胃癌组织芯片p53、p16及环氧合酶-2表达的研究

目的利用高通量的组织芯片技术,对胃癌组织及癌旁组织的p53、p16和环氧合酶-2（COX-2）蛋白异常表达进行分析,探讨其相关性及临床意义。方法利用组织芯片技术结合免疫组化法检测50例胃癌组织和78例癌旁组织中p53、p16及COX-2蛋白的表达。结果p53、p16和COX-2的阳性表达率在癌旁组织中分别是19％、15％及74％;在癌组织中分别是50％、54％及94％。胃癌组织中p53、p16和COX-2蛋白表达均显著高于癌旁组织,差异具有统计学意义（P〈0．05）。p53与COX-2、p16与COX-2蛋白表达均存在相关性（P〈0．05）。当p53、COX-2表达阳性,p16阴性时;或p16、COX-2表达阳性,p53阴性时;或p53、p16和COX-2同时表达阳性时,组织芯片病理类型为癌性的概率均增加,OR值分别为11．667、30．000及18．889,p53、p16和COX-2三者存在交互作用。结论联合分析p53、p16及COX-2的表达对预测胃癌的发生和发展具有重要意义。     

食管癌和环氧合酶-2关系的研究进展

环氧化酶是花生四烯酸代谢中的一种限速酶,其中的同工酶之一的环氧合酶-2,通过多种途径与诸多肿瘤的发生、发展和预后密切相关.食管癌具有高发病率和死亡率,近年来认为环氧合酶-2通过异型生物质(xenobiotic)代谢,抑制凋亡,参与慢性炎症、免疫抑制,上调血管生成因子的表达,以及促进肿瘤的浸润和转移在其致癌中起重要作用.实验证据表明利用选择性环氧合酶-2抑制剂抑制环氧合酶-2活性可以预防各种组织中肿瘤的形成,包括食管癌.本文就环氧合酶-2对食管癌的致癌作用及选择性环氧合酶-2抑制剂的预防和/或治疗作用作一综述.     

胃癌和胃癌前病变中环氧合酶-2、p16的表达及其临床意义

背景：密切监测胃癌前病变是预防和及早发现胃癌的关键。目的：观察胃癌及其癌前病变中环氧合酶-2（COX-2）、p16的表达,探讨两者对胃癌早期诊断的意义。方法：以免疫组化染色检测20例正常胃黏膜、60例肠化生、60例上皮内瘤变和60例胃癌组织中COX-2和p16的表达,并分析两者的相关性。结果：正常胃黏膜、肠化生、上皮内瘤变和胃癌组织中的COX-2表达呈递增趋势,p16表达呈递减趋势。高级别上皮内瘤变和早期、进展期胃癌组织COX-2、p16表达阳性率与正常胃黏膜和肠化生组织相比差异有统计学意义（P〈0.05）,而前三者之间以及后两者之间无明显差异。COX-2、p16表达阳性率在小肠化生、完全型大肠化生与不完全型大肠化生之间以及早期与进展期胃癌之间无明显差异,但在高级别与低级别上皮内瘤变中差异有统计学意义（P〈0.05）。COX-2表达与p16表达呈负相关（P〈0.001）。早期胃癌组织中COX-2表达阳性同时p16表达阴性的比例显著高于高级别上皮内瘤变组织（P〈0.05）。结论：COX-2、p16或两者联合检测有助于监测和随访胃癌前病变、筛选胃癌高危人群,为胃癌的早期诊断提供了重要的检测方法。     

p53基因在食管癌组织中的高表达

本文利用免疫组化LSAB法检测了p53基因在35例食管癌组织中的表达情况。35例食管癌标本中，60％（21／35）的标本癌组织都存在有p53基因的高表达，其中18例标本同时存在有癌旁粘膜上皮p53基因在10例癌旁粘膜上皮中也存在高表达。p53的高表达主要位于核内，部分也有胞浆表达。p53基因的高表达与癌组织的分化程度有关，分化越差，阳性率越高（P＜0．0025）。p53基因的表达存在异质性，并与肿瘤细胞的浸润转移及细胞周期的不同有关。我们的结果表明，p53基因的高表达在食管癌的发生中是一个常见的基因改变，它在食管癌的发生发展中起着重要的作用。     

环氧合酶-2和胰腺癌

胰腺癌目前发病率有上升的趋势,其死亡率非常高.环氧合酶-2（COX-2）在诸多肿瘤尤其是消化道肿瘤中起着重要作用,有研究发现COX-2在胰腺癌的发生、转移、治疗和化学预防中起着重要作用.本文就此作一综述.     

应用组织芯片技术检测胃癌组织中抑癌基因、环氧合酶2和CD44的表达

新近的组织芯片技术因具有高通量、快速、多样本等特点已成为肿瘤研究的重要工具。我们采用该技术将60例患者的胃黏膜组织制成芯片，并用免疫组化对其进行死亡因子5基因（PDCD-5）、环氧合酶（COX）2、CD44的检测，以探讨胃癌组织中程序化PDCD-5、COX-2、CD44表达的意义。     

环氧合酶-2与动脉粥样硬化

动脉粥样硬化(Atherosclerosis,AS)是一种由众多炎性细胞因子参与并伴有细胞增生的血管慢性炎症反应过程.环氧合酶-2( COX-2)是COX家族的重要成员,在许多疾病中表达上调.AS病变处COX-2表达增多的现象提示COX-2在AS发生发展中具有重要作用,可能是一个抗动脉粥样硬化的新靶点.COX-2抑制剂被用来治疗AS,其安全性尚存在争议.     

环氧合酶-2与胃癌

环氧合酶(COX)是合成前列腺素(PG)过程中一个重要的限速酶,有COX-1和COX-2两种异构体.近年来的研究表明,COX-2与多种肿瘤的发生发展密切相关.此文就COX-2与胃癌的关系以及COX-2抑制剂治疗胃癌的研究进展作一综述.     

环氧合酶-2与肺癌

本文就环氧合酶 2 (COX 2 )在肿瘤发生、发展、预后中的研究现状以及COX 2和COX 2抑制剂在肺癌中的作用作一综述。COX 2抑制剂可能成为治疗肺癌的新途径。     

胃癌组织环氧合酶-2表达与血管内皮生长因子的关系

目的 观察胃癌环氧合酶-2和血管内皮生长因子的表达及相互关系。方法 应用免疫组化法检测胃癌组织COX-2和VEGF的表达状况。结果 32例胃癌中发现COX-2表达阳性22例(68.7％),其中伴淋巴结转移者COX-2表达阳性率80.9％(17/21),高于不伴淋巴结转移者的45.4％(5/11)(P<0.05)。而不同胃癌分期与组织类型之间COX-2表达无显著性差异(P>0.05)。32例胃癌中VEGF表达阳性20例(62.5％),其中COX-2阳性胃癌VEGF表达阳性率77.3％(17/22),而COX-2阴性胃癌VEGF阳性率30％(3/10),两组比较具有显著性差异(P<0.05)。结论 胃癌组织存在COX-2过度表达,且与VEGF表达相关。     

Expression of p53, p16 and cyclooxygenase-2 in esophageal cancer with tissue microarray

OBJECTIVE: The aim of this study was to obtain a comprehensive survey on the expression of p53, p16 and cyclooxygenase‐2 (COX‐2) in esophageal cancer progression and their clinical significance. METHODS: A tissue microarray containing 86 specimens from esophageal cancer and 40 specimens from adjacent non‐cancer tissue was constructed to survey the expression of p53, p16 and COX‐2 by immunohistochemistry. The influence of each biomarker on the histotype of esophageal lesion was assessed by logistic regression analysis. RESULTS: The expression of p53 and COX‐2 was significantly higher in tumorous tissue than in non‐tumorous tissue. As to p16, no significant difference was detected between tumorous and non‐tumorous tissue. A significant correlation was observed among p53, COX‐2 and p16 expression. Logistic regression analysis revealed that the risk factors of a tumorous histotype were the positive expression of p53 (odds ratio [OR] = 18.214) or COX‐2 (OR = 42.703), and no reciprocal relationship to neoplastic progression was recognized with p53, p16 and COX‐2. CONCLUSIONS: p53 and COX‐2 were independent predictors in esophageal carcinogenesis. Esophageal tissue with a positive expression of p53 or COX‐2 was more likely to develop esophageal cancer.     

Expression of p53, p16 and COX-2 in pancreatic cancer with tissue microarray

BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxyganase-2 (COX-2). METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent noncancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections. RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorons ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2. CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.     

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．     

Analysis of cyclooxygenase-2 expression in human breast cancer: high throughput tissue microarray analysis

Purpose The objective of this study was to evaluate breast carcinomas for the expression of cyclooxygenase-2 (Cox-2) using a tissue microarray (TMA) and to determine its clinical and prognostic relevance.Methods We analyzed Cox-2 expression in 600 samples from 200 breast carcinomas immunohistochemically performing TMA technology and semiquantitative analysis. Results were correlated with various clinicopathological variables and follow-up data. Expression of estrogen receptor, progesterone receptor, Ki-67, and Her-2/neu-oncogene was analyzed and correlated with Cox-2 status.Results We observed a moderate or strong cytoplasmic staining for Cox-2 in 78 (40.6%) of breast carcinomas. Increased Cox-2 expression corresponded to higher pT stage (P=0.038), amplification of Her-2/neu (P=0.032), lymphovascular invasion (P=0.006), a high MIB-1 labeling index (LI) (P<0.001), and histological grading (P=0.013). We also observed an inverse relationship between strong Cox-2 expression and estrogen and progesterone receptor content of tumors (P=0.037 and P=0.010). However, we could not demonstrate a significant association between Cox-2 staining and overall survival or disease free survival time.Conclusions These results suggest that Cox-2 expression is significantly associated with less differentiated and more aggressive breast carcinomas and might therefore be a useful prognostic indicator as well as a target for therapy.     

食管癌环氧化酶-2的高表达与淋巴转移的关系

目的　探讨环氧化酶 -2 (COX -2 )在食管癌中的表达情况及其与淋巴结转移的关系。方法　应用免疫组织化学方法(SP法 ) ,检测 1999～ 2 0 0 1年手术切除的 76例食管癌病人中COX -2的表达。其中有食管旁淋巴结转移者 18例 ,胃左动脉旁淋巴结转移者 11例。结果　COX -2在食管癌中的表达率为 81 6 %,主要为癌组织的表达 ,而在癌旁组织几乎不表达 ;食管癌旁和胃左动脉旁淋巴结转移组COX -2的表达水平均高于未转移组 (P <0 0 0 1)。结论　食管癌中COX -2的高度表达与食管癌的发生、发展及淋巴结转移有关 ,提示COX -2可能是防治食管癌的一个靶位。     

Expression of cyclooxygenase-2 is associated with p53 accumulation in premalignant and malignant gallbladder lesions

AIM: To examine the relationship between cyclooxygenase-2 (COX-2) overexpression and p53 accumulation in gallbladder carcinoma and its precursor lesions. METHODS: Sixty-eight gallbladder tissue samples comprising 14 cases of normal gallblader epithelium, 27 cases of dysplasia (11 low-grade dyplasia and 16 high-grade dysplasia) and 27 adenocarcinomas were evaluated by immunohistochemistry for COX-2 expression and p53 accumulation. The relationship among COX-2 expression, p53 accumulation and clinicopathological characteristics was analysed. RESULTS: COX-2 was expressed in 14.3% of normal gallbladder epithelium, 70.3% of dysplastic epite hlium, and 59.2% of adenocarcinomas. When divided into low- and high-grade dysplasia, COX-2 was positive in 5 (45.4%) cases of low-grade and 14 (87.5%) of high-grade dysplasia (P = 0.019). Accumulation of p53 was detected in 5 (31.2%) cases of high-grade dysplasia and in 13 (48.1%) of carcinomas. No p53 accumulation was found in normal epithelium or low-grade dysplasia. COX-2 overexpression was observed in 17 of 18 (94.4%) cases with p53-accumulation in comparison with 20 (40.0%) out of 50 cases without p53 accumulation (P < 0.001). CONCLUSION: The significant differences in COX-2 expression among normal epithelium, low-grade dysplasia and high-grade dysplasia suggest that overexpression of COX-2 enzyme is an early event in gallbladder carcinogenensis. Furthermore, since accumulation of p53 correlates with COX-2 expression, COX-2 overexpression observed in gallbladder high-grade dysplasia and carcinoma might be partly due to the dysfunction of p53.     

食管癌组织环氧化酶-2的表达与血管生成的关系

目的:探讨环氧化酶-2(COX-2)在食管癌组织的表达及其与肿瘤血管生成的关系．方法:免疫组化法检测食管鳞癌手术切除标本90例和癌旁正常黏膜34例中COX-2表达,采用抗CD34抗体标记微血管内皮细胞,计算微血管密度(MVD)．分析COX-2表达与MVD及其与食管癌主要临床病理特征的相关性．结果:食管癌组织COX-2阳性表达率为84．4％显著高于癌旁正常黏膜的20．6％(x2=45．47,P =0．00)．COX-2表达与肿瘤细胞分化程度、临床TNM分期和淋巴结转移密切相关,TNM分期中Ⅲ Ⅳ期的食管鳞癌组织中COX-2表达率为92．9％,显著高于Ⅰ Ⅱ期的70．6％(x2= 7．99,P=0．005)．高、中分化的食管鳞癌组织中COX-2表达率为92．9％,显著高于低分化的 70．6％(x2=7．99,P=0．005)．伴有淋巴结转移的食管鳞癌组织中COX-2表达率为94．3％,显著高于无淋巴结转移的70．3％(x2=9．61,P= 0．002)．食管癌组织MVD值为29．68±3．81, 显著高于癌旁正常黏膜的15．12±2．80(t= 20．28,P=0．00)．MVD与肿瘤的TNM分期和淋巴结转移密切相关,TNM分期中Ⅲ Ⅳ期的食管鳞癌组织中MVD值为31．46±3．52,显著高于Ⅰ Ⅱ期的26．74±2．06(t=-7．09,P=0．00)．伴有淋巴结转移的食管鳞癌组织中MVD为 31．72±3．43,显著高于无淋巴结转移的26．76 ±2．01(f=-7．90,P=0．00)．Spearman等级相关分析表明,MVD与COX-2表达呈显著正相关(r =0．607．P=0．00)．结论:COX-2异常表达及其诱导的血管生成在食管癌的侵袭和淋巴结转移中起重要作用．     

环氧合酶—2在胰腺癌中的表达及其临床意义

目的 探讨胰腺癌中COX-2的表达及其临床意义、方法 应用免疫组化SP法检测45例胰腺癌、11例慢性胰腺炎、7例胰腺良性肿瘤和10例正常胰腺组织中COX-2的表达。结果 正常胰腺和慢性胰腺炎组织的导管上皮和腺泡细胞未见COX-2的表达,7例良性胰腺肿瘤有2例COX-2呈阳性表达,45例胰腺癌中,有34例COX-2呈阳性表达,阳性率为75.6％。COX-2在胰腺癌中的表达显著高于正常胰腺、慢性胰腺炎和胰腺良性肿瘤(X_2分别为19.79、21.16和6.28,P<0.0001、P0.05)。结论 COX-2的过度表达在胰腺癌的发生中可能具有重要作用,COX-2抑制剂对胰腺癌的预防和治疗可能有效。     

Mutations of p53 gene exons 4-8 in human esophageal cancer

AIM: To characterize the tumor suppressor gene p53 mutations in exon 4, esophageal cancer and adjacent non-cancerous tissues. METHODS: We performed p53 (exons 4-8) gene mutation analysis on 24 surgically resected human esophageal cancer specimens by PCR, single-strand conformation polymorphism, and DNA sequencing. RESULTS: p53 gene mutations were detected in 9 of 22 (40.9%) esophageal cancer specimens and 10 of 17 (58.8%) adjacent non-cancerous tissues. Eight of sixteen (50.0%) point mutations detected were G-A transitions and 9 of 18 (50.0%) p53 gene mutations occurred in exon 4 in esophageal cancer specimens. Only 1 of 11 mutations detected was G-A transition and 4 of 11 (36.4%) p53 gene mutations occurred in exon 4 in adjacent non-cancerous tissues. CONCLUSION: Mutation of p53 gene in exon 4 may play an important role in development of esophageal cancer. The observation of p53 gene mutation in adjacent non-cancerous tissues suggests that p53 gene mutation may be an early event in esophageal carcinogenesis. Some clinical factors, including age, sex, pre-operation therapy and location of tumors, do not influence p53 gene mutation rates.