胃癌及癌前病变中的TFF-1、EGFR表达与血管再生的相关性研究

目的 探讨胃癌及癌前病变中三叶因子-1(trefoil factorl,TFF-1)、表皮生长因子受体(epidermal growthfactor receptor,EGFR)与血管形成的关系.方法 将121例患者存档标本分为萎缩性胃炎伴肠化生、不典型增生、高分化胃癌和低分化胃癌4组,另取29例体检正常人标本作为正常组.采用免疫组化SP方法测定TFF-1、EGFR值;同时所有对象用抗CD 34血管标记物表达测微血管密度(microvessel density,MDV)值,并进行相关性分析.结果 在正常对照组及萎缩性胃炎伴肠化生、不典型增生、高分化胃癌和低分化胃癌各组中,TFF-1阳性表达率分别为100.0%、85.18%、81.82%、64.00%、38.39%,呈逐渐减弱趋势.后4组与正常组比较有显著差异,高分化胃癌组表达高于低分化胃癌组(P<0.05);而EGFR在正常组、萎缩性胃炎伴肠化生、不典型增生、高分化胃癌和低分化胃癌组中的表达分别为24.13%、40.74%、42.42%、56.00%、72.22%,呈逐渐增加趋势.后4组与正常组比较有显著差异,高分化胃癌组表达低于低分胃癌组(P<0.05).结论 实验结果显示TFF-1与EGFR呈负相关(r=-0.913,P<0.01).EGFR值与MDV呈正相关(r=0.936,P<0.01).TFF-1与EGFR在胃癌的早期诊断中起重要作用,可以作为判断肿瘤转移与否及手术前肿瘤是否复发的评判标准.     

胃癌组织PTEN、VEGF和MVD的表达及意义

目的观察胃癌组织中第10染色体缺失与张力蛋白同源的磷酸酶基因(PTEN)、血管内皮生长因子(VEGF)、微血管密度(M VD)表达,探讨其与胃癌生物学行为的关系。方法用免疫组化法检测60例胃癌标本中PTEN、VEGF、M VD的表达,分析各指标与胃癌临床病理学特征的关系。结果①胃癌组织中PTEN的阳性表达率为46.7%,VEGF为66.6%,M VD为(64±26)条/HP;PTEN的表达与患者的术后生存时间呈正相关(r=0.556,P<0.01),与肿瘤大小、分型、淋巴结转移、分期有关(P均<0.05),与VEGF的表达无相关性(r=-0.136,P>0.05);VEGF和PTEN对胃癌患者预后有不同的影响。②VEGF和M VD的表达与胃癌的大小、分型、分化程度、浸润深度、淋巴结转移、分期有关(P均<0.05);与患者的术后生存时间呈负相关(r=-0.398,P<0.05)。结论PTEN、VEGF、M VD的表达与胃癌生物学行为及预后有密切关系。     

肾上腺皮质肿瘤VEGF、TSP-1的表达及其与微血管密度的关系

目的 研究血管内皮生长因子(VEGF)、血小板反应素1(TSP-1)在肾上腺皮质肿瘤中的表达及其与微血管密度(MVD)的关系.方法 采用免疫组化方法检测13例肾上腺皮质癌、30例肾上腺皮质腺瘤和7例正常肾上腺组织中VEGF、TSP-1及MVD(以CD34为标记)的表达.结果 肾上腺皮质癌VEGF表达高于肾上腺皮质腺瘤,差异有统计学意义(P＜0.01);TSP-1在正常肾上腺皮质表达明显高于肾上腺皮质癌(P＜0.01);MVD在肾上腺皮质癌为(107.67±11.91)/视野,显著高于肾上腺皮质腺瘤(59.46±21.31)/视野和正常肾上腺皮质组织(25.10±3.94)/视野(均P＜0.01);VEGF的表达与MVD呈正相关(P＜0.01),TSP-1的表达与MVD呈负相关(P＜0.01),VEGF与TSP-1的表达呈负相关(P＜0.01).结论 VEGF和TSP-1在肾上腺皮质肿瘤的表达失衡是其肿瘤血管异常生成的重要原因.     

肺腺癌VEGF-C的表达与MVD、MLVD及淋巴转移的关系

目的 探讨肺腺癌血管内皮生长因子-C(VEGF-C)表达与微淋巴管密度(MLVD)、微血管密度(MVD)及淋巴转移之间的关系.方法 RT-PCR法检测36例肺腺癌组织中VEGF-C mRNA的表达,并以免疫组化法检测肺癌组织VEGF-C蛋白的表达、MLVD及MVD.结果 VEGF-C mRNA在肺腺癌组织中的表达比正常肺组织相对较高(P<0.01).VEGF-C蛋白表达在肿瘤周边部位显著高于肿瘤中心部位(P=0.015);其表达与肿瘤分化程度无关,与肿瘤的TNM分期有关,Ⅲ～Ⅳ期显著高于Ⅰ～Ⅱ期(P=0.026).在VEGF-C蛋白阳性组,MVD高于阴性组(P=0.020),MLVD显著高于阴性组(P=0.008),淋巴结转移增多(P=0.039).结论 VEGF- C mRNA在肺腺癌组织中高表达,VEGF-C蛋白表达与肺腺癌血管生成及淋巴管生成和淋巴结转移关系密切.     

乳腺癌组织中HIF-1α、VEGF、MVD的表达及意义

目的检测乳腺癌组织中缺氧诱导因子（HIF）-1α、血管内皮生长因子（VEGF）及微血管密度（MVD）,并探讨其临床意义。方法采用免疫组织化学SP法检测乳腺纤维腺瘤、癌旁正常乳腺组织和乳腺癌组织中的HIF-1α、VEGF及MVD。结果乳腺纤维腺瘤、癌旁正常乳腺组织中几乎无HIF-1α、VEGF表达,乳腺癌组织中HIF-1α阳性率为62．22％。HIF-1α表达与淋巴结转移、雌激素受体状态及临床分期相关（P〈0．05）,与VEGF、CD34表达之间存在显著相关性。HIF-1α、VEGF的过表达及高MVD与乳腺癌的不良发展有关。结论乳腺癌组织中HIF-1α、VEGF表达上调,两者可能成为预测断乳腺癌侵袭、转移及预后的重要指标。     

术前化疗对食管鳞癌HIF-1α、VEGF和MVD表达的影响及意义

目的 观察术前化疗对食管鳞癌缺氧诱导因子(HIF)-1α、血管生长因子(VEGF)和微血管密度(MVD)的影响及意义.方法 用免疫组织化学SP法检测25例经术前化疗的食管癌标本(术前化疗组)和30例单纯手术的同期别的食管癌标本(手术组)中HIF-1α、VEGF、MVD.结果 术前化疗组、对照组HIF-1α的表达分别为32.0%(8/25)、63.3%(19/30),VEGF阳性表达率分别为36.0%(9/25)、66.7%(20/30),MVD分别为33.78±2.06、36.44±5.64,两组相比P均<0.05.术前化疗病理有效者19例,HIF-1α的阳性表达率为31.6%(6/19),VEGF的阳性表达率36.8%(7/19),MVD 33.46±3.12,与对照组较比P均<0.05,而病理无效者6例与对照组比较P均>0.05.结论 术前化疗能显著下调HIF-1α和VEGF的表达,并通下调VEGF抑制肿瘤微血管的生成;抗血管生成是化疗的又一重要的抗肿瘤机制.     

胃癌淋巴结转移与VEGF—D、VEGFR-3、LVD的关系

目的探讨胃癌淋巴结转移与血管内皮生长因子D（VEGF—D）、血管内皮生长因子受体3（VEGFR-3）、淋巴管密度（LVD）表达间的关系。方法对59例胃癌术后标本采用免疫组织化学sP法检测VEGF—D表达,用VEGFR-3抗体免疫组织化学sP法标记淋巴管,检测肿瘤组织及正常组织LVD。结果VEGF—D、VEGFR-3在癌组织中表达率分别为59．32％、67．80％,明显高于癌旁不典型增生组织及正常胃黏膜组织（P〈0．05）。癌周组织的LVD表达为（21．29±8．21）,明显高于周边正常组织（P〈0．05）。VEGF—D表达阳性组35例与阴性组24例的LVD分别为（23．15±7．58）和（11．93±5．31）,其差异具有统计学意义（P〈0．05）。VEGF—D、LVD在癌组织中的表达与淋巴结直径、淋巴结分期、浸润深度、TNM分期及分化程度有关（P〈0．05）。结论VEGF．D在胃癌组织中高表达,并与肿瘤的淋巴管形成及淋巴结转移密切相关。     

大肠癌组织中VEGF-C、HGF、MVD的表达变化及意义

目的观察大肠癌组织中血管内皮生长因子（VEGF）-C、肝细胞生长因子（HGF）、微血管密度（MVD）的表达变化,并探讨其意义。方法采用免疫组化SP法检测48例大肠癌和9例正常大肠组织中的VEGF-C、HGF蛋白;用CD34标记微血管,计算MVD。结果大肠癌组织中VEGF-C、HGF蛋白的阳性表达率高于正常大肠组织（P均〈0.05）,两者的表达呈正相关（r=0.529,P〈0.05）;大肠癌组织中MVD值高于正常大肠组织（P〈0.05）;VEGF-C、HGF阳性表达及MVD升高与大肠癌Dukes分期和淋巴结转移相关（P均〈0.05）;VEGF-C、HGF阳性大肠癌的MVD值高于VEGF-C、HGF阴性者（P均〈0.05）。结论大肠癌组织中VEGF-C、HGF蛋白高表达并MVD增加,VEGF-C和HGF与大肠癌的浸润、转移有关,可能通过参与大肠癌微血管的生成过程。     

胃癌血管内皮生长因子与微血管密度的关系

血管生成与肿瘤的生长密切相关。最近的一些研究报道指出，血管内皮生长因子（ＶＥＧＦ）是一种重要的促肿瘤血管生长因子［１］，ＦⅧ因子是血管内皮的特异标记物。我们用ＶＥＧＦ和ＦⅧ因子染色的免疫组化技术，观察了胃癌组织不同区域ＶＥＧＦ阳性表达和微血管密度（Ｍ...     

喉癌组织中COX-2、VEGF、MVD的表达及意义

采用免疫组化法检测50例喉癌组织中诱导型环氧合酶（COX-2）、血管内皮生长因子（VEGF）的表达，用CD34。标记新生血管内皮细胞，观察微血管密度（MVD）。喉癌组织中COX-2、VEGF的阳性表达率分别为62％和68％，MVD为（51．62±16．64）条／200倍视野。COX-2和VEGF的表达与喉癌病理学分级及临床分期有关。表明喉癌组织中COX-2呈高表达，COX-2与肿瘤新生血管形成有关，检测癌组织中COX-2、VEGF有助于喉癌的绢织学分级和预后判断。     

血管内皮生长因子的表达与胃癌浸润和转移的关系

目的　研究血管内皮生长因子165(VEGF)mRNA在胃癌中的表达 ,探讨VEGF与胃癌浸润和转移的关系。方法　采用RT PCR方法 ,对 31例胃癌及非癌组织手术标本中VEGF165mRNA的表达进行相对定量研究。结果　胃癌组织中VEGF165mRNA表达的平均相对量 (1.12 5± 0 .35 6 )明显高于非癌组织的表达量 (0 .76 0± 0 .2 78,P <0 .0 5 ) ,其中淋巴结转移组 (1.2 19± 0 .377)和Ⅲ、Ⅳ期组 (1.2 6 2±0 .386 )分别高于无淋巴结转移组 (0 .92 7± 0 .2 0 5 )和Ⅰ、Ⅱ期组 (0 .934± 0 .194 ,P均 <0 .0 5 )。VEGF高表达者中淋巴结转移率为 83.3% ,Ⅲ和Ⅳ期占 77.8% ,均明显高于VEGF低表达者的 4 6 .2 %和 33.8%(P <0 .0 5 )。结论　胃癌组织中有VEGF的高表达 ,VEGF的表达在胃癌浸润和转移过程中发挥重要作用。     

EMMPRIN、HER-2蛋白表达与胃癌侵袭转移的关系

目的: 探讨细胞外基质金属蛋白酶诱导因子(EMMPRIN)、人表皮生长因子受体2(HER-2/neu)蛋白表达与人胃癌侵袭转移的关系, 以及2种蛋白表达之间的关系.方法: 应用量子点免疫荧光组织化学技术检测人胃癌组织芯片150芯(包括70例胃癌组织和5例正常胃黏膜组织)中EMMPRIN和HER2的蛋白表达, 并分析他们与临床病理特征的相关性.结果: 胃癌和正常胃黏膜组织中的EMMPRIN阳性表达率分别为72.86%和20.00%, 差异有显著性( P = 0.029). 在胃癌组织中HER-2蛋白的阳性率为47.14%(33/70), 高于正常胃黏膜组织, 但差异无显著性( P = 0.063).EMMPRIN、HER-2蛋白表达与胃癌患者年龄、性别、分化程度、肿瘤的浸润深度以及临床TNM分期之间差异均无显著性( P>0.05),仅与淋巴结转移显著相关( P<0.05). 在70例胃癌组织中EMMPRIN与HER-2蛋白表达之间呈显著正相关( r = 0.383, P = 0.001).结论: EMMPRIN与HER-2/neu可能协同促进了胃癌的淋巴结转移.     

Imbalance between expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in invasiveness and metastasis of human gastric carcinoma

AIM: The expressive balance between matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a critical role in maintaining the degradation and synthesis of extracellular matrix. Loss of such balance is associated with invasion and metastasis of tumors. This study aimed to determine the expression of MMP-9 and TIMP-1 in gastric carcinoma, and the association of the expressive imbalance between MMP9 and TIMP-1 with the invasion and metastasis and prognosis of gastric carcinoma.METHODS: We used immunohistochemistry to determine the expressions of MMP-9, TTMP-1 and proliferating cell nuclear antigen Ki-67 in the gastric specimens taken from 256 patients with primary gastric carcinoma. The patients were followed-up for up to 96 months.RESULTS: No association between the expression of MMP9 and TIMP-1 and patients' sex and age, tumor size and location of gastric carcinoma was observed. The incidence of the positive expression of MMP-9 in cases with tumors invasion to muscularis propria and visceral peritoneum (70.13% and 69.09%, respectively) was significantly higher than that in cases with tumor invasion only to lamina propria or submucosa (42.50 %, P=0.0162). The positive correlation between MMP-9 expression and the depth of tumor invasion was observed (Pearson correlation coefficient=0.2129,P=0.016). Along with the increase of the metastatic station of lymph nodes, the incidence of the MMP-9 expression was increased by degrees; a positive correlation between them was observed (Pearson correlation coefficient=0.2910,P=0.0001). There was also a significant correlation between MMP-9 expression and the TNM stage in gastric carcinoma (Pearson correlation coefficient=0.3027, P＜0.0001). The incidence of MMP-9 expression in stage Ⅱ and Ⅲ/Ⅳ (75.00%and 76.15%, respectively) was significantly higher than those in stage Ⅰ (46.15 %, P＜0.0001). A negative correlation between TIMP-1 immunoreactivity and the depth of invasion,status of lymph node metastasis and TNM stage was observed (Pearson correlation coefficient =-0.1688, -0.3556and -0.3004, P=0.023, ＜0.0001 and ＜0.0001, respectively).Four types of co-expression of MMP-9 and TIMP-1 were observed; i.e. MMP-9 positive but T IMP-1 negative (n=115),both positive (n=52), both negative (n=62) and MMP-9negative but TIMP-1 positive (n=27). The frequency of serosal invasiveness was significant higher in patients with MMP-9 but without TIMP-1 expression than those with other types of the co-expression (P=0.0303). The incidence of lymph node metastasis was highest in patients with MMP-9but without TIMP-1 expression, and lowest in those with TIMP-1 but without MMP-9 expression (P＜0.0001). The survival rate in patients with MMP-9 but without TIMP-1expression was lower than that in those with TIMP-1 but without MMP-9 expression (P=0.0014).CONCLUSION: Our results in gastric carcinoma demonstrated a significant positive association of MMP-9 over-expression with proliferation of tumor cells, the depth of invasiveness,lymph node metastasis and TNM stage, suggesting MMP-9can serve as a molecular marker of tumor invasion and metastasis. We also demonstrate a significant negative relationship of TIMP-1 expression with the depth of invasiveness and lymph node metastasis, which provide a new idea in the tumor biological and genetic treatment.The interaction between MMP-9 and TIMP-1 in the processes of tumor invasion and metastasis is that MMP-9 mainly promotes tumor invasion and metastasis and TIMP-1 inhibits functions of MMP-9. The imbalance between MMP-9 and TIMP-1 expression may suggest the occurrence of tumor invasion and metastasis, predict poor prognosis. For patients with imbalanced MMP-9 and TIMP-1 expression, the optimal treatment scheme needs to be selected.     

Hpa和nm23在大肠癌的表达及其与侵袭转移的相关性

目的 探讨乙酰肝素酶Hpa及转移抑制基因nm23在大肠癌组织中的表达及其与临床病理特征的关系.方法 采用免疫组化EnVision法检测54例原发性大肠癌组织中Hpa及nm23蛋白的表达.结果 Hpa和nm23蛋白在大肠癌中的阳性表达率分别为48.1%、63.0%;nm23和大肠癌肿瘤大小无明显相关(P>0.05),而Hpa与肿瘤大小显著相关(P<0.01),nm23和Hpa蛋白与肿瘤浸润深度、淋巴结转移和肝转移有关(P<0.05,P<0.01);Hpa与nm23表达之间无明显相关性.结论 Hpa和nm23的表达与大肠癌的浸润转移密切相关.检测大肠癌组织中Hpa和nm23的表达水平对判断患者的预后和肝转移具有一定的参考价值.     

肾癌组织中MMP-7表达和MVD测定及其临床意义

目的 探讨基质溶解素(MMP-7)及微血管密度(MVD)在肾癌肿瘤浸润转移中的作用.方法 应用免疫组织化学SP法检测肾癌组织(163例)、正常肾组织(101例)中MMP-7表达和MVD,并分析其与肾癌临床病理参数的相关性.结果 肾癌组织中MMP-7表达及MVD均显著高于正常肾组织(P<0.05),且两者呈显著正相关(r=0.341,P<0.01);MMP-7表达和MVD均与肾癌分期、肾包膜侵袭和淋巴结转移密切相关(P<0.05).结论 MMP-7、MVD与肾癌的浸润转移密切相关;降低MMP-7表达水平及抗肿瘤微血管形成是肾癌治疗的新目标.     

Association of VCAM-1 overexpression with oncogenesis,tumor angiogenesis and metastasis of gastric carcinoma

AIM: To investigate the relationship between the expression of vascular cell adhesion molecule-1 (VCAM-1) and oncogenesis,tumor angiogenesis and metastasis in gastric carcinoma,and to evaluate the clinical significance of serum VCAM-1levels in gastric cancer.METHODS: Specimens from 41 patients with gastric cancer, 8 patients with benign gastric ulcer, and 10 healthy subjects were detected for the expression of VCAM-1 by immunohistochemistry. Microvessel density (MVD) was measured by counting the endothelial cells immunostained with the monoclonal antibody CD34 at x200 magnification.Serum VCAM-1 concentrations were measured by an enzyme linked immunosorbent assay in the 41 gastric cancer patients before surgery, and at 7 days after surgery as well as in 25 healthy controls. The association between preoperative serum VCAM-1 levels and clinicopathological features, and their changes following surgery was evaluated. Tn addition, serum carcinoembryonic antigen (CEA) was also examined.RESULTS: Of the 41 gastric cancer tissues, 31 (75.6 %)were VCAM-1 positive. The VCAM-1 positive gastric cancers were more invasive and classified in the more advanced stage than the VCAM-1 negative ones. The VCAM-1 positive cancers were associated with more lymph node metastases than VCAM-1-negative ones (P＜0.05). The expression of VCAM-1 was detected in tissues of two of the eight patients with gastric ulcer and two of the 10 healthy controls. The expression of VCAM-1 in gastric cancer patients was significantly more frequent than that in the healthy controls and ulcer group (both P＜0.05). MVD in VCAM-1 expressing tissues was higher than that in VCAM-1 negative tissues (t=2.13,P＜0.05). Serum VCAM-1 levels in gastric cancer patients were significantly higher than those in controls (t=3.4, P＜0.05). There was a significant association between serum VCAM-1 levels and disease stage, as well as invasion depth of the tumor and the presence of distant metastases.The concentrations of serum CEA in gastric cancer were higher than normal controls. Both serum VCAM-1 and CEA levels decreased significantly after radical resection of the primary tumor (P＜0.05). Furthermore, the serum levels of VCAM-1 were positively correlated with the expression of VCAM-1 in the tumor tissue (r=-0.85, P＜0.05).CONCLUSION: The expression of VCAM-1 is closely related to oncogenesis, tumor angiogenesis and metastasis in gastric carcinoma. Serum VCAM-1 level in gastric cancer patients is significantly increased compared with normal controls, which decreases significantly after radical resection of the primary tumor. The serum concentration of VCAM-1 may be considered as an effective marker of tumor burden of gastric cancer. Moreover, overexpression of VCAM-1 in gastric cancer tissue is likely a major source of serum VCAM-1.     

Esophageal carcinoma multiplex with gastric metastasis

We describe here the radiographic findings in a patient with multiple synchronous squamous carcinomas of the esophagus with a large metastasis to the gastric cardia. Radiographic documentation of this constellation of tumor involvement has not previously been reported. The mechanisms of esophageal metastasis are reviewed.     

胃癌p53基因表达与转移及预后的研究

目的观察胃癌组织ｐ５３基因的超表达及其与预后的关系。方法用抗人Ｐ５３基因蛋白单克隆抗体Ｓ＿Ｐ免疫组织化学方法，观察１２８例胃癌组织ｐ５３表达状况，并对ｐ５３表达与胃癌淋巴结转移状态和术后５年生存率进行比较分析。结果胃癌组织１２８例的ｐ５３表达阳性率为４３８％（５６／１２８）；ｐ５３表达阳性和阴性组的胃癌局部和远处淋巴结转移率分别为６７９％（３８／５６）和５１４％（３７／７２），两者经统计学处理无显著性差异（Ｐ＞００５）。获得随访９８例，胃癌术后５年生存率的随访结果显示，ｐ５３阳性和阴性组分别为３８１％（１６／４２）和３０１％（１７／５６），两组间无统计学意义（Ｐ＞００５）。结论胃癌的发生与ｐ５３基因突变关系密切，并可用免疫组化检测，但Ｐ５３基因蛋白在胃癌组织中的超表达，似不能作为判断胃癌预后的参考指标，应进一步探讨