and Annexin A2 predicts disease progression and overall survival in patients with urothelial carcinoma

ObjectivesTo determine the expression patterns and prognostic value of S100A4 and Annexin A2 for urothelial carcinoma of the urinary bladder.Methods and materialsImmunohistochemical staining for S100A4 and Annexin A2 was performed in 315 archived radical cystectomies and 63 normal specimens. The immunoreactivity of these proteins was correlated to evaluate their clinical significance as prognostic factors.ResultsProtein levels of S100A4 and Annexin A2 were up-regulated in urothelial carcinoma compared with adjacent nontumor tissues. The increased expressions of S100A4 and Annexin A2 were associated with invasion depth, lymph node metastasis, and distant metastasis (P<0.05). High expression of S100A4 correlated with expression of Annexin A2. These alterations in expression were also associated with greater risk of disease progression and decreased chance of carcinoma-specific survival. Further multivariate analysis suggested that expressions of S100A4 and Annexin A2 were independent prognostic indicators for overall survival in urothelial carcinoma. The patients with S100A4-positive/Annexin A2-positive carcinomas presented the lowest 5-year survival rate compared with the other 3 groups.ConclusionsS100A4 and Annexin A2 proteins could be useful prognostic markers to predict tumor progression and prognosis in urothelial carcinoma. The expression patterns of S100A4/Annexin A2 interaction correlated well with the pathologic stage, disease progression, and carcinoma-specific survival. This finding could aid in identifying more biologically aggressive carcinomas and thus patients who might benefit from more intensive adjuvant therapy.     

BCSG1基因在乳腺癌新辅助化疗疗效评估中的价值

目的:探讨乳腺癌特异基因（BCSG1）在乳腺癌新辅助化疗疗效评估中的价值。方法:采用免疫组化S P法和荧光定量PCR方法检测36例乳腺癌患者新辅助化疗(CEF方案)前后乳腺癌组织BCSG1的表达，比较化疗前后肿瘤体积的变化情况，分析新辅助化疗前后BCSG1蛋白表达与肿瘤形态学变化的关系。结果:36例乳腺癌患者新辅助化疗后肿瘤体积均有明显缩小（P<0.01），病灶缓解率(CR+PR)为85.6%；新辅助化疗后BCSG1 mRNA表达水平亦明显低于化疗前（P<0.05），BCSG1蛋白高表达率低于新辅助化疗前（P<0.01）。结论:乳腺癌新辅助化疗后BCSG1在分子和蛋白水平表达均明显降低，与新辅助化疗后疗效呈负相关（r=-0.539,P<0.01），提示BCSG1可作为乳腺癌新辅助化疗疗效的预测因子。     

S100A4和血管内皮生长因子C、D在胃癌组织中的表达及其与淋巴结转移和预后的关系

目的 观察人胃癌S100A4和血管内皮生长因子(VEGF)-C、VEGF-D的表达,探讨其与临床病理特征及预后的关系.方法 应用免疫组织化学方法检测108例人胃癌及20例癌旁组织中S100A4和VEGF-C、VEGF-D的表达.分析S100A4和VEGF-C、VEGF-D表达与患者年龄、性别、肿瘤大小、病理类型、浸润深度、淋巴结转移和肿瘤TNM分期的关系,并作预后分析.结果 S100A4和VEGF-C、VEGF-D在胃癌组织中的阳性率明显高于癌旁组织(P＜0.05).S100A4的表达与肿瘤大小和淋巴结转移有关(P＜0.05),VEGF-C的表达与淋巴结转移和TNM分期有关(P＜0.05),VEGF-D的表达与淋巴结转移和TNM分期无明显相关(P＞0.05),肿瘤组织内S100A4和VEGF-C两者表达呈正相关(P＜0.05).S100A4和VEGF-C、VEGF-D阳性胃癌患者5年生存率分别低于阴性患者,差异无统计学意义(P＞0.05).结论 S100A4和VEGF-C的表达与胃癌的淋巴结转移有关,S100A4可能参与VEGF-C淋巴管生成通路,在胃癌的淋巴结转移中发挥重要作用.