子宫内膜癌组织中生长抑素受体、VEGF的表达及其与血管形成的关系

目的探讨生长抑素受体（somatostatin receptor,SSTR）、血管内皮生长因子（vascular endothelial growth factor,VEGF）在子宫内膜癌组织中的表达及其与肿瘤血管形成的关系。方法应用免疫组织化学方法检测60例子宫内膜癌组织中SSTR各亚型、VEGF及CD34标记的微血管密度（microvessel denisity,MVD）的表达情况,探讨其与子宫内膜癌临床病理学特征及肿瘤血管形成的关系。结果在60例子宫内膜癌组织中,SSTR各亚型（SSTR1、SSTR2、SSTR3、SSTR4及SSTR5）的阳性表达率分别为70．0％,15．0％。21．7％,23．3％及18．3％;SSTR3、SSTR4在中高分化组表达阳性率明显高于低分化组（P〈0．05）。VEGF的阳性表达率为83．3％,VEGF在低分化组表达阳性率明显高于中高分化组、深肌层浸润组表达阳性率明显高于浅肌层浸润组、FIGO分期≥II期组表达阳性率明显高于I期组（P〈0．05）。子宫内膜癌组MVD（44．85±15．78）明显高于正常子宫内膜组MVD（18．96±4．30）（P〈0．01）。SSTR5的表达与VEGF呈负相关,VEGF阳性表达组子宫内膜癌组织MVD高于VEGF阴性组。结论联合检测SSTR和VEGF对子宫内膜癌预后的评估有一定临床意义。生长抑素类似物（somatostatin analogs,SSTA）可能为子宫内膜癌的诊治提供新的靶点。     

血管紧张素Ⅱ受体1、VEGF和MVD在乳腺癌中的表达及相关性研究

目的:研究AT1受体、VEGF和CD34在乳腺癌中的表达、并探讨其相关性及临床意义。方法:该实验采用免疫组化方法(SP法),对102例乳腺癌患者石蜡包埋切片中的AT1受体、VEGF和CD34进行检测。结果:AT1受体在乳腺癌中阳性表达率为48%,在乳腺癌中有腋淋巴结转移组为61．8%,无腋淋巴结转移组为31．9%,两者差别有统计学意义(P＜0．05)。VEGF在乳腺癌中表达率为40．2%,有腋淋巴结转移组44．4%,无腋淋巴结转移组为23．5%,两者差别有统计学意义(P＜0．01)。AT1R阴性表达组的VEGF阳性表达率为11．3%(6/53),AT1R阳性表达组的VEGF阳性表达为71．4%(35/49),两者差别有统计学意义(P＜0．05); AT1R阴性表达组的MVD值为17．35±5．67,AT1R阳性表达组的MVD值为20．37±7．30,两组差别有显著性(P＜0．05)。VEGF阴性表达组的MVD表达率为17．14±5．78,VEGF阳性表达组的MVD表达为21．27±7．14,两组差别有统计学意义(P＜0．05)。结论:乳腺癌组织中AT1受体的阳性表达率为48%(49/102)AT1受体表达与患者年龄、肿瘤大小、ER、PR无相关性,而与腋淋巴结转移成正相关;乳腺癌组织中VEGF的阳性表达率为40．2%(41/102),VEGF表达与患者年龄、肿瘤大小、ER、PR无相关性,而与腋淋巴结转移成正相关;AT1受体表达与VEGF表达成正相关。在乳腺癌组织中MVD和AT1R和VEGF表达均成正相关。     

CD31和CD105在卵巢上皮性肿瘤中的表达及其临床病理意义

目的探讨CD31和CD105在卵巢上皮性肿瘤及正常卵巢组织中的表达情况及其与卵巢肿瘤生物学行为之间的关系,并比较同为肿瘤血管内皮标记物的CD31和CDl05在标记微血管方面的差异。方法收集天津市肿瘤医院临床、病理和预后资料完整的恶性卵巢上皮性肿瘤组织标本76例,病例标本采用免疫组化EnVision法检测CD31和CD105所标记的MVD数值,MVD计数参照Weidner方法进行量化分析,实验同时取20例交界性卵巢上皮性肿瘤、10例良性卵巢上皮性肿瘤和10例宫颈癌手术中切除的正常卵巢组织作为对照。结果①CD31蛋白在卵巢上皮性肿瘤的微血管和大血管上均有较强表达,在正常卵巢组织血管中亦有表达,恶性卵巢肿瘤中的MVD-CD31值（5．484-_0．75）显著高于交界性卵巢肿瘤（2．24±0．61）、良性卵巢肿瘤（2．24土0．41）及正常卵巢组织（1．20±0．37）（P〈0．01）;在卵巢癌中,MVD-CD31值仅与有无淋巴结转移及组织学分级之间的差异有统计学意义（P〈O．05）,而与年龄、病理类型、肿瘤大小、腹水、有无远处转移无关（P〉0．05）。②CDl05蛋白在卵巢肿瘤微血管中有表达,在正常卵巢组织中呈微弱表达或无表达,恶性卵巢肿瘤中的MVD-CDl05值（4．07士2．11）显著高于交界性卵巢肿瘤（2．08土0．30）、良性卵巢肿瘤（1．92±1．15）及正常卵巢组织（O．68±0．39）（P〈0．05或P〈0．01）;在卵巢癌中MV口CDl05值与组织学分级、有无腹水、有无远处转移、有无淋巴结转移有关（P〈0．05）,而与年龄、病理类型、肿瘤大小等因素无关（P〉0．05）。③恶性肿瘤组织中的MVD-CD31值显著高于MVD-CDl05值（P〈0．05）。结论在标染卵巢癌方面,CDl05比CD31有明显优越性,CDl05的表达与卵巢癌的生物学行为密切相关,MVD-CDl05值的检测可更准确的确定肿瘤的临床分期、指导治疗及判断预后。     

OSAHS患者腭咽组织中COX-2、VEGF的表达及其与新生血管生成的关系

目的：探讨阻塞性睡眠呼吸暂停低通气综合症（OSAHS）患者腭咽组织中环氧化酶-2（COX-2）、血管内皮生长因子（VEGF）的表达及其与新生血管生成的关系及意义。方法：经多导睡眠监测仪（PSG）确诊的40例OSAHS患者（其中轻度组7例,中度12例,重度21例）及6例无鼾症患者的软腭组织,采用HE染色光镜观察腭咽部组织的病理组织学改变,免疫组化技术检测COX-2,VEGF及微血管密度（MVD）的表达情况。结果：COX-2、VEGF主要表达于OSAHS患者软腭组织的黏膜鳞状上皮和导管腺上皮,中、重度OSAHS组与对照组比较,COX-2,VEGF,MVD表达均有显著差异（P〈0.01）,OSAHS组明显高于对照组,轻度组与对照组差别无统计学意义（P〉0.05）;COX-2、VEGF均与MVD的表达呈正相关（P〈0.01）,COX-2与VEGF的表达呈正相关（P〈0.01）,COX-2,VEGF,MVD均与睡眠呼吸暂停低通气指数（AHI）呈正相关（P〈0.01）,与夜间最低氧饱和度呈负相关（P〈0.01）。结论：OSAHS患者腭咽部存在新生血管增生,与缺氧程度有关,COX-2及VEGF在其发生发展过程中可能起到重要作用。     

血管内皮生长因子( VEGF) 在大肠癌中的表达及临床意义

目的：探讨VEGF（Vascular endothelial growth factor）在大肠癌中的表达及与肿瘤大小、病理分级、临床分期和预后的关系。方法：大肠癌组织蜡块50例、癌旁组织20例、正常组织20例。采用免疫组化S—P法对标本切片进行染色。结果：VEGF在癌组织中表达明显高于癌旁组织和正常组织,三者之间差异显著（P〈0．05）。VEGF抗原表达与病理分级、Dukes分期呈负相关性（P〈0．01）。结论：VEGF与大肠癌的发生有关,VEGF的检测可作为大肠癌预后评估的客观指标。     

MMP - 9、VEGF、bFGF 在非何杰金淋巴瘤的表达及临床意义

目的：探讨MMP-9、VEGF、bFGF在非何杰金淋巴瘤（NHL）中的表达及意义。方法：免疫组化法。结果MMP-9、VEGF、bFGF在NHL中表达率分别为43．66％、33．80％、25．35％,均高于正常淋巴结组织中的表达,差异均有显著性（Pm=0．0023,Pv=0．001,Pb=0．0049）。组5年生存率明显低于MMP-9（-）组（P=0．008）。VEGF在T细胞型中表达率高于B细胞型（P=0．019）,VEGF阳性组治疗缓解率低（P=0．045）。巨块型NHL中bFGF表达率较高（P=0．028）,bFGF（＋）组5年生存率明显低于bFGF（-）组（P=0．041）。MMP-9、VEGF、bFGF之间无协同表达。结论：MMP-9、VEGF、bFGF在NHL中的表达高于正常淋巴组织,可能与淋巴组织恶变有关。MMP-9、bFGF均与生存期呈负相关,是NHL预后差的指标,联合检测更有助于判断预后。VEGF阳性组治疗效果差,提示VEGF阳性NHL患者加用VEGF靶向治疗可能会提高疗效。     

胃癌组织中Tenascin、MVD、Ki-67的表达及其临床意义

目的：探讨胃癌组织中Tenascin蛋白、微血管密度（microvascular density,MVD）、Ki-67的表达及其与临床病理特征的关系。方法：采用免疫组化Elivision法检测70例胃癌组织和20例癌旁正常组织中Tenascin、CD34和Ki-67的表达。结果：①正常胃黏膜上皮Tenascin阴性,胃癌中的Tenascin主要表达于肿瘤相关纤维母细胞的胞质中,且与胃癌的Lauren分型、分化程度、临床分期、淋巴结转移显著相关（P〈0．05）;②胃癌中MVD和Ki-67-LI（标记指数）均高于正常胃黏膜（P〈0．001）,且均与胃癌的临床分期、浸润深度、淋巴结转移显著相关（P〈0．05）;结论：胃癌组织中Tenascin可抑制胃癌的演进,MVD及Ki-67可作为胃癌患者预后的预测指标,联合检测胃癌组织Tenascin、MVD、Ki-67的表达情况,对于进一步了解胃癌的生物学行为和判断预后具有一定的临床价值与意义。     

乳腺癌组织中转化生长因子-β1和血管内皮生长因子的表达及其与血管生成的关系

目的:研究转化生长因子-β1(transforming growth factor-β1,TGF-β1)和血管内皮生长因子(vascular endothelial cell growth factor,VEGF)在乳腺癌组织中的表达及其与血管生成的关系。方法:选取65例手术切除乳腺癌蜡块标本及其周围正常乳腺组织,分为两组:A组为对照组,检测标本为乳腺癌癌旁正常乳腺组织;B组为实验组,检测标本为乳腺癌组织,采用免疫组织化学染色和形态计量检测TGF-β1和VEGF在乳腺癌组织中的表达。利用CD34相关抗原标记血管内皮细胞,计数微血管密度(intratumoral mier oveseulardensity,MVD),并分析其与TGF-β1和VEGF表达的关系。结果:65例乳腺癌组织中,TGF-β1的阳性表达率为69.23%(45/65),TGF-β1阳性表达者MVD值(25.31±4.05)显著高于TGF-β1阴性表达者(21.23±4.29);VEGF的阳性表达率为78.46%(51/65),VEGF阳性表达者MVD值(26.62±3.41)亦明显显著高于VEGF阴性表达者(18.95±6.52)(均P0.05)。不同病理类型的乳腺癌组织中TGF-β1、VEGF的阳性表达率比较差异无统计学意义(P0.05),但TGF-β1、VEGF的阳性表达与乳腺癌的组织分级、淋巴结转移呈显著正相关(均P0.05),且组织学分级越高、淋巴结转移越多,MVD值越大。结论:TGF-β1与VEGF在乳腺癌组织的表达高于正常乳腺组织,并与乳腺癌肿瘤血管的生成有关,二者有望作为乳腺癌恶性程度、浸润转移等生物学行为的评估指标。     

乳腺癌组织中VEGF—C和p38MAPK的表达及与伴淋巴结转移的关系

目的探讨乳腺浸润性导管癌组织中血管内皮生长因子C（VEGF—C）和丝裂原激活蛋白激酶p38（p38MAPK）的表达关系,以及与乳腺浸润性导管癌淋巴结转移等生物学行为的关系。方法采用免疫组织化学sP法检测70例乳腺浸润性导管癌组织及15例癌旁正常组织中VEGF-C和p38MAPK蛋白的表达,并采用Westernblot法检测13例伴有淋巴结转移的乳腺癌及12例无淋巴结转移的乳腺癌的新鲜组织中VEGF—C和p38MAPK蛋白表达。结果VEGF—C和p38MAPK在乳腺浸润性导管癌组织中的表达（阳性率分别为67．0％和61．4％）明显高于癌旁正常组织;VEGF-C和p38MAPK蛋白在伴有淋巴结转移组的乳腺癌组织中的表达均高于无淋巴结转移组（P=0．005,P=0．005）;在乳腺浸润性导管癌组织中VEGF-C和p38MAPK表达存在显著正相关（r=0．383,P=0．001）,并与乳腺浸润性导管癌的TNM分期（P=0．019,P=0．010）有关;VEGF-C和p38MAPK蛋白表达与乳腺浸润性导管癌肿块的大小（P=0．203,P=0．086）和患者的年龄（P=0．0．266,P=0．087）无明显关系。Western blot也证实,VEGF-C和p38MAPK蛋白在有淋巴结转移组中表达高于无淋巴结转移组。结论VEGF-C和p38MAPK的蛋白表达与乳腺浸润性导管癌的淋巴结转移密切相关,其有望成为乳腺癌治疗的新靶点。     

乳腺癌组织中ER、PR、C-erbB-2、CD44V6、Ki67表达的相关分析及临床意义

目的：探讨乳腺癌组织中ER、PR、C-erbB-2、CD44V6和Ki67的表达与年龄、肿瘤大小、临床分期、淋巴结转移的关系以及它们相互之间的线性关系,同时分析其在乳腺癌的发生、发展中所表现出的临床作用和意义。方法：采用免疫组化S—P法检测103例乳腺癌标本中ER、PR、C-erbB-2、CD44V6和Ki67的表达,并与临床病理因素进行相关性分析。结果：103例患者中ER阳性的有57例（55．34％）,PR阳性的有49例（47．57％）,C-erbB．2阳性的有39例（37．86％）,CD44V6阳性的有68例（66．02％）,Ki67阳性的有例（90．29％）,其中以Ki67的表达率最高,C—erbB．2的表达率最低;不同年龄、淋巴结是否转移对ER、PR、C—erbB-2、CD44V6和Ki67表达量的差异。无统计学意义（P〉0．05）;PR的表达与乳腺癌临床分期相关（P〈0．05）,临床分期越高,PR的表达量越低;C．erbB．2的表达与肿瘤大小相关（P〈0．05）,肿瘤组织越小,C—erbB-2的表达量越低;ER的表达量和CD44V6的表达量的差异,有统计学意义（P〈0．05）。结论：在乳腺癌发病率越来越高的中国以至世界,免疫组化检测ER、PR、C—erbB-2、CD44V6和Ki67的阴阳性表达,可以作为乳腺癌发生、发展的评价指标,联合检测更加有助于早期乳腺癌患者的临床治疗和预后判断,减轻乳腺癌患者的身体和心理的痛苦,为临床医生选择和评估乳腺癌患者的治疗方案提供一些参考,更为下一步的个体化治疗和基因治疗做了一些前序工作。     

Expressions of ER,PR, HER-2, COX-2, and VEGF in Primary and Relapsed/Metastatic Breast Cancers

In the present study, we evaluated expressions of estrogen receptor (ER), progestin receptor (PR), human epidermal growth factor receptor-2 (HER-2), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) in primary and relapsed/metastatic breast cancers to elucidate the clinical significance of these markers. The markers were evaluated by immunohistochemistry in specimens of 50 patients with primary or metastatic breast cancer. Positive rates of ER were significantly (p = 0.002) higher in primary versus relapsed/metastatic breast cancer (70 vs. 38 %, respectively). The VEGF positive expression rates were also significantly higher in primary versus metastatic cancer (82 vs. 38 %, respectively; p < 0.001). By contrast, positive rates of HER-2 and COX-2 were not significantly different between different types of cancer. COX-2 correlated with HER-2 expression in both primary and relapsed/metastatic focuses of breast cancer. COX-2 also correlated with VEGF expression in primary breast cancer. Expressions of ER, PR, HER2, and COX-2 did not correlate between primary and relapsed/metastatic breast cancers, indicating that the treatment decision should be made according to the status of these markers in relapsed/metastatic focuses. The total change rates of ER, PR, HER-2, COX-2, and VEGF were 26, 18, 10, 30, and 58 %, respectively. In conclusion, HER-2 and COX-2, along with VEGF, appear to play a role in the development and progression of breast cancer. In addition, all of the studied markers may serve as indicators of prognosis.     

COX-2 and CCR2 induced by CD40 ligand and MCP-1 are linked to VEGF production in endothelial cells

Recent studies have reported that expression of MCP-1 and its receptor, CCR2; and CD40-CD40 ligand (CD40L) interaction on mesenchymal cells play important roles in tumor development. Studies have also connected MCP-1, CCR2, and CD40L to COX-2 expression. The aim of this study was to examine the effect of MCP-1/CCR2 and CD40-CD40L interaction on COX-2 and VEGF expression in endothelial cells. We also investigated the localization of these proteins in gastric cancer tissue. COX-2 and CCR2 levels were evaluated in CD40L-stimulated HUVECs by Western blot and real-time PCR. VEGF secreted in the culture media was quantified by ELISA. Localizations of MCP-1, CD40L, CD34, CD40 and CCR2 in 34 gastric cancer tissue specimens were evaluated by immunohistochemistry. CD40-CD40L interaction-induced COX-2 production and subsequently, upregulated COX-2 production contributed to elevated VEGF and CCR2 levels in CD40L-stimulated HUVECs. CD40L-stimulated VEGF production was COX-2 but not COX-1 dependent. RS-102895, a CCR2-specific antagonist, significantly reduced VEGF production in CD40L- and MCP-1-stimulated HUVECs. MCP-1 had a synergistic effect on COX-2, CCR2 and VEGF levels in CD40L-stimulated HUVECs. In gastric cancer tissue, there was significant correlation between microvessel density and scores for CD40L, MCP-1 and CCR2 protein expression. Thus, MCP-1 had a synergistic effect on COX-2 and CCR2 protein expression in CD40L-stimulated HUVECs and thereby stimulated VEGF production in these cells.     

Regulatory T cells increase in breast cancer and in stage IV breast cancer

Expression levels of VEGF and Her-2, levels of T-regulatory (Treg) cells, levels of CD3+ cells, and ratios of Th (CD4+ T cells)/Tr (Treg) cells were compared between stage I, II, III, and IV breast cancer patients (n?=?120) prior to chemotherapy and healthy women (n?=?30). Cells from peripheral blood were counted by flow cytometry, Her-2 and VEGF expression was detected by pathological examination, and Her-2 was detected by FISH. Breast cancer patients had more Treg cells and a lower ratio of Th/Tr cells than the healthy women. Stage IV breast cancer patients had more Treg cells and a lower ratio of Th/Tr cells than stage I, II, or III breast cancer patients. Patients positive for VEGF had a lower ratio of Th/Tr cells compared with patients negative for VEGF, and those positive for both VEGF and Her-2 also had a lower ratio of Th/Tr cells compared with patients not positive for both VEGF and Her-2. The decreased Th/Tr cells ratio indicates impaired immune function, suggesting that the stage IV breast cancer and the Her-2/VEGF-positive breast cancer patients have lower immune function.     

血管内皮标记物及血管内皮生长因子在胸水细胞中的表达和意义

探讨CD31、CD34、CD105及VEGF在胸水中的表达.应用免疫细胞化学染色,免疫荧光染色,Western-blot技术检测200例非小细胞肺癌患者胸水、30例增生胸水和20例炎性胸水中CD31、CD34、CD105及VEGF的表达.CD31、CD34、CD105及VEGF在非小细胞肺癌胸水中的表达量明显高于增生和炎性胸水表达(P＜0.05).非小细胞肺癌胸水患者CD31、CD34、CD105及VEGF高表达,并且在存在着肿瘤细胞血管样管型结构中表达量明显高于未发现肿瘤细胞血管样管型的胸腔积液.检测CD31、CD34、CD105及VEGF在胸腔积液中的表达情况可能对判断患者的预后有一定价值.     

脑脊液中转移性腺癌细胞免疫表型的变化

目的探讨脑脊液中转移腺癌细胞在没有血供的条件下的生长特征,是否有血管内皮标记物CD34,CD105,FⅧ,淋巴管内皮标记物D2_40及碱性成纤维生长因子(b-FGF)的表达,并促进肺癌的脑转移及肿瘤细胞自我生存的调控。方法采集109例腺癌脑转移患者的脑脊液为研究对象,其中肺癌脑转移107例(包括49例肺癌术后5年内脑转移,58例无肺癌病史直接经脑脊液穿刺发现肺癌脑转移),乳腺癌2例。以40例主要成分为炎性细胞的脑脊液及40例原发性肺腺癌组织标本为对照,采用免疫化学染色方法检测脑转移腺癌细胞及腺癌组织中CD34,CD105,FⅧ,D2_40,b-FGF,VEGF及vimentin的表达。结果 109例脑脊液标本中,CD34,CD105,FⅧ,D2_40,b-FGF及VEGF在转移癌细胞中的阳性率分别为64.2%,67.9%,66.9%,63.8%,56.8%,70.6%明显高于脑脊液对照组(阳性率均为0)且差异具有统计学意义(P0.05)。vimentin在脑脊液转移腺癌细胞中阳性表达,表达率为88.1%。在原发肺癌标本中,CD34,CD105,FⅧ和VEGF表达较弱或不表达。D2-40在癌中不表达。B-FGF与Vimentin在原发肺腺癌中的表达率分别为50.1%和29.3%。结论在肺癌脑转移过程中,肿瘤细胞能够表达不同的血管生长因子,提示可能具备内皮细胞的生物学特性,可能有助于增强肿瘤细胞的转移能力和对环境的耐受能力。     

乳腺癌及癌前病变血管生成相关分子的表达及意义

目的探讨血管生成异常与乳腺癌发生发展的关系。方法采用免疫组化方法检测30例正常乳腺,30例普通性增生,30例非典型增生（AH）,20例导管内癌,50例浸润性导管癌组织中微血管密度（MVD）、VEGF及受体Flk-1/KDR的表达变化。结果各组CD34、VEGF及Flk-1/KDR的表达程度不同,浸润性导管癌组最高。随病程演进,MVD增加（P〈0.05）,VEGF及其受体Flk-1/KDR在血管内皮细胞表达渐进增高（P〈0.05）,但在病程初期各主要指标改变不明显,显著变化始于AH阶段。MVD在AH与导管内癌组间差异不显著（P〉0.05）,VEGF及Flk-1/KDR的表达在AH与导管内癌组间有显著差异（P〈0.05）。结论血管生成在乳腺癌发生发展过程中起着重要作用,血管生成异常可能是乳腺癌发生过程中的早期事件。VEGF及其受体Flk-1/KDR的表达异常可能是乳腺普通性增生-AH-乳腺癌这一癌性转化过程中血管生成异常的主要始动因素,VEGF及其受体Flk-1/KDR可能成为乳腺癌早期诊断及治疗的分子靶标。     

胃癌血管生成素和血管内皮生长因子的表达及其意义

目的探讨血管内皮生长因子(VEGF)和血管生成素(angiopoietin,Ang)在胃癌的表达及其与肿瘤血管生成和临床病理因素的关系。方法采用免疫组化SP法检测84例胃癌和30例癌旁正常组织中VEGF、Ang-1、Ang-2的表达,应用CD34抗体标记微血管内皮细胞,计数微血管密度(MVD),结合临床病理资料进行分析。结果胃癌组织VEGF、Ang-2阳性表达率、MVD值明显高于癌旁正常组织(P(0.05)。VEGF表达与肿瘤大小、侵袭深度、临床分期、淋巴结转移有关(P(0.05),而与患者年龄、性别、组织学类型和分化程度无关,其阳性组的Ang-2阳性表达率、MVD值明显高于阴性组,VEGF的表达与Ang-2、MVD呈正相关。胃癌组织Ang-2表达与肿瘤大小、侵袭深度、淋巴结转移有关(P(0.05),与MVD呈正相关。胃癌Ang-1表达略低于对照组,但无统计学差异(P(0.05),Ang-1的表达与肿瘤侵袭深度和MVD值呈负相关。结论胃癌中VEGF、Ang-2蛋白的过度表达以及Ang-1蛋白的低表达可能在肿瘤血管生成和肿瘤浸润、转移中起重要作用。     

Angiogenesis in male breast cancer

BACKGROUND: Male breast cancer is a rare but aggressive and devastating disease. This disease presents at a later stage and in a more advanced fashion than its female counterpart. The immunophenotype also appears to be distinct when compared to female breast cancer. Angiogenesis plays a permissive role in the development of a solid tumor and provides an avenue for nutrient exchange and waste removal. Recent scrutiny of angiogenesis in female breast cancer has shown it to be of significant prognostic value. It was hypothesized that this holds true in invasive ductal carcinoma of the male breast. In the context of male breast cancer, we investigated the relationship of survival and other clinico-pathological variables to the microvascular density of the tumor tissue. METHODS: Seventy-five cases of primary male breast cancer were identified using the records of the Saskatchewan Cancer Agency over a period of 26 years. Forty-seven cases of invasive ductal carcinoma of the male breast had formalin-fixed paraffin-embedded tissue blocks that were suitable for this study. All cases were reviewed. Immunohistochemical staining was performed for the angiogenic markers (cluster designations 31 (CD31), 34 (CD34) and 105 (CD105), von Willebrand factor (VWF), and vascular endothelial growth factor (VEGF)). Microvascular density (MVD) was determined using average, centre, and highest microvessel counts (AMC, CMC, and HMC, respectively). Statistical analyses compared differences in the distribution of survival times and times to relapse between levels of MVD, tumor size, node status and age at diagnosis. In addition, MVD values were compared within each marker, between each marker, and were also compared to clinico-pathological data. RESULTS: Advanced age and tumor size were related to shorter survival times. There were no statistically significant differences in distributions of survival times and times to relapse between levels of MVD variables. There was no significant difference in MVD between levels of the different clinico-pathological variables. MVD was strongly and significantly correlated between AMC, CMC and HMC for CD31, CD34, and CD105 (p < 0.01) and remained moderate to weak for VWF and VEGF. CONCLUSION: Microvascular density does not appear to be an independent prognostic factor in male breast cancer. However, the likelihood of death for men with breast cancer is increased in the presence of increased age at diagnosis and advanced tumor size. This is perhaps linked to inherent tumor vasculature, which is strongly related throughout a tumor section.     

Targeting tumor vasculature with novel <Emphasis Type="Italic">Listeria</Emphasis>-based vaccines directed against CD105

The FDA approval of bevacizumab (Avastin^®, Genentech/Roche), a monoclonal antibody raised against human VEGF-A, as second-line therapy for colon and lung carcinoma validated the approach of targeting human tumors with angiogenesis inhibitors. While the VEGF/VEGFR pathway is a viable target for anti-angiogenesis tumor therapy, additional targets involved in tumor neovascularization have been identified. One promising target present specifically on tumor vasculature is endoglin (CD105), a member of the TGF-β receptor complex expressed on vascular endothelium and believed to play a role in angiogenesis. Monoclonal antibody therapy and preventive vaccination against CD105 has met with some success in controlling tumor growth. This report describes the in vivo proof-of-concept studies for two novel therapeutic vaccines, Lm-LLO-CD105A and Lm-LLO-CD105B, directed against CD105 as a strategy to target neovascularization of established tumors. Listeria-based vaccines directed against CD105 lead to therapeutic responses against primary and metastatic tumors in the 4T1-Luc and NT-2 mouse models of breast cancer. In a mouse model for autochthonous Her-2/neu-driven breast cancer, Lm-LLO-CD105A vaccination prevented tumor incidence in 20% of mice by week 58 after birth while all control mice developed tumors by week 40. In comparison with previous Listeria-based vaccines targeting tumor vasculature, Lm-LLO-CD105A and Lm-LLO-CD105B demonstrated equivalent or superior efficacy against two transplantable mouse models of breast cancer. Support is provided for epitope spreading to endogenous tumor antigens and reduction in tumor vascularity after vaccination with Listeria-based CD105 vaccines. Reported here, these CD105 therapeutic vaccines are highly effective in stimulating anti-angiogenesis and anti-tumor immune responses leading to therapeutic efficacy against primary and metastatic breast cancer.     

Mesenchymal-to-Endothelial Transition in Kaposi Sarcoma: A Histogenetic Hypothesis Based on a Case Series and Literature Review

Objectives

Although several studies have been conducted regarding Kaposi sarcoma (KS), its histogenesis still remains to be elucidated. The aim of our study was to analyze the immunophenotype of Kaposi sarcoma and to present a hypothesis about the histogenesis of this tumor, based on a case series and a review of relevant literature.

Methods

In 15 cases of KSs diagnosed during 2000–2011, the clinicopathological features were correlated with the immunoexpression of c-Kit, SMA, CD34, CD31, vascular endothelial growth factor (VEGF), COX-2, c-KIT, smooth muscle antigen (SMA), and stem cell surface marker CD105.

Results

Both CD105 and c-KIT rate of the spindle-shaped tumor cell positivity increased in parallel to the pathological stage. All cases displayed CD105 and weak c-KIT positivity in the endothelial cells. SMA, VEGF, and COX-2 were focally expressed in all cases. CD34 marked both endothelium and spindle-shaped tumor cells. No c-KIT expression was noticed in KS of the internal organs.

Conclusions

KS seems to be a variant of myofibroblastic tumors that originates from the viral modified pluripotent mesenchymal cells of the connective tissue transformed in spindle-shaped KS cells, followed by a mesenchymal-endothelial transition and a myofibroblastic-like differentiation. This paper mailnly showed that KS cannot be considered a pure vascular tumor.