鸟氨酸脱羧酶与食管鳞癌血管生成相关性的研究

目的 研究ODc mRNA和MVD在食管鳞癌中的表达及相关关系,探讨ODC在食管鳞癌血管生成中的可能作用及其与肿瘤浸润和转移的关系。方法 研究对象为41例经手术和病理证实的食管鳞癌患者,用RT-PCR方法测定癌组织和相应癌旁正常组织的ODC mRNA表达,以β-actin做内参照求得各自T/N值;用免疫组化方法测定癌组织和癌旁正常组织的MVD的T/N值。结果 在41例中,39例ODc mRNA的T/N值>1.0,占95.1％;40例MVD的T/N值>1.0,占97.6％。ODC mRNA和MVD与食管鳞癌的肿瘤大小、浸润深度和淋巴结转移有关,ODC mRNA与肿瘤分化程度有关。ODC mRNA的T/N值与MVD的T/N值正相关。结论 ODC与食管鳞癌血管生成和肿瘤浸润转移密切相关。ODC可能是通过影响血管生成而促进食管鳞癌的浸润和转移。     

5-脂氧合酶mRNA在食管鳞癌中的表达及与血管生成的关系

目的探讨5-脂氧合酶（5-LOX）和微血管密度（MVD）在食管鳞状上皮细胞癌（ESCC）组织中的表达及相关关系，及5-LOX与肿瘤浸润和转移的关系。方法用半定量RT-PCR法测定35例ESCC患者癌组织（T）和相邻癌旁组织（N）中5-LOX mRNA的表达，求得T／N值。同时用免疫组织化学法测定癌组织和癌旁正常组织中微血管密度（MVD）的T／N值。结果在35例ESCC患者中，33例5-LOX mRNA的T／N值〉1．0，占94．3％，34例MVD的T／N值〉1．0，占97．1％。5-LOX mRNA和MVD与食管鳞癌的肿瘤大小、浸润深度和淋巴结转移、肿瘤分化程度有关。5-LOX mRNA的T／N值与MVD的T／N值呈正相关。结论5-LOX与食管鳞癌血管生成和肿瘤浸润转移密切相关，其高表达可能促进肿瘤血管生成，从而促进ESCC的浸润和转移。     

内皮抑素在食管鳞癌中的表达及其意义

目的研究内皮抑素在食管鳞癌中的表达及其意义。方法采用免疫组化SP法检测内皮抑素在62例食管鳞癌中的表达。结果食管鳞癌组织内皮抑素阳性表达率高于切缘组织和食管良性病组织（P〈0．01），食管鳞癌内皮抑素表达水平与原发肿瘤的浸润深度、远处转移情况、细胞分化程度、临床TNM分期均有密切关系（P均〈0．05），而与原发肿瘤部位、区域淋巴结转移状况以及食管鳞癌患者的年龄、性别、饮食习惯、家族史等均无明显关系（均P〉0．05）。结论内皮抑素可能在抑制食管鳞癌侵袭和转移过程中发挥重要作用，可以作为判断其预后的指标之一。     

食管鳞癌组织中NF-κB p65、VEGF的表达及其与血管密度测定的意义

采用免疫组化S-P法检测61例食管鳞癌患者组织中核转录因子-κB（NF-κB）p65和血管内皮生长因子（VEGF）的表达及CD105标记的肿瘤内徽血管密度（MVD）。结果NF-κB p65表达与食管鳞癌的组织学分级、浸润深度和淋巴结转移均呈正相关（P均〈0．01），VEGF蛋白表达及MVD与食管鳞癌组织学分级和浸润深度均无关，但与淋巴结转移呈正相关（P〈0．05）；NF-κB p65与VEGF表达呈正相关（P〈0．01）；二者均与MVD呈正相关（P均〈0．05）。提示NF-κB p65参与食管鳞癌的发生、发展，其机制可能与VEGF的表达和肿瘤血管生成有关。     

食管鳞癌中Paxillin mRNA的表达及其与癌转移的关系

目的探讨Paxillin mRNA表达与食管癌转移的关系。方法采用原位杂交方法检测54例食管鳞癌、癌旁不典型增生组织及其正常食管组织中Paxillin mRNA的表达。结果有淋巴结转移的21例（A组）食管鳞癌组织、癌旁不典型增生组织和正常食管组织中Paxillin mRNA阳性表达率分别为90．48%（19／21）、52．38％（11／21）和0，无淋巴结转移的33例（B组）食管鳞癌组织、癌旁组织和正常食管组织中的Paxillin mRNA阳性表达率分别为33．33％（7／33）、23．80％（5／33）和0。两组癌组织、癌旁不典型增生组织中Paxillin mRNA阳性表达率比较，P均〈0．05。结论Paxillin mRNA表达与食管鳞癌的转移密切相关。     

畸胎瘤细胞源性生长因子和血管内皮生长因子在食管鳞癌中的表达及临床意义

目的 探讨食管鳞癌(ESCC)中畸胎瘤细胞源性生长因子(PCDGF)、血管内皮生长因子(VEGF)的表达与肿瘤临床病理参数之间的关系,明确PCDGF和VEGF在血管生成中的作用.方法 以免疫组化方法检测郑州大学第一附属医院2005年7月至2006年5 月收治的50例食管鳞癌患者手术切除标本PCDGF与VEGF的表达,并以CD105抗体标记肿瘤组织血管内皮细胞,计算肿瘤间质微血管密度(MVD).结果 食管鳞癌中PCDGF、VEGF的表达较正常食管上皮明显增加(P＜0.01);PCDGF和VEGF与肿瘤的浸润深度、TNM分期和淋巴结转移呈正相关(P均＜0.05);PCDGF、VEGF的表达与MVD值呈显著正相关(P＜0.01);PCDGF的表达与VEGF的表达呈正相关(P＜0.05).结论 PCDGF标记癌组织的敏感性较高,有望成为一种新的食管鳞癌肿瘤标志物.食管鳞癌中PCDGF、VEGF的表达与血管生成关系密切,可能通过促进肿瘤新生血管生成参与肿瘤的生长、浸润和转移.     

食管鳞癌组织中MICA基因mRNA、蛋白表达及意义

目的探讨MHCⅠ类链相关蛋白A（MICA）与食管鳞癌分化程度及淋巴结转移的相关性。方法采用RT-PCR法检测43例食管鳞癌组织（鳞癌组）和相应癌旁正常组织（癌旁组）中MICA mRNA表达,免疫组化SP法检测两组MICA蛋白表达,Spearman相关关系检验分析其相关性：结果鳞癌组MICA mRNA的表达水平显著高于癌旁组（t=8．35,P〈0．05）。鳞癌组MICA蛋白表达与癌组织分化程度及淋巴结转移有相关性,与肿瘤大小、性别、年龄无相关性（P〉0．05）;MICA蛋白表达水平与MICA mRNA表达水平呈显著正相关（rs=0．905,P〈0．01）。结论MICA高表达与食管鳞癌组织分化程度密切相关,可能在食管鳞癌的发生发展、浸润转移过程中起重要作用。     

PTEN在食管癌中的表达及其与微血管密度和临床病理特征的关系

目的:探讨抑癌基因PTEN在食管癌及癌旁正常组织中的表达, 及其与微血管密度(MVD)和临床病理特征的关系.方法:选用食管鳞癌手术切除病理标本48例,手术远端正常食管组织标本40例. 采用免疫组织化学SP法检测PTEN编码蛋白的表达水平,CD31抗体进行血管内皮染色、计算微血管密度, 分析PTEN在不同组织中的表达与MVD和食管癌组织分化程度、浸润深度、淋巴结转移的关系.结果:食管鳞癌组织中PTEN编码蛋白阳性表达率低于癌旁正常食管黏膜组织(52.08%vs 92.50%, P<0.01), 而其MVD值显著高于癌旁正常组织(41.72±8.67 vs 21.01±3.85, P<0.01); Ⅰ、Ⅱ、Ⅲ级鳞癌PTEN阳性表达率有显著差异(75.0% vs 55.0% vs 33.33%, 均P<0.05), MVD值差异无统计学意义; 癌组织侵及浅肌层以上与深肌层PTEN与MVD值的表达有显著差异(77.27% vs 42.31%; 35.49±5.89vs 46.01±6.27, 均P<0.01); 淋巴结转移组与非转移组PTEN阳性表达率无显著差异, MVD值差异则有统计学意义(46.71±7.89 vs 35.92±2.54, P<0.01).结论:抑癌基因PTEN、MVD在食管癌中表达的高低, 与肿瘤的生长、浸润和转移相关.PTEN基因表达的突变或缺失能促进肿瘤血管的形成, 可作为临床治疗和判断预后的依据.     

食管鳞癌组织中E—cadherin、VEGF的表达变化及意义

目的观察食管鳞癌组织中上皮性钙黏附蛋白（E—cadherin）和血管内皮生长因子（VEGF）的表达变化,并探讨其临床意义。方法采用免疫组化sP法检测60例食管鳞癌组织和癌旁正常组织中的E-cadherin、VEGF。结果食管鳞癌组织中E—cadherin表达阳性34例（56．6％）、VEGF表达阳性42例（70．0％）,癌旁正常组织中分别为55例（91．6％）、24例（40．0％）,两组比较,P均〈0．05。E-cadherin、VEGF表达与食管鳞癌临床分期、肿瘤浸润深度及淋巴结转移有关（P均〈0．05）。结论食管鳞癌组织中E—cadherin表达降低,VEGF表达升高;二者与食管鳞癌的浸润、转移有密切关系。     

Ang-2在食管鳞癌血管生成中的作用

应用免疫组化SP法检测食管鳞癌及食管断端正常鳞状上皮中促血管生成素（Ang）-2、血管内皮生长因子（VEGF）的表达，以及CD105标记的微血管密度（MVD）。结果显示，Ang-2蛋白表达主要定位于肿瘤细胞的胞质和胞膜，尤其是癌灶边缘血管重建区。食管鳞癌组织中Ang-2和VEGF蛋白表达显著高于食管断端正常鳞状上皮（P〈0．01），癌组织中Ang-2表达程度与VEGF表达程度及MVD呈明显正相关（P〈0．01，〈0．05）。提示食管鳞癌组织中Ang-2高水平表达可能促进肿瘤新生血管形成．促进食管鳞癌的发生发展。     

Expression of vascular endothelial growth factor-C and angiogenesis in esophageal squamous cell carcinoma

AIM: To investigate the expression of vascular endothelial growth factor-c (VEGF-C) mRNA and microvessel density (MVD) in human esophageal squamous cell carcinoma (ESCC) and its relationship with clinical significance. METHODS: Specimens obtained from 43 patients undergoing surgical resection for ESCC were used in this study. The expression of VEGF-C mRNA was examined by in situ hybridization. Tumor MVD was determined immunohistochemically with anti-CD31 antibody and estimated by image analysis. Ten sections of adjacent normal mucosa were also examined. RESULTS: VEGF-C mRNA expression was detected in cytoplasm of carcinoma cells. Of the 43 ESCC patients studied, 18 cases (41.9%) were positive for VEGF-C mRNA. No VEGF-C mRNA expression was observed in normal esophageal mucosa. VEGF-C mRNA expression correlated significantly with lymph node metastasis, TNM stage and depth of invasion (P < 0.05). Furthermore, histological grade (differentiation) tended to correlate with VEGF-C mRNA expression, but was not statistically significant (P > 0.05). In tumor lesions, the MVD was significantly greater than that in normal esophageal mucosa. MVD correlated significantly with lymph node metastasis, TNM stage and depth of invasion (P < 0.05), but not with histological grade (differentiation) (P > 0.05). Lesions with VEGF-C mRNA expression had a significantly higher MVD than that of those without VEGF-C mRNA expression (P < 0.05). CONCLUSION: VEGF-C plays a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in ESCC. VEGF-C is one of the important predictors of the biological behavior in ESCC.     

Correlative studies on bFGF mRNA and MMP-9 mRNA expressions with microvascular density, progression, and prognosis of gastric carcinomas

AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD),invasion, metastasis, and prognosis. METHODS: In situ hybridization and immunohistochemical techniques were used to detect the expressions of bFGFmRNA and MMP-9mRNA and the proteins of CD34 in 105 specimens of gastric carcinomas. RESULTS: In situ hybridization study showed that positive rates of bFGF mRNA and MMP-9mRNA expressions were 60.95% and 59.19%; the mean MVD was 46.09±11.52 and 43.75±13.41, respectively in piece/0.72 mm2 in tumors with bFGFmRNA and MMP-9mRNA positive expressions, which were significantly higher than those with negative expression (29.41±12.47; 33.45±13.92 piece/0.72 mm2, respectively). The positive expression rates of bFGFmRNA and MMP-9mRNA were correlated to the tumor invasion depth (rs= 0.211, P= 0.031; rs= 0.335, P= 0.001), growing pattern (rs= 0.324, P= 0.001; rs= 0.267, P= 0.006), vessel invasion (rs= 0.579, P= 0.001; rs = 0.209, P= 0.032), lymph node metastasis (rs= 0.405, P= 0.001; rs= 0.343, P= 0.001) and distant metastasis (rs= 0.474, P= 0.001; rs = 0.468, P = 0.001), but not correlated to tumor type (rs=0.134,P=0.173;rs=0.103,P=0.145) and differentiations (rs=0.096,P= 0.332;rs=0.102,P=0.298). The mean MVD was much higher in the tumors with infiltrating growth at stage T3-T4, with vessel invasion, lymph node metastasis and distant metastasis than those with expanding growth type (t = 10.105, P= 0.001) at stage T1-T2 (t=5.961,P=0.001),with non-vessel invasion (t=7.394,P=0.001),non-lymph node metastasis (t = 3.819, P= 0.01) and non-distant metastasis (t = 10.578, P= 0.001). Positive correlation was observed between MVD and the expressions of bFGFmRNA and MMP-9mRNA (t = 3.207, P=0.002; t = 7.035, P= 0.001, respectively). The mean survival time and 5-year survival rate were lower in cases with MVD over 39.5 and the positive expressions of bFGFmRNA and MMP-9mRNA than those with MVD less than 39.5 and the negative expressions of bFGFmRNA and MMP-9mRNA. CONCLUSION: bFGF and MMP-9 promote the angiogenesis of the gastric cancers. Detection of the expressions of bFGF and MMP-9 can serve as a useful index to determine the angiogenesis, invasion, metastasis, and prognosis of gastric cancers.     

Clinicopathological significance of heparanase and basic fibroblast growth factor expression in human esophageal cancer

AIM: Human heparanase is an endo-D-glucuronidase that degrades heparan sulfate/heparin and has been implicated in a variety of biological processes. The objective was to investigate the expression of heparanase (Hps) and basic fibroblast growth factor (bFGF) and their relationship to neoangiogenesis and metastasis of human esophageal carcinoma. METHODS: Seventy-nine patients who had undergone esophageal resection for esophageal carcinoma without preoperative treatment were included in the present study. Immunohistochemistry was used to study the expression of Hps, bFGF and microvessel density (MVD) in 79 cases of esoph-ageal carcinoma. bFGF and Hps were quantitatively detected with immunohistochemistry in 79 cases of human esopha-geal carcinoma and 19 cases of adjacent normal human esophageal carcinoma. Cd34 was used to explore the MVD as a marker of endothelial cells. RESULTS: Hps and bFGF expression in tumor tissue, being remarkably higher than that in normal esophageal tissue, were significantly correlated with clinicopathological features (depth of invasion, lymph-node metastasis and TNM stage) and MVD. CONCLUSION: The results of this study suggest that the coexpression of Hps and bFGF plays a key role in angiogenesis, invasion and metastasis of esophageal carcinoma. Hps and bFGF may serve as a predictor of progression in esophageal carcinoma. The expression of heparanase in esophageal carcinoma enhances growth, invasion, and angiogenesis of the tumor, and bFGF seems to be a potent antigenic factor for esophageal carcinoma.     

基质金属蛋白酶-9和组织金属蛋白酶抑制剂-1在食管鳞癌中的表达

目的探讨基质金属蛋白酶-9（MMP-9）和组织金属蛋白酶抑制剂-1（TIMP-1）在食管鳞癌中的表达及其临床意义。方法用免疫组化和Western blot法分别检测41例食管鳞癌患者的癌及相应正常组织中MMP-9和TIMP-1的表达变化。结果食管鳞癌组织中MMP-9阳性表达率与食管癌淋巴结及静脉转移有关；MMP-9的阳性表达率与表达量均显著高于TIMP-1；MMP-9和TIMP-1的表达呈负相关。结论MMP-9与食管鳞癌的侵袭转移有关，其机制可能与食管鳞癌组织中的MMP-9／TIMP-1平衡失调有关；MMP-9与TIMP-1联合检测有助于食管鳞癌生物学行为的判断。