淋巴管新生与肿瘤淋巴道转移的相关性

在实体恶性肿瘤中,淋巴道是肿瘤细胞转移的主要途径,淋巴管生成在肿瘤的淋巴转移过程中起重要作用。随着淋巴管内皮特异标记物和淋巴管生长因子的发现,肿瘤诱发淋巴管生成的分子机制和以抑制肿瘤淋巴管生成作为抗肿瘤转移靶点的研究引起临床关注。现将淋巴管生成于肿瘤淋巴道转移相关性的研究进展综述如下。     

结肠腺癌组织中Nup358的表达及意义

目的观察结肠腺癌组织中的核孔素358(Nup358)表达变化,探讨其表达与结肠腺癌临床病理特征之间的关系。方法结肠腺癌患者80例,行左半结肠切除术或右半结肠切除术,术中留取肿瘤组织、癌旁组织(距肿瘤组织5 cm以上的结肠组织)。采用免疫组化Envision染色法检测80例结肠腺癌组织及相应癌旁组织中的Nup358。结果 80例标本中,结肠腺癌组织中Nup358表达阳性56例(70.00%),癌旁组织中表达阳性10例(12.50%),两者相比,P<0.01。结肠腺癌组织中Nup358的表达与结肠癌浸润深度无关(P>0.05),与肿瘤分化程度及淋巴结转移相关,Nup358在低分化者中表达低于高中分化者,在有淋巴结转移者中表达高于无淋巴结转移者(P均<0.05)。结论结肠腺癌组织中Nup358的表达上调,并与结肠腺癌分化程度及淋巴结转移有关。     

大肠腺癌中nm23基因的低表达与淋巴结转移

目的研究肿瘤转移抑制基因ｎｍ２３表达产物二磷酸核苷激酶在大肠腺癌中的表达意义。方法应用ＬＳＡＢ免疫组织化学染色方法研究大肠腺癌标本７８例。结果ｎｍ２３基因在正常结肠粘膜腺体细胞为阳性表达。在大肠腺癌中呈现低表达，阴性率为７４％（５８／７８），其中全部细胞无表达３５例，部分细胞表达２３例。伴有淋巴结转移者其原发病灶表达阴性率为８５％（４０／４７），不伴有淋巴结转移者其阴性率为５８％（１８／３１），差异有显著意义（Ｐ＜００５）。ｎｍ２３基因表达与大肠腺癌的分化程度有关，高分化腺癌大多数呈现阳性表达，低分化腺癌呈现低表达。与临床分期无显著相关。结论ｎｍ２３基因在大肠腺癌的低表达与肿瘤的转移、浸润、分化程度有关     

结肠腺癌中叉头框蛋白M1表达及其与上皮型黏附蛋白的关系

目的检测叉头框蛋白(FOX)M1在结肠腺癌中的表达,探讨其与上皮型黏附蛋白(E-cadherin)的关系。方法结肠腺癌组(观察组)和正常结肠黏膜组(对照组)术后的标本,应用免疫组化方法检测两组中FOXM1和E-cadherin的表达,观察FOXM1和E-cadherin在不同临床特征中的表达差别,分析FOXM1和E-cadherin相关性。结果观察组中FOXM1表达的阳性率明显高于对照组,观察组中E-cadherin表达的阳性率明显低于对照组。观察组中FOXM1过表达、E-cadherin低表达均与淋巴结转移和微血管浸润密切相关。FOXM1过表达与肿瘤体积密切相关。线性相关分析显示观察组中FOXM1和E-cadherin表达呈负相关性。结论 FOXM1过表达可以促进结肠腺癌的发生和发展,FOXM1过表达可以在一定程度上下调E-cadherin的表达,对细胞间的黏附进行调节,促进肿瘤的进展。     

Livin、Caspase-3在结肠腺癌及结肠腺瘤组织中的表达及意义

目的探讨Livin、Caspase-3在结肠腺癌和结肠腺瘤组织中的表达及意义。方法应用免疫组织化学染色方法对89例结肠腺癌、50例结肠腺瘤和40例结肠正常黏膜组织(距癌边缘5 cm以外)进行Livin、Caspase-3检测。应用Western印迹检测方法对50例新鲜结肠腺癌、癌旁组织(距癌边缘5 cm以内)、结肠正常黏膜组织(距癌边缘5 cm以外)进行Livin、Caspase-3检测。结果结肠腺癌组织中Livin阳性率明显高于结肠腺瘤和结肠正常黏膜组织(P<0.05);结肠腺癌组织中Caspase-3阳性率明显低于结肠腺瘤和结肠正常黏膜组织(P<0.05);结肠腺瘤和结肠正常黏膜组织Livin、Caspase-3阳性率有显著性差异(P<0.05)。结论 Livin、Caspase-3在结肠腺癌的发生及发展上起一定作用。     

血小板内皮细胞黏附分子1在肺癌中表达及与转移的关系

目的探讨血小板内皮细胞黏附分子(PECAM)1在非小细胞肺癌(NSCLC)中表达及其与转移的关系。方法建立稳转PECAM1的A549细胞,加入抗PECAM1抗体抑制后,观察A549细胞生长。通过免疫组化方法检测105例NSCLC及10例肺良性病变的组织切片中PECAM1蛋白水平,分析PECAM1与患者肺癌的转移及愈后关系。结果加入抗PECAM1抗体,A549扩增抑制明显。NSCLC组织中,PECAM1表达阳性率明显高于肺良性病变组织(χ2=8.980,P=0.003)。PECAM1表达与肺癌患者淋巴结转移存在显著相关性(P=0.023)。PECAM1表达与患者无疾病生存期(PFS)及总生存期(OS)存在一定相关性(P=0.002,0.016)。结论在非小细胞肺癌中,PECAM1是患者肺癌转移及不良预后的生物学标志。     

人体结肠腺癌PKM2的表达及临床意义

目的 研究PKM2在人体结肠腺癌、腺瘤、炎性息肉及正常结肠黏膜中的表达及临床意义.方法 收集外科手术或结肠镜切除并经病理确诊的结肠腺癌、结肠腺瘤、结肠炎性息肉及正常结肠黏膜组织标本各30例,采用免疫组化方法检测其PKM2的表达.结果 PKM2在正常结肠黏膜组织、结肠炎性息肉、结肠腺瘤及结肠腺癌中的阳性表达率分别为0、6.67％、16.67％、80.00％,PKM2在结肠腺癌组织中的表达与正常结肠黏膜组织(x2=40.00)、结肠炎性息肉(x2=32.85)及结肠腺瘤(x2=24.09)中的表达差异有统计学意义(P ＜0.001).在结肠腺癌中,PKM2的表达水平与淋巴结转移(P=0.046) 、Dukes分期(P=0.013)有相关性,而与肿瘤分化程度(P=0.053/0.371)、浸润深度(P=0.084)无关.结论 PKM2在人体结肠腺癌的发生发展中有重要作用,对于结肠腺癌的早期诊断有一定指导意义.     

肺腺癌内皮抑素表达与微淋巴管密度及淋巴转移的关系

目的研究内皮抑素在肺腺癌中的表达及其与淋巴管生成和淋巴转移的关系。方法免疫组化法检测60例肺腺癌内皮抑素蛋白的表达及肺腺癌组织微淋巴管密度（MLVD）,分析内皮抑素表达与MLVD及淋巴结转移的关系。结果肺腺癌组织内皮抑素蛋白阳性率[61.7%（37/60）]高于癌旁正常组织[23.3%（14/60）]（P〈0.01）;其表达与肿瘤分期、淋巴结转移有关。内皮抑素阳性组MLVD（7.68±1.89）低于阴性组（9.17±1.95）（P〈0.01）,随内皮抑素表达程度加强,MLVD值减小。结论内皮抑素在抑制肺腺癌淋巴管生成及淋巴转移中可能起一定作用。     

结肠腺癌核仁素表达和Ki67标记的增殖指数的关系

目的检测结肠腺癌中核仁素(C23)表达和Ki67标记的增殖指数的关系,分析其临床意义。方法 65例结肠腺癌患者的临床资料及术后蜡块组织作为观察组,正常结肠黏膜组织25例作为对照组,采用免疫组化方法检测两组中C23和Ki67的表达。结果观察组中C23和Ki67的阳性率明显高于对照组(均P<0.001)。观察组中C23和Ki67表达与肿瘤最大径和浸润深度密切相关,C23表达与肿瘤分化程度密切相关。相关分析显示观察组中C23和Ki67呈正相关。结论结肠腺癌中C23和Ki67高表达可以促进肿瘤形成和进展,C23和Ki67有一定的协同作用。     

结肠腺癌中CyclinA表达与Ki67标记增殖的关系及意义

目的检测结肠腺癌中细胞周期素(Cyclin)A和Ki67的表达特征,分析二者在不同临床病理特中的表达意义,关注二者阳性率的相关性。方法结肠腺癌术后组织71例为观察组,距肿瘤边缘>5 cm的非肿瘤性结肠黏膜组织29例为对照组。应用免疫组化方法检测两组Cyclin A和Ki67的表达。结果观察组Cyclin A和Ki67表达阳性率明显高于对照组。观察组Cyclin A和Ki67表达与肿瘤最大径、浸润深度明显相关。Cyclin A表达与肿瘤脉管累犯相关。Cyclin A和Ki67均与肿瘤神经侵犯和淋巴结转移无明显相关性。相关分析显示观察组Cyclin A和Ki67表达呈正相关。结论结肠腺癌术后组织中Cyclin A和Ki67表达升高,二者呈正相关,对促进肿瘤形成和进展有一定价值。     

结肠癌淋巴管生成与转移的研究进展

远处转移是恶性肿瘤的重要生物学特征，也是肿瘤难以彻底根治的主要因素。淋巴道与血道转移是肿瘤最重要的两条转移途径，研究表明：大多数上皮起源的肿瘤以淋巴道转移为主，且发生较早。结肠癌是胃肠道中常见的恶性肿瘤之一，预后较差。在决定结肠癌预后的众多因素中，淋巴转移是其中重要的一个因素。在具备手术条件的患者中，淋巴结转移率达50％，淋巴结转移与预后的相关性高于原发灶的浸润程度，已成为决定结肠癌预后的重要的独立预后指标。因此对肿瘤淋巴管生成和淋巴转移机制的研究，已成为提高治疗结肠癌疗效的关键所在，是目前继肿瘤血管生成机制研究的又一热点。现就结肠癌淋巴管形成与转移的研究进展综述如下。     

淋巴管内皮透明质酸受体1对肺癌转移及预后评价的意义研究

目的检测肺癌患者血清淋巴管内皮透明质酸受体1(LYVE-1)水平,并探讨血清LYVE-1用于判断肺癌患者是否发生淋巴结转移及预测患者预后的临床意义。方法采用酶联免疫法(ELISA)检测57例肺癌患者血清中LYVE-1的水平,同时分析血清LYVE-1水平与患者临床病理特征的关系,通过受试者工作曲线(ROC)分析血清LYVE-1用于判断肺癌患者是否发生淋巴结转移的可行性,Kaplan-Meier法进行生存分析,评价LYVE-1用于预测病人预后的临床意义。结果肺癌患者血清LYVE-1为1625.0±343.0 pg/m L;血清LYVE-1与肺癌患者性别、肿瘤组织学分型、血清CEA和CA125无统计学差异(P0.05),而与TNM分期、淋巴结转移和远处转移情况有关(P0.05);血清LYVE-1用于诊断肺癌患者发生淋巴结转移的曲线下面积为0.728(95%CI:0.685-0.747,P0.05);LYVE-1的为1821 pg/m L时,其诊断的敏感性为79%,特异性为68%;血清LYVE-1大于1821pg/m L的肺癌患者预后要比血清LYVE-1小于1821 pg/m L的肺癌患者预后差,两组总生存时间有统计学差异(P=0.035)。结论血清LYVE-1可用于确定肺癌患者是否发生淋巴结转移,并可用于评估病人预后。     

血清SICAM-1、SVCAM-1表达与代谢综合征及其组分的关系

目的探讨血清可溶性细胞间黏附分子1（SICAM-1）和可溶性血管细胞黏附分子1（SVCAM-1）水平与代谢综合征（MS）及其组分的关系。方法将108名体检者按是否具有MS及其组分分组，并按具有MS组分的个数分组，采用酶联免疫吸附法检测血清SICAM-1和SVCAM-1水平，并与糖脂代谢指标及HOMA-IR作相关性分析。结果具有MS及其组分者SICAM-1、SVCAM-1水平分别较无MS及其组分者明显升高，而且随着MS组分数目增加，SICAM-1、SVCAM-1水平亦明显升高。结论SICAM-1、SVCAM-1均与糖脂代谢指标及HOMA—IR相关。MS组分的累积加重了血管内皮功能障碍，血管内皮功能障碍可能参与了MS的发生与发展。     

Higher CO2-insufflation pressure inhibits the expression of adhesion molecules and the invasion potential of colon cancer cells

AIM： To investigate the influence of CO2-insufflation pressure on adhesion, invasion and metastatic potential of colon cancer cells based on adhesion molecules expression. METHODS： With an/n vitro artificial pneumoperitoneum model, SW1116 human colon carcinoma cells were exposed to CO2-insufflation in 5 different pressure groups： 6 mmHg, 9 mmHg, 12 mmHg, 15 mmHg and control group, respectively for 1 h. Expression of E-cadherin, ICAM-I, CD44 and E-selectin was meas- ured at 0, 12, 24, 48 and 72 h after CO2-insufflation using flow cytometry. The adhesion and invasion capacity of SW1116 cells before and after exposure to CO2-insufflation was detected by cell adhesion/invasion assay in vitro. Each group of cells was injected intraperitoneally into 16 BALB/C mice. The number of visible abdominal cavity tumor nodules, visceral metas-tases and survival of the mice were recorded in each group. RESULTS： The expression of E-cadherin, ICAM-1, CD44 and E-selectin in SWl116 cells were changed significantly following exposure to CO2 insufflation at different pressures （P 〈 0.05）. The expression of E-cadherin, CD44 and ICAM-1 decreased with increasing CO2-insufflation pressure. The adhesive/ invasive cells also decreased gradually with increasing pressure as determined by the adhesion/invasion assay. In animal experiments, the number of abdominal cavity tumor nodules in the 15 mmHg group was also significantly lower than that in the 6 mmHg group （29.7± 9.91 vs 41.7±14.90, P = 0.046）. However, the survival in each group was not statistically different. CONCLUSION： CO2-insufflation induced a temporary change in the adhesion and invasion capacity of cancer cells in vitro. Higher CO2-insufflation pressure inhibited adhesion, invasion and metastatic potential in vitro and in vivo, which was associated with reduced expression of adhesion molecules.     

Invasion and metastasis of liver cancer: expression of intercellular adhesion molecule 1

To study the relationship between intercellular adhesion molecule 1 (ICAM-1) and liver cancer metastasis and to find predicting factors that could indicate the growth and metastasis of liver cancer. Methods: ICAM-1 expression in fresh tissue of normal liver and hepatocellular cancer (HCC) was examined by immunoperoxidase staining. Serum soluble intercellular adhesion molecule 1 (sICAM-1) from patients with a benign HCC tumor, and the expression of ICAM-1 in the orthotopically transplanted LCI-D20 tumor of a nude mouse liver cancer metastasis model, and in human hepatoma, the tumor surrounding tissue and normal liver, was analyzed semiquantitatively by the immuno-dot blot method. Tissue ICAM-1 expression (mRNA level) was detected by Northern blotting. Results: ICAM-1 expression in LD1-20 D metastatic liver cancer had a positive correlation with tumor size and the time after implantation. It increased suddenly as metastasis occurred being 3.03 ± 0.51 before metastasis and 8.24 ± 0.95 after metastasis, P < 0.01, then remained high, appending on the number of sites involved (monosite metastasis 5.48 ± 0.49, multisite metastasis 10.05 ± 1.17, P < 0.05). All six cases of normal liver samples were negative in anti-ICAM-1 immunohistochemical staining, 80.0% (36/45) of the HCC showed some ICAM-1 expression. The rate of positive cells was a little higher in large tumors, tumors with an intact capsule and tumors with metastasis, but there was no significant difference. It was noticed that two cancer emboli also had high ICAM-1 expression. The ICAM-1 concentration in HCC (13.43 ± 0.09) was higher than that in tumor surrounding the liver (5.89 ± 0.17, P < 0.01) and that in normal liver (4.27 ± 0.21, P < 0.01). sICAM-1, like tissue ICAM-1, was higher in HCC patients than in patients (with benign liver tumor and normal controls. Both tissue ICAM-1 and sICAM-1 were higher in the metastasis group than in the group without metastasis (tissue ICAM-1 20.24 ± 0.30 vs 10.23 ± 0.12 P < 0.05; sICAM-1 12.18 ± 0.25 vs 9.77 ± 0.54 P < 0.05). Northern blot analysis revealed that ICAM-1 expression, as indicated by mRNA level, was also higher in HCC and in cancer emboli than in tumor surrounding liver and normal liver. Conclusions: Tissue ICAM-1 and serum sICAM-1 could indicate the stage of HCC, and the potential of hepatoma cells for invasion and metastasis. They may play an important role in the metastasis cascade. Received: 20 January 1998 / Accepted: 25 June 1998     

An increase in the number of adhesion proteins with altered expression is associated with an increased risk of cancer death for colon carcinoma patients

Background and aims Reduced expression of components of the cell–cell adhesive cadherin–catenin complex has been related to the invasive phenotype in many malignancies, but the prognostic value of altered expression of its separate components varies in colon cancer. Our objective was evaluation of the cadherin–catenin complex, considered as a functional unit, in colon carcinomas and its relationship to patient outcome.Patients and methods Tumours from 206 patients operated for colon adenocarcinoma were analysed using immunohistochemistry of E-cadherin, , , and -catenins, and p120ctn. The sum of proteins with altered membranous expression was calculated as an overall adhesion score (ranging from 0 to 5) for each patient. The results were correlated with patient outcome.Results Of the tumours included in the analysis 0.5% had score 0, 4.9% had score 1, 13.6% had score 2, 31.6% had score 3, 33.0% had score 4, and 16.5% tumours had score 5. None of the proteins examined had individual, independent prognostic value. However, an increase in the number of proteins in the cadherin–catenin complex with altered expression was associated with an increased risk of cancer death (univariate P=0.002; multivariate P=0.007, HR 1.48, 95% CI 1.11–1.96).Conclusions An increase in the number of adhesion proteins with altered expression in the primary tumour is associated with increasingly impaired prognosis for patients operated for colon carcinoma. The results reveal that the entire cadherin–catenin complex should be evaluated when assessing its prognostic value in the disease.     

淋巴管内皮细胞透明质酸受体-1在胃癌组织中的表达及意义

目的:探讨淋巴管内皮细胞透明质酸受体-1(LYVE-1)在胃癌组织中的表达及临床意义．方法:采用组织芯片技术和免疫组化方法对85例胃癌组织和40例正常胃组织中LYVE-1的表达及淋巴管密度(LVD)进行检测．结果:LYVE-1的阳性产物表达于淋巴管内皮细胞胞质中,呈棕黄色染色．胃癌组织中LYVE-1阳性LVD显著高于正常胃组织(7．89±2．14 vs 1．15±1．62,P<0．01);瘤周的LYVE-1阳性LVD明显高于瘤内组织(9．28±1．18 vs 4．75±1．19,P<0．01);低分化(9．21±2．32)、Ⅲ-Ⅳ期(9．46±2．45)、有淋巴结转移(9．37±3．39)和远处转移(9．55±3．50)的胃癌组织中LYVE-1阳性LVD分别比高中分化(7．56±2．24)、Ⅰ-Ⅱ期(7．58±2．36)、无淋巴结转移(7．23±2．74)和远处转移(7．35±2．25)的明显增高(P<0．01, P<0．05)．结论:胃癌组织内及瘤周的LYVE-1阳性LVD明显增高,提示胃癌组织内的新生淋巴管主要位于瘤周,从而促进了肿瘤淋巴道转移．应用组织芯片大规模高效检测临床组织标本是可行的,具有快速、方便、经济、准确的特点．     

食管鳞癌组织中VEGF-D表达及其与淋巴管密度和淋巴转移的关系

目的 研究食管鳞状细胞癌(ESCC)组织中血管内皮细胞生长因子D(VEGF-D)的表达情况及其与淋巴管密度(LVD)的关系,并探讨其与食管癌淋巴结转移的关系.方法 免疫组化SABC法检测55例手术切除的食管鳞状细胞癌组织、癌旁组织、正常组织中淋巴管密度和VEGF-D的表达水平,对结果进行统计分析.结果 (1)食管癌组织...     

Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer

AIM： To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 （LYVE-1）, vascular endothelial growth factor receptor-3 （VEGFR-3） and CD44 genes and the relationship between their levels and clinicopathological parameters in gastric cancer.METHODS： Tissue samples were obtained from 33 patients （8 females） with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry. RESULTS： LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic fea- tures such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the dis- tribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining. CONCLUSION： LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.     

Relationship between serum ELAM-1 and metastasis among patients with colon cancer

PURPOSE: We studied serum ELAM-1 levels in colon cancer patients. METHODS AND RESULTS: Serum ELAM-1 levels were significantly higher in 52 patients with colon cancer (mean ± standard deviation, 69.3±28.6 U/ml) compared with 32 healthy volunteers (36.5±11.9 U/ml;P<0.001). The mean serum ELAM-1 level in patients with metastatic tumors was significantly greater than that of patients with nonmetastatic tumors. Sensitivity and specificity of serum ELAM-1 elevation in detecting metastasis was 75 and 87.5 percent, respectively. Those of carcinoembryonic antigen and carbohydrate antigen 19-9 elevations were 71.4 and 62.5 percent and 35.7 and 91.7 percent, respectively. Twenty-five (89.3 percent) of 28 metastatic tumors showed either serum ELAM-1 or carcinoembryonic antigen elevation. There were weak but significant correlations found between serum ELAM-1 and carcinoembryonic antigen or carbohydrate antigen 19-9 levels. Moreover, serum ELAM-1 increased before detecting the recurrency by imaging in five of seven recurrent colon cancer patients. CONCLUSION: These findings suggest that serum ELAM-1 could be a useful tumor marker for colon cancer, especially in synchronous and metaclonous metastasis.