Slug和E-cadherin在结直肠癌组织中的表达及临床意义

目的探讨Slug和E-cadherin在结直肠癌组织中的表达及预后意义。方法应用免疫组化SP法检测65例结直肠癌组织,25例癌旁正常结直肠组织中Slug和E-cadherin的表达,分析两者表达水平与临床病理特征及患者预后的关系。结果 Slug在结直肠癌组织中异常表达率为47.1%,而在正常结直肠组织中表达率为12%,差异有统计学意义(P<0.01);E-cadherin在结直肠癌组织中异常表达率为55.4%,而在正常结直肠组织中表达率为8%,差异有统计学意义(P<0.01);两者阳性表达率与肿瘤浸润深度、分化程度、淋巴结转移、Dukes分期相关性均有统计学意义(P<0.05)。Slug、E-cadherin、淋巴结转移、Dukes分期可成为影响结直肠癌预后的独立因素(P<0.05)。结论 Slug和E-cadherin的表达异常可能与结直肠癌的发生发展、转移相关并可作为评价结直肠癌生物学行为和预后的重要指标。     

结直肠癌组织中COX-2、MLVD的表达变化及意义

目的观察结直肠癌组织中环氧化酶2(COX-2)、微淋巴管密度(MLVD)的表达变化,探讨其与肿瘤淋巴转移的关系。方法收集结直肠癌标本50例作为实验组,并取相应的癌旁组织作为对照组,采用免疫组化方法检测两组组织中COX-2及MLVD的表达。结果结直肠癌组织中,COX-2表达、MLVD均明显高于癌旁组织(P<0.01);结直肠癌组织中COX-2表达与MLVD呈正相关(r=0.601,P<0.01)。结论结直肠癌组织中COX-2表达、MLVD明显上调,其在结直肠癌淋巴转移中发挥重要作用。     

结直肠癌组织中ET-1、EGFR的表达及其与临床病理特征的关系

目的探讨结直肠癌组织中内皮素-1(ET-1)、表皮生长因子受体(EGFR)的表达及其与临床病理特征的关系。方法选择132例结直肠癌患者,取其癌组织及癌旁正常组织,采用免疫组化法检测ET-1、EGFR的表达,并分析其与临床病理特征的关系。结果 ET-1、EGFR在结直肠癌组织中的阳性表达率分别为72.0%、67.4%,均高于癌旁正常组织(20.5%、6.8%)(P均<0.01);ET-1的阳性表达与肿瘤分化程度、Dukes分期和淋巴结转移有关(P均<0.05);EGFR的阳性表达与Dukes分期、淋巴结转移有关(P均<0.05);ET-1和EGFR在结直肠癌组织中的表达呈正相关(rs=0.793,P<0.01)。结论 ET-1、EGFR的表达与结直肠癌浸润和转移密切相关,可为结直肠癌患者的预后判断提供客观依据。     

CDX2和p120ctn在结直肠癌组织中的临床意义

目的探讨尾端相关同源异形盒基因(CDX2)与p120-连环蛋白(p120ctn)在结直肠癌组织中的表达与其浸润、转移及预后的关系。方法采用免疫组织化学方法检测60例结直肠癌组织及20例正常大肠组织中CDX2与p120ctn的表达。结果大肠癌组织中CDX2与p120ctn表达低于正常大肠组织(P<0.05)。60例结直肠癌CDX2与p120ctn阳性表达率均与肿瘤的组织学分级、浸润程度、临床TNM分期及淋巴结转移有关(P<0.05)。二者在结直肠癌组织中阳性表达呈正相关(r=0.735,P<0.01))。结论 CDX2与p120ctn表达与结直肠癌的发生、浸润、转移有关,可联合判断预后。     

Bves/popdc1、popdc3在结直肠癌中的表达和意义

背景:结直肠癌为常见消化道恶性肿瘤,较易发生肝、肺等远处转移,预测其远处转移风险对于指导综合治疗和判断预后具有重要意义。细胞黏附分子与肿瘤侵袭、转移关系密切。目的:检测结直肠癌组织中的细胞黏附分子Bves/popdc1、popdc3表达,探讨两者在结直肠癌侵袭、转移中的可能作用。方法:选择15例正常结直肠组织和70例结直肠癌手术标本,以免疫组化方法检测Bves/popdc1、popdc3表达,分析结直肠癌组织中的Bves/popdc1、popdc3表达与肿瘤临床病理特征的关系以及两种蛋白表达之间的相关性。结果:Bves/popdc1、popdc3在结直肠癌组织中以低表达为主,高表达率显著低于正常结直肠组织(Bves/popdc1:25.7%对86.7%,P=0.000;popdc3:20.0%对73.3%,P=0.000)。结直肠癌组织中的Bves/popdc1、popdc3低表达与肿瘤分化程度呈负相关(P<0.05),与肿瘤浸润、淋巴结转移、远处转移和TNM分期呈正相关(P<0.05)。Bves/popdc1与popdc3在结直肠癌组织中的表达呈显著正相关(P<0.01)。结论:Bves/popdc1、popdc3在结直肠癌组织中表达下调,并与肿瘤临床分期和转移相关,提示两者在结直肠癌的侵袭、转移中起一定作用。     

缺氧诱导因子-1α和血管内皮生长因子在结直肠癌组织中的表达及意义

目的　检测缺氧诱导因子 - 1(HIF- 1)和血管内皮生长因子 (VEGF)与结直肠癌临床病理及预后的关系。方法　用免疫组化 SP法检测 6 1例结直肠癌组织中 HIF- 1α及 VEGF蛋白的表达。结果　结直肠癌组织中HIF- 1α蛋白呈高表达 ,阳性率为 6 5 .6 % ,癌旁及正常组织不表达 ,HIF- 1α与结直肠癌的浸润深度及淋巴结转移密切相关 (P<0 .0 1) ,与 Dukes分期呈正相关 (P<0 .0 1) ;结直肠癌 VEGF阳性表达率为 4 9.2 % ,癌旁及正常黏膜几乎不表达 VEGF,癌间质血管内皮细胞不表达或弱表达 ,VEGF与结直肠癌的浸润深度及淋巴结转移相关(P<0 .0 5 ) ,与 Dukes分期呈正相关 (P<0 .0 2 ) ,且 VEGF阳性表达与 HIF- 1α阳性表达程度呈正相关 (P<0 .0 0 1)。结论　 HIF- 1α与 VEGF在结直肠癌浸润、转移过程中有协同作用 ,同时检测 HIF- 1α、VEGF蛋白的表达可作为判断结直肠癌浸润、转移和预后等生物学行为的重要参考指标     

癌基因C-erbB-2在结直肠癌中的表达及其与浸润转移的相关性

目的:探讨癌基因C-erbB-2在结直肠癌中的表达及其与局部浸润和淋巴结转移的相关性.方法:采用免疫组化SP法检测69例原发性结直肠癌患者根治性手术切除的癌组织及周围组织中C-erbB-2的表达.结果:C-erbB-2基因主要为细胞膜及胞质内表达.结直肠癌组织中C-erbB-2阳性表达率为65.2%(45/69),而在结直肠良性肿瘤中仅有2例表达(2/20),两者存在显著差异(P<0.01);其阳性表达率在结直肠癌组织(65.2%)及周围组织(系膜组织47.8%、癌旁组织30.4%、远端切缘组织13.0%)中有显著差异(P<0.05);其表达与肿瘤大体类型、肿瘤细胞分化程度、临床分期(Dukes分期)及淋巴结转移关系密切(P<0.05),而与结直肠癌患者年龄、性别、肿瘤部位及大小和远处转移无明显关系(P>0.05);C-erbB-2在系膜组织及癌旁组织中的表达证实免疫组织化学方法同常规病理检测比较有显著差异(P<0.05).结论:C-erbB-2在结直肠癌中阳性表达与肿瘤浸润转移密切相关,可作为预测预后的指标.     

整合素β3表达与结直肠癌淋巴结转移的相关性

目的探讨结直肠癌患者肺转移重要的血管内皮细胞标志物整合素β3（ITGB3）表达与结直肠癌转移之间的相关性。 方法采用免疫组织化学染色法检测49例原发性结直肠癌患者癌组织、癌旁正常肠黏膜组织以及相应淋巴结组织中ITGB3的表达。其中37例患者有淋巴结转移。分析ITGB3表达与患者结直肠癌转移的相关性。 结果免疫组化染色结果显示,ITGB3主要在原发性结直肠癌组织、癌旁正常肠黏膜细胞质以及相应淋巴结的间质中表达。ITGB3在不同组织的表达不同,在癌组织中的表达低于癌旁正常肠黏膜组织,且差异有统计学意义（P<0.01）;有淋巴结转移患者淋巴结ITGB3表达高于无淋巴结转移患者,且差异有统计学意义（P<0.001）。淋巴结上皮细胞ITGB3的表达与淋巴结间质组织的表达呈正相关（r=0.395,P=0.005）;且有淋巴结转移患者癌组织上皮细胞ITGB3表达与淋巴结上皮细胞ITGB3表达呈正相关（r=0.514,P=0.001）。ITGB3在淋巴结表达、上皮细胞表达以及间质表达均与淋巴结转移呈正相关（r=0.659,P<0.0001;r=0.661,P<0.0001;r=0.354,P=0.013）。 结论ITGB3淋巴结表达与结直肠癌淋巴结转移呈正相关。ITGB3可能是原发性结直肠癌患者淋巴结转移的潜在分子标志物。     

结直肠癌组织中转化生长因子β表达的意义

目的:探讨结直肠癌组织中转化生长因子(Transforming growth factor,TGF)-β1,2和3的表达及其与临床生物学行为的关系.方法:采用免疫组织化学技术SP法检测67例结直肠癌组织和10例正常黏膜中TGF-β1,2和3的表达.结果:TGF-β1和TGF-β2在结直肠癌组织中的表达明显高于正常黏膜(P＜0.05);结直肠癌中TGF-β1的表达与肿瘤的浸润深度、淋巴结转移和Dukes分期呈正相关(P＜0.05),TGFβ-2仅与肿瘤的Dukes分期有关(P＜0.05),而与肿瘤的浸润深度和淋巴结转移无关(P＞0.05),TGF-β3与肿瘤的浸润深度、淋巴结转移和Dukes分期无相关性(P＞0.05).结论:TGF-β1和TGF-β2可能在结直肠癌的发生中起着重要作用,可反映为结直肠癌的临床生物学行为.     

环氧化酶-2/前列腺素E_2在结直肠癌中的表达及临床意义

目的探讨环氧化酶-2(COX-2)、前列腺素E_2(PGE2)在结直肠癌中的表达及其与结直肠癌临床特征的关系。方法选取2009年8月1日-2012年8月1日于河北北方学院附属医院经病理检查确诊为结直肠癌78例患者的组织标本。免疫组化染色检测COX-2和PGE2的表达,并分析其与患者临床病理学特征的关系。结果结直肠癌组织中COX-2阳性表达率显著增加,与肿瘤大小、分化程度、浸润深度、淋巴结转移和Dukes分期相关;结直肠癌组织中PGE2阳性表达率显著增加,与肿瘤的分化程度、浸润深度、淋巴结转移和Dukes分期相关。Pearson相关分析表明,COX-2与PGE2在结直肠癌组织中的阳性表达显著正相关。结论COX-2、PGE2与结直肠癌的浸润、侵袭和转移密切相关。     

Mad2 and p27 expression profiles in colorectal cancer and its clinical significance

AIM: To investigate the expression of tumor suppressor gene p27 and spindle checkpoint gene Mad2 and to demonstrate their expression difference in colorectal cancer and normal mucosa and to evaluate its clinical significance. METHODS: Immunohistochemical staining was used for detection of expression of Mad2 and p27 in colorectal cancer and its corresponding normal mucosa. RESULTS: Mad2 was significantly overexpressed in colorectal cancer compared with corresponding normal mucosa (P<0.01, chi(2) = 7.5), and it was related to the differentiation of adenocarcinoma, lymph node metastasis and survival period after excision (P<0.05, chi(2) = 7.72, chi(2) = 4.302, chi(2) = 6.234). The rate of p27 positive expression in adenocarcinomas and normal mucosa was 40% and 80% respectively. There was a significant difference in p27 expression between adenocarcinomas and normal mucosa (P<0.001, chi(2) = 13.333), which was related to the differentiation degree of adenoca rcinoma and lymph node metastasis (P<0.05, chi(2) = 8.901 chi(2) = 4). The positive expression of p27 was not correlated with survival period after excision. CONCLUSION: Defect of spindle checkpoint gene Mad2 and mutation of p27 gene are involved mainly in colorectal carcinogenesis and associated with prognosis of colorectal cancer.     

CCR2在结直肠癌的表达及意义

目的探讨大肠癌中CCR2蛋白的表达与肿瘤病理特征的关系。方法用免疫组织化学方法检测148例大肠癌患者手术切除大肠癌组织及66例癌旁对照组织中CCR2表达情况。结果大肠癌组织中CCR2的表达明显高于大肠正常组织（P〈0．01）,并且其表达强度与DukeC＋D期、肿瘤淋巴结转移、远处脏器转移以及较低的分化程度有关（各组中P〈0．01,差异具有统计学意义）;与年龄、性别、肿瘤发生部位以及肿瘤大小无关。结论CCR2的过表达在大肠癌发生、发展及转移的过程中可能发挥一定作用。CCR2可以作为大肠癌分化程度较低且伴淋巴结转移、肝转移的预测指标之一。     

癌组织中VEGF-C及nm23基因蛋白表达与大肠癌浸润转移的关系

目的 探讨血管内皮生长因子c(VEGF-C)及nm23基因蛋白在大肠癌组织中的表达及其与癌局部浸润、淋巴结转移的关系。方法 采用免疫组化SP法,检测93例原发性大肠癌患者手术切除的癌组织中VEGF-C及nm23基因蛋白。结果 VEGF-C基因蛋白阳性表达率与大肠癌组织的分化程度无明显相关性(P>0.05),与癌的浸润深度、淋巴结转移呈正相关(P均<0.05)。nm23基因蛋白在大肠癌淋巴结无转移组中的阳性表达率显著高于有转移组(P<0.05)。结论 VEGF-C及nm23基因蛋白的异常表达在大肠癌的发生、发展和淋巴结转移中可能起重要作用。联合检测癌组织中VEGF-C及nm23基因蛋白,对判断大肠癌的临床分期、淋巴结转移及预后有一定的参考价值。     

Vascular endothelial growth factor-C (VEGF-C) is a more specific risk factor for lymph node metastasis than VEGF-D in submucosal colorectal cancer

BACKGROUND/AIMS: It is useful to decide whether lymphatic involvement or lymph node metastasis exists before polypectomy or operation in submucosal colorectal cancer. Whether vascular endothelial growth factor-C (VEGF-C) or VEGF-D could predict lymph node metastasis and lymphatic involvement is uncertain. METHODOLOGY: Expression of the VEGF-C and VEGF-D in human submucosal colorectal cancers was investigated in paraffin-embedded stepwise sections by means of immunohistochemistry, and the correlation between immunohistochemical expression pattern and clinicopathological features was also evaluated. RESULTS: The results showed that VEGF-C overexpression correlated with lymphatic involvement (P = 0.01) and lymph node metastasis (P = 0.02), but VEGF-D overexpression did not correlate significantly. In multivariate analysis lymphatic invasion was the predictive factor (P = 0.0129), but VEGF-C positivity was not predictive (P = 0.3437). CONCLUSIONS: These results may suggest that VEGF-C is a more specific risk factor for lymph node metastasis than VEGF-D in submucosal colorectal cancer.     

基于Oncomine及TCGA数据集分析结肠肿瘤中HMGB1基因的表达及预后价值

目的研究结肠肿瘤中高迁移率族蛋白B1基因（HMGB1）的差异表达及预后价值。 方法从Oncomine及TCGA数据集中筛选出2 191例结肠肿瘤患者HMGB1基因表达数据及临床病理数据,采用Mann-Whitney U检验比较结肠癌与腺瘤、左半结肠癌与右半结肠癌、原位癌与浸润癌、黏液性腺癌与其他病理类型结肠癌、以及发生淋巴结转移与无淋巴结转移、发生远处转移与无远处转移结肠癌组织中HMGB1基因差异表达情况,并绘制Kaplan-Meier生存曲线。 结果HMGB1基因在结肠癌组织和腺瘤组织中均较正常结肠组织高表达（P<0.001）,在结肠癌组织中较结肠腺瘤组织中高表达,在左半结肠癌组织中较右半结肠癌高表达（P<0.05）,在黏液性腺癌组织中较其他病理类型低表达（P<0.05）,在浸润癌组织中较原位癌高表达（P<0.001）。有淋巴结转移及远处转移者较未转移者高表达（P<0.05）。HMGB1基因高表达提示更高的5年生存率（P=0.011）,尤其对于女性结肠癌患者（P=0.006）。 结论HMGB1基因可作为判断结肠癌浸润深度、淋巴转移、远处转移及预后的标志物。     

CCR7和L-选择素在大肠癌组织中的表达及意义

目的探讨CC趋化因子受体7(CCR7)和黏附分子L-选择素在大肠癌组织中的表达及二者与大肠癌淋巴转移的关系。方法采用免疫组织化学方法检测63份大肠癌组织(大肠癌组)、44份癌旁正常组织(癌旁组)和31份转移灶组织(转移组)中CCR7和L-选择素的表达。结果大肠癌组、转移组CCR7、L-选择素阳性率明显高于癌旁组(P<0.01);CCR7与L-选择素表达显著相关(r=0.653,P<0.01);有淋巴结转移者明显高于无转移者,P<0.05。结论 CCR7与L-选择素在大肠癌中的表达与大肠癌的发生和淋巴转移有关,二者可能共同参与了大肠癌发生及淋巴结转移过程;检测二者表达情况有助于判断大肠癌患者的预后。     

CCL2表达与同时性结直肠癌肝转移的相关性分析

目的观察结直肠癌原发瘤CCL2表达与同时性结直肠癌肝转移的相关性。 方法检索1999年1月至2003年12月中国医学科学院肿瘤医院临床病理资料完整的结直肠癌病例,最终197例纳入研究。其中对照组104例,同时性肝转移组93例。对照病例定义为结直肠癌术后随访5年以上没有复发转移者。采用免疫组织化学法检测结直肠癌原发瘤CCL2表达,单因素和多因素分析CCL2和临床病理因素与结直肠癌肝转移的相关性。 结果多因素分析显示,肿瘤大小、淋巴结分期、CEA和CCL2表达是预示结直肠癌肝转移的独立危险因素(P<0.05),CCL2高表达者肝转移风险是低表达者的5.828倍(95% CI：2.212～15.355)。CCL2与其他临床病理因素的相关性分析表明,CCL2表达仅与肝转移相关(P<0.05),与肿瘤浸润深度、淋巴结分期和CEA均未见统计学差异(P>0.05)。 结论同时性结直肠癌肝转移与肿瘤大小、淋巴结分期、CEA和CCL2表达密切相关。结直肠癌肝转移中CCL2的作用机制可能与常见临床病理因素不同。     

Relationship between indoleamine 2,3-dioxygenase activity and lymphatic invasion propensity of colorectal carcinoma

AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion(LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan(Trp) and kynurenine(Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologicallyand were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups(both p 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp(r = 0.450, p 0.01). Urinary biopterin was significantly higher in cancer cases(p 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients(p 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group(44.56% ± 6.11%) than negative colorectal cancer patients(24.04% ± 6.90%),(p 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis(p 0.01 and p 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients.CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.     

Location of Early Colorectal Cancers at Fold-Top May Reduce the Risk of Lymph Node Metastasis

Purpose This study was designed to look for significant correlations between location of early colorectal cancer, distance from muscularis mucosae to muscularis propria, and the frequency of lymph node metastasis. Methods A total of 166 early colorectal cancers, including 67 surgically resected lesions, were evaluated. The cancers were divided into two groups: metastatic and nonmetastatic. Cancer lesions were further subtyped at the fold-top or fold-bottom. Macroscopic classifications and histology were performed. Absolute invasive depth and distance from muscularis mucosae to muscularis propria was measured. Multivariate analysis was used to assess relationships among the variables. Results The percentage of polypoid cancer lesions at fold-bottom was higher than at fold-top (74.5 vs. 51.8 percent), whereas flat-type cancer lesions at fold-bottom occurred less often than at fold-top (8.2 vs. 30.4 percent). Logistic regression showed that deep absolute invasive depth, lymphatic and vessel invasion, and cancer location (at fold-bottom) were the significant risk factors for early colorectal cancers leading to lymph-node metastasis. The distance from muscularis mucosae to muscularis propria with lymph-node metastasis (1,396.7 ± 728.4 μm) was shorter than without lymph-node metastasis (3,533.9 ± 2,507.8 μm; P < 0.01). Multivariate analysis showed that distance from muscularis mucosae to muscularis propria was a statistically significant factor for early colorectal cancers leading to lymph node metastasis (P = 0.0054). Conclusions We conclude that early colorectal cancers at the fold-top or with a long distance from muscularis mucosae to muscularis propria have less tendency to metastasize to lymph nodes. Clinically, these results provide evidence of a new indicator of endoscopic mucosal resection for early colorectal cancers at the fold-top.