生存素基因在胃癌组织中的表达及其与胃癌预后关系

目的探讨生存素(survivin)基因在胃癌组织中的表达及其与胃癌预后关系。方法病例来源于1995年7月至1996年6月中山医院住院手术患者，采用免疫组化Envision二步法检测手术切除的胃癌病灶组织中生存素基因表达。根据手术病理诊断与临床表现确定肿瘤TNM分期。所有病例随访至少5年或直到死亡。比较不同病理类型、不同TNM分期生存素表达差异。按生存素基因是否表达比较两组患者生存曲线的差异。结果共有96例患者进入研究和随访观察，其中男59例，女37例；年龄29～84岁，平均56岁，68例表达生存素基因产物，阳性率70．8％。病理类型中腺癌78例，非腺癌18例，不同病理类型生存素基因表达相似(腺癌69．7％、非腺癌60．0％，P=0．369)。对腺癌病例分析显示：低分化组生存素基因表达高于中高分化组(82．1％比62．5％，P=0．053)；肿瘤累及固有肌层组和全层组生存素基因表达高于肿瘤局限于黏膜或黏膜下层组(81．3％，75．9％比33．3％，P=0．020)。生存素表达与淋巴结转移与否无关(68．1％比70．8％，P=0．771)。生存素阳性组5年生存率(42．93％)低于生存素阴性组(52．93％)，但差异无统计学意义。结论生存素基因在胃癌中高表达。生存素基因表达与胃腺癌分化程度以及肿瘤累及深度有关，需进行更多研究评价其在预后中的作用。     

Galectin-1在胃癌组织中的表达及在胃癌血管生成中的作用

目的研究半乳糖凝集素1（Gal-1）在胃癌组织中的表达,并分析其与肿瘤血管生成的关系。方法采用实时荧光定量RT-PCR技术从mRNA水平检测胃癌组织及远癌切端胃组织中Gal-1的表达情况,并用免疫组织化学SABC法检测各标本中Gal-1蛋白、血管内皮生长因子（VEGF）表达及其微血管密度（MVD）。分析Gal-1、VEGF与临床病理参数及MVD之间的关系。结果胃癌组织Gal-1 mRNA及蛋白表达、VEGF表达、MVD均分别高于远癌切端胃组织（P均〈0.05）。胃癌组织Gal-1 mRNA及蛋白表达、VEGF表达和MVD与浸润深度、TNM分期及淋巴结转移相关,胃癌组织Gal-1表达与VEGF、MVD呈正相关（P〈0.05）。结论 Gal-1通过促进肿瘤微血管生成参与胃癌的生长和侵袭,可作为诊断及判断胃癌进展程度及预后的指标。     

COX-2 expression in gastric cancer and its relationship with angiogenesis using tissue microarray

AIM： To explore the expression and clinicopathological significance of cyclooxygenase-2 （COX-2） and microvessel density （MVD） in gastric carcinogenesis, and to investigate their roles in the invasion and the relationship between biological behaviors and prognosis of gastric cancer.
METHODS： Using Envision immunohistochemistry, COX-2 and CD34 expressions in gastric cancer tissue array were examined. MVD was counted and the relationship between the biological behaviors and prognosis was analyzed.
RESULTS： The expression of COX-2 in gastric cancer tissue was significantly higher than that in normal mucosa （χ^2 = 12.191, P 〈 0.05）. The over-expression of COX-2 in gastric cancer was obviously related to metastasis and depth of invasion （χ^2 = 6.315, P 〈 0.05）, but not related to the histological type and Borrmann type （χ^2 = 5.391 and χ^2= 2.228, respectively）. Moreover, MVD in gastric cancer tissues was significantly higher than that in the normal mucosa （65.49 ± 20.64 vs 36.21 ± 18.47, t/F = 7.53, P 〈 0. 05）. MVD was related to the histologic type and metastasis （t/F= 3.68 and t/F = 4.214, respectively, P 〈 0. 05）, but not related to the depth of invasion and Borrmann type （t/F = 0.583 and t/F = 0.459, respectively）. MVD in COX-2-positive tissues was markedly higher compared to COX-2-negative tissues, indicating a positive correlation between COX-2 expression and MVD （t = 13.12, P 〈 0. 05）.
CONCLUSION： Tissue microarray （TMA） is a powerful tool for rapid identification of the molecular alterations in gastric cancer. COX-2 expression, via inducingangiogenesis, may play an important role in gastric carcinogenesis. It could be served as a determinant factor for clinical prognosis and curative effect.     

Expression of survivin and caspase-3 in gastric cancer

Gastric cancer is one of the most common malignant tumors of the gastrointestinal tract. However, the molecular pathways involved in the regulation of gastric carcinogenesis are not completely elucidated. In the last decade, basic cancer research has been focused on the deregulation of apoptosis as a central event in the process of carcinogenesis. Caspase-3 and survivin are regulators of apoptosis and have been implicated in the development of gastric cancer. The aim of the present study was to compare the expression of mRNA and protein for survivin and caspase-3 in the gastric cancer and in the cancer margin with that in normal human gastric mucosa. Fifteen patients with advanced gastric cancer (all H. pylori-positive) and 15 matched control subjects with normal gastric mucosa were included in this study. The biospy specimens for histology and for molecular analyses were taken from gastric tumor, tumor surrounding gastric mucosa and in normal patients from the mucosa of antrum and corpus. Survivin mRNA expression was very weak, but detectable, in the normal gastric mucosa. However, at the protein level, no expression for survivin was detected in the normal gastric mucosa. In the biopsy specimens from tumor and surrounding gastric mucosa, a significant increase in survivin mRNA and protein expression was observed. The expression of survivin was higher in the tumor than in the tumor margin. The mRNA and protein expression of caspase-3 was detected in the gastric mucosa of normal subjects. In gastric cancer only the expression of procaspase-3 was observed, while the expression of active caspase-3 was completely undetectable. In the gastric mucosa surrounding gastric cancer, no gene and protein expression for caspase-3 was detected. We conclude that the changes in the level of caspase-3 and survivin play an important role in the transformation from normal gastric mucosa to gastric career.     

DLL4在胰腺癌组织中的表达及其与肿瘤血管生成的关系

目的 检测delta-like ligand 4(DLL4)在胰腺癌中的表达,分析其与肿瘤血管生成及临床病理特征的关系.方法 采用免疫组化SP法检测60例胰腺癌组织及20例癌旁正常胰腺组织中DLL4的表达;观察微血管内皮细胞CD34表达,计算微血管密度(MVD);分析DLL4表达、MVD与胰腺癌临床病理特征之间的关系以及两者的相关性.结果 DLL4在胰腺癌组织中的表达明显高于正常胰腺组织(68.3％比20.0％,P＜0.01);胰腺癌组织DLL4的高表达与肿瘤分化程度、TNM分型、肿瘤转移及浸润等呈正相关(P值均＜0.05),而与肿瘤部位、大小、组织病理分型无关.胰腺癌组织MVD明显高于正常胰腺组织(34.9±13.2比18.9±2.2,P＜0.01);胰腺癌的MVD与肿瘤分化程度、TNM分期、肿瘤转移及浸润有关(P值均＜0.05),而与肿瘤部位、大小、组织病理分型等无明显相关性.DLL4表达阳性的胰腺癌组织MVD明显高于DLL4表达阴性者(38.8±10.7比29.0±15.2,P＜0.05),且DLL4表达与MVD呈显著正相关(r=0.669,P＜0.05).结论 DLL4表达可促进肿瘤血管生成,且与胰腺癌的转移、浸润相关.     

Expression of monocyte chemotactic protein-1/CCL2 in gastric cancer and its relationship with tumor hypoxia

AIM:To investigate the expression and prognostic value of CCL2 in gastric cancer,as well as its relationshipwith tumor hypoxia.METHODS:Tumor tissues from 68 gastric cancer patients(GC)were analyzed,and the expression of CCL2and hypoxia-inducible factor 1 alpha(HIF-1α)in tumortissues was detected by immunohistochemistry.Statistical evaluations that were used included univariate logrank tests of Kaplan-Meier curves and multivariate Coxregression model analysis.RESULTS:CCL2 was highly expressed in 66.2%(45/68)of gastric cancer specimens.The distribution of CCL2expression in tumor tissue was consistent with thatof HIF-1α.Patients with high CCL2 expression in GChad a lower overall survival rate[50.6 mo(95%CI:44.44-56.93)vs 64.6 mo(95%CI:60.27-68.94),P=0.013].CONCLUSION:CCL2 expression correlates closely with HIF-1αexpression in gastric cancer.CCL2 may be an independent prognostic marker for GC.     

大肠癌CD24的表达及其与肿瘤细胞增殖和血管形成的关系

目的:探讨CD24在大肠癌中的表达及其与细胞增殖、血管生成的关系.方法:运用流式细胞术直接免疫荧光法检测66例大肠癌肿瘤组织及相应正常大肠黏膜CD24的表达量.CD24蛋白表达量以阳性率(PPC)和平均荧光强度MFI值表示.运用免疫组织化学法检测肿瘤组织CD34,PCNA的表达情况,根据CD34的染色情况计算出大肠癌组织的微血管密度(microvessel density),根据PCNA染色情况计算出肿瘤细PCNA标记指数.结果:大肠癌肿瘤组织CD24阳性率90.40%(75.10%-96.35%)明显高于相应的癌旁组织36.15%(32.00%-53.28%)(χ2=6.877,P＜0.001).大肠癌肿瘤组织CD24蛋白MFI值18.10(11.45-25.43),明显高于正常黏膜组织8.41(5.59-10.33)(χ2=6.934,P＜0.001).浸润型、高Dukes分期、高pTNM分期及有淋巴结转移的癌组织中CD24蛋白的平均荧光强度显著高于对应组(P＜0.05).浸润型、低分化、高Dukes分期、高pTNM分期及有淋巴结转移的癌组织中CD24蛋白阳性百分率显著高于对应组(P＜0.05).在CD24阳性表达病例中,PCNA的表达随着CD24表达强度的升高而升高(P＜0.05).大肠腺癌肿瘤细胞CD24阳性表达率与MVD呈正相关(r=0.243,P=0.050).而CD24蛋白平均荧光强度与MVD未见明显相关(r=0.115,P=0.358).结论:CD24在大肠腺癌中表达水平明显上调,并与肿瘤细胞增殖、血管生成密切相关.     

胃癌组织碱性成纤维细胞生长因子表达及对血管新生和肿瘤进展的影响

目的　探讨碱性成纤维细胞生长因子 (bFGF)在胃癌组织中表达及其对血管新生和肿瘤生物学行为的影响。方法　应用免疫组化SP法检测 74例胃癌 ,17例癌旁组织bFGF表达及间质微血管密度 (MVD)。结果　胃癌组织中肿瘤细胞、间质新生血管高度表达bFGF。癌组织bFGF表达(77.0 3% )明显高于癌旁组织 (2 9.4 1% ,P <0 .0 1)。癌旁胃黏膜及伴有肠上皮化生的胃黏膜表达bFGF较弱。bFGF高表达组的平均MVD值 (79.3± 11.2 )明显高于bFGF低表达组 (71.2± 11.9,P <0 .0 5 )。此外bFGF表达程度与胃癌淋巴结转移和癌浸润深度密切相关。结论　bFGF可促进肿瘤间质微血管生成 ,加速肿瘤浸润和转移。     

利用组织芯片技术研究COX-2在胃癌中的表达及其与血管生成的关系

目的:研究COX-2在胃癌中的表达及其与血管生成的关系,探讨其在胃癌转移中的作用及与胃癌病理生物学行为的关系．方法:采EnVision方法检测胃癌组织芯片中 COX-2的表达,用CD34进行微血管内皮细胞染色,计算微血管密度(MVD),分析其相关性．结果:COX-2在胃癌中的表达明显高于正常胃黏膜(P=0．001)．COX-2的高表达与胃癌的转移(P=0．019)和胃壁浸润深度(0．031)呈正相关,与胃癌的组织病理分型无关(P=0．495), 与Borrmann分型无关(P=0．109)组织MVD (65．49±20．64)明显高于正常胃黏膜组织 (36．21±18．47,P=0．001)．MVD值与胃癌的组织病理分型(P=0．003)和转移有关(P=0．043), 与胃癌胃壁浸润深度(P=0．627)和Borrmann 分型(P=0．634)无明显相关性．COX-2表达阳性组的MVD指数明显高于COX-2表达阴性组 (68．59±19．8 vs 25．82±7．76．P<0．05),COX-2 表达与MVD呈正相关(P=0．001)．结论:组织芯片技术对于快速检测胃癌及其他肿瘤的分子病理学改变是一个强有力的工具．COX-2表达可能通过促进血管形成对胃癌的发生、发展起重要作用,其可作为判断预后和指导治疗的有效指标．     

环氧化酶-2在胃癌和胃炎中的表达及其与幽门螺杆菌感染的关系

目的探讨环氧化酶-2(COX-2)在胃癌和胃炎中的表达及其与幽门螺杆菌(Helicobater pylori,HP)感染的关系,为胃癌的预防和治疗提供有价值的实验和理论依据。方法2004年11月至2005年4月中国医科大学附属第一医院门诊胃镜活检标本共128例,采用免疫组化技术检测COX-2在胃癌以及各型胃炎中的表达情况。结果胃癌和萎缩性胃炎伴不典型增生组织中COX-2的表达率明显高于浅表性胃炎(P<0.05),COX-2在萎缩性胃炎伴不典型增生HP感染阳性患者中的表达率明显高于HP感染阴性患者(P<0.05),高、中分化胃癌COX-2表达率高于低分化胃癌(P<0.05)。结论COX-2在胃癌组织中存在过表达,HP感染可使萎缩性胃炎伴不典型增生组织中COX-2表达增强,COX-2表达与胃癌分化程度有关。     

胃癌发生过程中凋亡基因Survivin与Fas表达及其与幽门螺杆菌感染的关系

目的探讨凋亡基因Survivin、Fas在胃癌发生过程中的表达、临床意义及和幽门螺杆菌（Hp）感染的关系。方法采用分子原位杂交分别检测12例正常胃黏膜、22例浅表性胃炎、25例肠上皮化生、37例异型增生及52例胃癌组织中的Survivin-mRNA和Fas-mRNA表达，并检测患者Hp感染状况。结果Survivin-mRNA在肠上皮化生、异型增生组和胃癌组织中的阳性率分别为28．0％、43．2％和69．2％。胃癌组明显高于肠化和异型增生组（P〈0．01；P〈0．05）。胃癌组Fas-mRNA阳性率为36．5％，显著低于对照组和异型增生组（P均〈0．01）。Survivin-mRNA在高分化、中分化和低分化及未分化型胃癌组织中阳性率呈现递增趋势，而且其表达和淋巴结转移、远处转移密切相关。Fas-mRNA阳性率在高、中和低分化及未分化型胃癌患者中呈现递减趋势，且其表达和淋巴结转移密切相关。异型增生患者Survivin-mRNA表达与Hp感染之间呈明显正相关（P〈0．01）。相关回归分析显示胃癌患者各病理分期中Survivin-mRNA与Fas-mRNA表达呈负相关。结论在胃黏膜癌变过程中，Survivin的表达和作用逐渐上调，而Fas的表达和作用逐渐下调，而且在癌前病变组织中Survivin表达和Hp感染有密切关系；在胃癌组织中Survivin和Fas的表达呈负相关。     

胃癌组织MMP-10和VEGF表达与血管生成的关系

目的:研究胃癌组织中基质金属蛋白酶- 10(MMP-10)、血管内皮生长因子(VEGF)和微血管密度(MVD)表达变化及其与肿瘤临床病理特征之间的关系.方法:以CD31作为MVD指标,应用免疫组化法检测60例胃癌组织和60例距病灶5 cm以上的正常组织中的MMP-10、VEGF和CD31的表达并对结果进行分析.结果:60例胃癌组织中的MMP-10、VEGF的表达阳性率分别为81.7%、76.7%,明显高于正常组织的表达阳性率11.7%、8.3%,两者差异有统计学意义(P<0.05).MMP-10、VEGF的表达与MVD、与肿瘤的分化程度、TNM分型、淋巴结的转移、浸润程度有关.结论:MMP-10、VEGF胃癌组织中高表达与胃癌侵袭转移、血管生成密切相关,可作为判断胃癌侵袭转移及预后的重要指标.     

Expression of PTEN and its correlation with angiogenesis in gastric carcinoma]

BACKGROUND/AIMS: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a recently clarified tumor suppressor gene located in 10q23.3. Alterations of this gene are associated with tumor progression and unfavorable outcome in various human cancers. Recently, PTEN has a possible role in angiogenesis by modulating angiogenic factor including vascular endothelial growth factor (VEGF). The aim of this study was to investigate the roles of PTEN and VEGF status for angiogenesis in human gastric cancer. METHODS: We conducted an immunohistochemical investigation of PTEN and VEGF expression in 90 cases of paraffin section obtained from gastric cancer patients undergone surgical treatment. RESULTS: Negative expression of PTEN and positive expression of VEGF in gastric cancer tissues, were demonstrated in 40.0% and 77.8% of cases, respectively. However, no significant correlation was found between PTEN, VEGF expression and various clinicopathological parameters. PTEN expression did not correlate significantly with VEGF expression (p=0.301). High microvessel density (MVD) was significantly associated with lymph node metastasis and poor survival (p=0.014, 0.011, respectively). The mean MVD value of PTEN negative tumors was 90.4+/-43.0 and significantly higher than that of PTEN positive tumors (p=0.028). The mean MVD value of VEGF positive tumors was 86.4+/-6.7 and significantly higher than that of VEGF negative tumors (p=0.002). The mean MVD value of PTEN negative and VEGF positive tumors was 98.0+/-42.2, and significantly higher than those of the others. CONCLUSIONS: These results suggest that loss of PTEN expression may play a critical role in tumor progression and metastasis by stimulating tumor angiogenesis in human gastric cancer.     

Survivin、COX-2及VEGF在大肠癌中的表达及与肿瘤微血管密度的关系

目的:研究Survivin, COX-2, VEGF和肿瘤微血管密度(MVD)在大肠癌组织中的表达, 探讨其与大肠癌肿瘤血管生成的关系.方法:2007-09/2008-05哈尔滨医科大学附属第二临床医学院内镜下取材的大肠癌、肠息肉及肠炎标本. 所有标本均经病理检查证实诊断. 试验对象共分3组, 分别为大肠癌组织26例, 大肠息肉组织10例, 大肠黏膜慢性炎症组织7例. 采用免疫组织化学方法检测Survivin,COX-2, VEGF和CD34在大肠组织中的表达.结果:Survivin, COX-2与VEGF蛋白在大肠癌组织中阳性表达率分别为76.9%, 80.8%和69.28%, 明显高于大肠息肉组与肠炎组的表达( P<0.01或0.05). 大肠癌组织中MVD(CD34)明显高于大肠息肉组与肠炎组(23.69±9.96 vs13.10±7.05, 10.43±4.24, 均P<0.01). Survivin,COX-2和VEGF蛋白在大肠癌组中的表达与MVD相关(均P<0.05), Survivin和促血管形成因子COX-2, VEGF在大肠癌组织中的表达密切相关(χ2 = 11.18, 4.72, 均P<0.005).结论:Survivin可能通过COX-2, VEGF促进大肠癌肿瘤血管的形成.     

survivin在宫颈癌组织中的表达及临床意义

目的探讨survivin在宫颈癌组织中的表达及临床意义。方法采用免疫组化法检测survivin在60例宫颈癌及10例慢性宫颈炎组织中的表达,分析其与肿瘤临床病理特征的关系。结果survivin在宫颈癌及慢性宫颈炎组织中的阳性表达率分别为68．33％、10％,P〈0．001;survivin在宫颈癌组织中的表达与患者年龄、肿瘤大小、病理分级、临床分期无相关性（P〉0．05）,与病理类型及淋巴结转移情况有显著相关性（P〈0．05、〈0．01）;SUF-vivin阳性表达者中位生存期、3a生存率均小于阴性表达者（P〈0．05）。结论survivin阳性表达可成为评判宫颈癌诊疗及预后的参考指标。     

食管癌癌组织中survivin基因的表达及其意义

目的探讨食管癌癌组织中survivin基因表达的临床意义。方法采用RT-PCR法检测52例食管癌手术切除标本中survivinmRNA的表达,免疫组化法检测152例食管癌手术切除标本中survivin和p33^INC1蛋白表达以及187例食管活检标本中survivin蛋白的表达。结果①食管癌手术切除标本中,survivin mRNA及蛋白的表达明显高于食管正常黏膜（P〈0．05）;survivin mRNA及蛋白在胞质中表达与肿瘤病理特征无关（P〉0．05）,但survivin蛋白在胞质和胞核同时表达时,与肿瘤浸润深度及淋巴结转移有关（P〈0．05）。②食管活检标本中,survivin蛋白在食管由正常向癌转变过程中,表达逐渐增高（P〈0．05）。③食管癌手术切除标本中,survivin与p33^INC1.蛋白表达呈负相关（P〈0．05）。结论①survivin基因的再次激活表达与食管癌发生、发展有关,survivin基因的转录异常启动是survivin再表达的关键机制,survivin蛋白核定位预示食管癌具有较强的侵袭和转移潜能。②survivin功能的激活和p33^INC1功能的下调共同对抗细胞凋亡,参与食管癌的发生、发展。     

Overexpression of cyclooxygenase-2 and tumor angiogenesis in human gastric cancer

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) protein is overexpressed in various cancers, including esophageal, gastric, colon, and pancreatic. To better comprehend the role of COX-2 in gastric cancer, especially with regard to angiogenesis, we investigated COX-2 and vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in 108 patients with gastric cancer. METHODOLOGY: We used immunohistochemical analysis of formalin-fixed tissues of gastric cancer. RESULTS: Expression of COX-2 showed diffuse staining in the cytoplasm of tumor cells, however, no staining in normal epithelial cells. Of the 108 tumors examined, 71 (65%) were positive for COX-2 expression, the VEGF-positive cases numbered 43 of 108 cases (39.8%). The intensity of COX-2 expression did not correlate with any clinicopathological characteristics. The positive rate of VEGF expression in COX-2-positive cases was significantly higher than in COX-2-negative ones (47.9% vs. 24.3%, P<0.05). MVD in COX-2-positive cases was significantly higher than in COX-2-negative ones (22.0+/-7.8 vs. 18.5+/-7.5/1 mm2; P<0.05). CONCLUSIONS: Our study provides evidence that COX-2 is closely related with angiogenesis.