Stathmin及Cathepsin B在结直肠癌中的表达

目的研究Stathmin和Cathepsin B在人结直肠癌组织及其转移灶中的表达差异,探讨Stathmin和Cathepsin B在结直肠癌发生发展过程中的作用及其临床病理意义。 方法用免疫组织化学染色技术检测158例高分化,中分化及低分化结直肠癌患者手术切除标本及64例相应转移灶组织中Stathmin蛋白和Cathepsin B蛋白的表达情况。 结果Stathmin蛋白及Cathepsin B蛋白在结直肠癌组织及其转移灶中均高表达(分别为P<0.05及P<0.01);高分化结直肠癌样本中Stathmin蛋白及Cathepsin B蛋白在细胞膜或细胞浆阳性表达,而在低分化结直肠癌细胞核,细胞膜及细胞浆中可见二者的阳性表达。 结论Stathmin及Cathepsin B可能是判断结直肠癌患者临床病理分级的有用指标。     

CXCL13及其受体CXCR5与结直肠癌转移及KRAS基因突变关系的探讨

目的观察趋化因子CXCL13及其受体CXCR5在结直肠癌转移灶中的表达变化,探讨其与结直肠癌转移及KRAS基因突变的关系。方法选择97例结直肠癌组织标本（观察A组）、51例淋巴结转移灶标本（观察B组）,同时选择52例正常结直肠标本（对照A组）和43例正常淋巴结标本（对照B组）。用免疫组织化学法检测CXCL13及CXCR5蛋白在上述组织中的表达,分析其与临床病理参数、患者生存时间之间的关系。用Real Time PCR法检测148例结直肠癌组织KRAS基因突变情况,并分析其与CXCL13及CXCR5蛋白表达的关系。结果CXCR5在上皮细胞的表达率较高,CXCL13在间质细胞的表达较高。CXCL13及其受体CXCR5蛋白在结直肠癌组织的表达高于正常组织（P〈0.05）,在转移淋巴结中的表达明显高于正常淋巴结（P〈0.05）。在结直肠癌原发灶和淋巴结转移灶中,CXCL13及其受体CXCR5蛋白的表达均具有明显的相关性（P〈0.05）。在CXCL13及其受体CXCR5表达的患者中,其中位生存时间明显短于其阴性表达者（P均〈0.05）。观察A组KRAS基因突变型36例（其中CXCL13表达阳性12例、CXCR5表达阳性17例）,野生型61例（其中CXCL13表达阳性23例、CXCR5表达阳性23例）,CXCL13及CXCR5蛋白表达与KRAS基因是否发生突变均有相关性（P均〈0.05）。观察B组KRAS基因突变型20例（其中CXCL13表达阳性16例、CXCR5表达阳性14例）,野生型31例（其中CXCL13表达阳性8例、CXCR5表达阳性11例）,CXCL13及CXCR5蛋白表达与KRAS基因是否发生突变均有相关性（P均〈0.05）。结论趋化因子CXCL13及其受体CXCR5蛋白在结直肠组织淋巴细胞的归巢及结直肠癌淋巴结的转移中发挥重要的作用,对预测结直肠癌的转移及评估预后有一定的价值。CXCL13及CXCR5蛋白表达与KRAS基因突变具有较高的一致性。     

Runx3和C-myc基因在结直肠癌组织中的表达及临床意义

目的探讨Runx3和C-myc在结直肠癌组织中的表达及其临床意义。方法 Western免疫印迹法检测63例结直肠癌病人的癌组织及相应癌旁正常组织(距癌缘>5 cm)中Runx3蛋白和C-myc蛋白的表达水平,了解Runx3、C-myc的表达与结直肠癌患者主要临床病理参数之间的相关性。结果 Runx3在结直肠癌组织中的表达下调,C-myc在结直肠癌组织中的表达上调,二者的表达呈负相关(r=-0.398,P=0.001),且其各自的表达在不同Dukes分期、肿瘤浸润深度、淋巴结转移状态及病理分化类型的差异均具有统计学意义(P<0.05),临床分期越晚、病理分化越低,Runx3表达下调、C-myc表达上调越明显。结论①Runx3在大多数结直肠癌组织中的表达下调,可能参与了结直肠癌的侵袭和转移。②C-myc在大多数结直肠癌组织中的表达上调,可能与细胞增殖和分化有关。③Runx3基因表达下调,可能影响C-myc基因表达增强,从而与结直肠癌的发生发展有着密切关系。     

SHP-2在结直肠癌组织中的表达及临床意义

目的探讨SHP-2蛋白在结直肠癌中的表达情况及其与病理特征的关系.方法采用免疫组织化学法和Western blot方法检测SHP-2蛋白在人结直肠癌组织中的表达情况,分析其与患者临床病理因素的关系.结果结直肠癌组织中S H P-2阳性表达率为25.6%(43/168),与正常结直肠组织比较,差异有统计学意义(P0.05).结直肠癌组织中SHP-2的蛋白水平为0.2396±0.0655,与配对正常结直肠组织比较(0.7665±0.1133),差异有统计学意义(P0.0001).SHP-2蛋白的低表达与分化程度和淋巴结转移有关,与性别、年龄、浸润程度、远处转移、TNM分期无关.结论SHP-2可能在结直肠癌的发生发展过程中起抑制作用,并可能成为潜在的治疗靶点.     

结直肠癌组织间质细胞中CD10蛋白的表达变化及临床意义

目的观察CD10蛋白在结直肠癌组织间质细胞中的表达情况,探讨其在结直肠癌发生、发展中的作用。方法同期手术留取的80份结直肠癌组织及50份癌旁正常结肠黏膜组织,采用快捷免疫组化Max、Vision“法检测两者间质细胞中CD10蛋白表达情况,并分析阳性表达率与结直肠癌临床病理特征的关系。结果CD10蛋白在结直肠癌组织和正常结肠黏膜组织问质细胞中的阳性表达率分别为70．00％（56/80）、0,差异有统计学意义（P〈0．01）;结直肠癌组织间质细胞中CD10蛋白表达与患者性别、年龄、肿瘤部位、临床分期无关（P均〉0．05）,而与肿瘤细胞的分化程度、浸润深度、有无脉管侵犯及淋巴结转移有关（P均〈0．05）。结论CD10蛋白在结直肠癌组织间质细胞中呈高表达,可能与肿瘤的发生、发展及浸润转移有关。     

Livin和Caspase-3在结直肠癌组织中的表达及其相关性

目的确定Livin蛋白和Caspase-3蛋白在结直肠癌组织细胞中的定位,并分析其与临床病理特征的相关性。方法应用免疫组化技术检测Livin蛋白和Caspase-3蛋白。结果结直肠癌组织Livin高表达,同时Caspase-3低表达;正常大肠组织及结肠腺瘤息肉中无Livin表达,而Caspase-3高表达。Livin蛋白定位于细胞质中;Caspase-3蛋白绝大多数定位于细胞质,极少数定位于细胞核中。结论 Livin基因激活与结直肠癌发生、发展相关,促凋亡基因Caspase-3与凋亡抑制基因Livin共同调节参与了结直肠癌的发病机制。Livin蛋白的表达与结直肠癌分化程度明显相关,分化越低,表达越高;与结直肠癌的临床分期、淋巴转移无关。     

Diversin在结直肠癌中表达及与临床病理因素的关系

目的研究Diversin在结直肠癌组织中的表达及与临床病理因素的关系。方法收集沈阳医学院附属中心医院病理科结直肠癌蜡块组织51例及配对的癌旁组织,采用EnVision两步法检测Diversin在结直肠癌组织及癌旁组织中的免疫组织化学表达。结果 Diversin在结直肠癌组织阳性表达率(80.39%)明显高于癌旁组织(9.80%),且Diversin在不同分化程度,临床分级,淋巴结转移的结直肠癌患者中差异有统计学意义(P0.05)。结论 Diversin在结直肠癌中高表达,并且与结直肠癌患者的分化程度、临床分级、淋巴结转移有关,可能成为结直肠癌诊治的生物学标记物。     

黏蛋白1表达与β-连环蛋白异位在结直肠癌中的临床意义

目的探讨黏蛋白1(mucin 1,MUC1)表达与β-连环蛋白(β-catenin)异位在结直肠癌中的临床意义。方法选取67例结直肠癌患者手术切除组织石蜡标本纳入本研究,采用免疫组化染色检测MUC1和β-catenin的表达情况,并确定标本MUC1阳性表达率和β-catenin异位阳性率。进一步分析MUC1阳性表达率和β-catenin异位阳性率对患者临床病理特征的影响,及MUC1阳性表达和β-catenin异位的相关性。结果 MUC1的表达不再局限于肠上皮细胞面向腔道的顶端细胞膜,而是向全细胞扩散,并在胞浆中出现,与癌周组织比较,MUC1阳性表达率显著增加,并影响肿瘤的分化程度和淋巴结转移;癌组织中β-catenin表达向胞浆,甚至细胞核异位。β-catenin异位表达显著影响肿瘤的分化、浸润和淋巴结转移。MUC1表达与β-catenin异位的相关分析显示,两者呈密切正相关。结论 MUC1可通过β-catenin异位参与结直肠癌患者不良预后的进展过程。     

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。     

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.     

Sialoglycoconjugate expression in primary colorectal cancer and metastatic lymph node tissues

BACKGROUND/AIMS: Aberrant cell surface glycosylation, and especially excessive sialylation, is thought to have great importance in tumor malignancy. To investigate the clinicopathological significance of sialylation in colorectal cancer, we performed histochemical analyses using sialic acid-binding lectins. METHODOLOGY: Primary colorectal cancer and lymph node tissues obtained from 80 cases were subjected to lectin-immunohistochemical staining using Maackia amurensis leukoagglutinin (MAL) and Sambucus nigra agglutinin (SNA). The relationship between the staining characteristics and the various clinicopathological parameters was statistically analyzed. RESULTS: In primary cancer tissues, a high level of SNA staining was significantly related to worse prognosis and some pathological characteristics such as lymph node metastasis, whereas a high level of MAL staining was related to worse prognosis. In metastatic lymph node tissues, positive staining was frequently found for MAL and SNA, which wasremarkable in cases categorized as N2 metastasis. Furthermore, cases with MAL-positive staining in metastatic lymph node tissues evidently indicated worse prognosis than those with MAL-negative staining. CONCLUSIONS: Aberrant expression of SNA-positive sialoglycoconjugates in primary colorectal cancer tissues is important in terms of unfavorable pathological characteristics of the cancer. In addition, aberrant expression of MAL-positive sialoglycoconjugates in metastatic lymph node tissues might be related to worse prognosis.     

High level of ezrin expression in colorectal cancer tissues is closely related to tumor malignancy

AIM： To investigate the ezrin expression in normal colorectal mucosa and colorectal cancer tissues, and study the correlation between ezrin expression in colorectal cancer tissues and tumor invasion and metastasis. METHODS： Eighty paraffin-embedded cancer tissue samples were selected from primary colorectal adenocarcinoma. Twenty-eight patients had well- differentiated, 22 had moderately differentiated and 30 had poorly differentiated adenocarcinoma. Forty-five patients and 35 patients had lymph node metastasis. Forty-five patients were of Dukes A to B stage, and 35 were of C to D stage. Another 22 paraffin-embedded tissue blocks of normal colorectal epithelium （〉 5 cm away from the edge of the tumor） were selected as the control group. All patients with colorectal cancer were treated surgically and diagnosed histologically, without preoperative chemotherapy or radiotherapy. The immunohistochemistry was used to detect the ezrin expression in paraffin-embedded normal colorectal mucosa tissues and colorectal cancer tissue samples. RESULTS： Ezrin expression in colorectal cancer was significantly higher than in normal colorectal mucosa （75.00% vs 9.09%, P 〈 0.01）, and there was a close relationship between ezrin expression and the degree of tumor differentiation, lymph node metastasis and Dukes stage （88.46% vs 50.00%, P 〈 0.01; 94.28% vs 51.11%, P 〈 0.01; 94.28% vs 51.11%, P 〈 0.01）. CONCLUSION： Ezrin expression is obviously higher in colorectal cancer tissues than in normal colorectal mucosa tissues, and the high level of ezrin expression is closely related to the colorectal cancer invasion and metastasis process.     

Comparative study of proteome between primary cancer and hepatic metastatic tumor in colorectal cancer

AIM: To identify the differential proteins associated with colorectal cancer genesis and hepatic metastasis.METHODS: Hydrophobic protein samples were extracted from normal colorectal mucosa, primary cancer lesion and hepatic metastatic foci of colorectal cancer. With twodimensional electrophoresis and image analysis,differentially expressed protein spots were detected, and the proteins were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and peptide mass fingerprint analysis.RESULTS: Significant alterations of the proteins in number and expression levels were discovered in primary cancer and hepatic metastatic foci, the expression of a number of proteins was lost in 25-40 ku, but protein spots was increased in 14-21ku, compared with normal mucosa. Nine differentially expressed protein spots were identified. Three proteins expressed in normal mucosa, but lost in primary cancer and hepatic metastasis, were recognized as calmodulin, ribonuclease 6 precursor and mannosidase-α.Proapolipoprotein was expressed progressively from normal mucosa to primary cancer and hepatic metastasis. The differentially expressed protein of beta-globin was found in normal mucosa and hepatic metastatic tumor, but lost in primary cancer lesion. Cdc 42, a GTP-binding protein, was identified in hepatic metastasis. The protein spots of C4 from primary cancer, M7 and M9 from hepatic metastasis had less homology with the proteins in database.CONCLUSION: Variations of hydrophobic protein expression in colorectal cancer initiation and hepatic metastasis are significant and can be observed with two-dimensional electrophoresis. The expression of calmodulin, ribonuclease 6 precursor and mannosidase-α is lost but the expression of proapolipoprotein is enhanced which is associated with colorectal cancer genesis and hepatic metastasis. Cdc 42 and beta-globin are expressed abnormally in hepatic metastasis. Protein C4, M7 and M9 may be associated with colorectal cancer genesis and hepatic metastasis.     

生物钟基因hClock蛋白在结直肠肿瘤中的表达研究

目的探讨人类生物钟基因hClock蛋白在结直肠肿瘤中的表达及其意义。方法应用免疫组织化学法检测不同Dukes分期结直肠肿瘤及相应癌旁组织中hClock基因蛋白产物（Clock蛋白）的表达，并比较其差异。结果Clock蛋白红结直肠肿瘤中呈现中或强阳性表达，与肿瘤分化程度及Dukes分期无显著相关性（P〉0.05）。癌旁组织呈现弱阳性表达。结论Clock蛋白与结直肠肿瘤的发生有相关性，与侵袭、转移的关系有待更深入地研究。     

Expression of heat shock protein 70 (HSP70) in patients with colorectal adenocarcinoma--immunohistochemistry and Western blot analysis

The role of heat shock protein 70 (HSP70) expression has been investigated in various types of tumors. There are only little and controversial data about its clinical relevance in colorectal carcinoma, one of the most common carcinomas observed in humans. In this study we investigated expression of HSP70 in human colonic carcinoma and possible correlation with clinicopathology. To assess patterns (cytosolic and membrane) of HSP70 expression, the 48 surgically removed colorectal adenocarcinomas and 12 normal colonic and rectal mucosal samples were examined by immunohistochemistry and Western-blot. According to results of immunohistochemistry, expression of cytoplasmic HSP72 was significantly higher in colorectal carcinoma compared with normal and adjacent mucosa (p<0.01). In addition, there was significant increase in HSP72 expression in lymph node-positive compared to node-negative group (p<0.001). Dukes C2 stage of colonic cancer showed significantly higher immunohistochemical score than Dukes B2 and B1 stage groups (p< 0.05 i.e. p< 0.02). There was no relation between expression of HSP72 and degree of tumor differentiation. Using Western blot analyses, we noticed elevated levels of cytosolic HSP70 in colorectal cancer cells compared to normal. Densitometric analysis of blots of plasma membrane HSP70 expression has shown decrease in colorectal cancer cells compared to normal mucosa. According to our results, overexpression of HSP72 in malignant tissues of patients with colorectal carcinoma is related to tumor progression, suggesting that these proteins could play an important role not only in tumorigenesis but also in the development of drug resistance. Further research is necessary to clarify the mechanisms responsible for differential HSP70 expression as well as its definitive role in colorectal cancer.     

内皮抑素和血管抑素表达与大肠肿瘤侵袭转移的关系

目的探讨内皮抑素和血管抑素在大肠肿瘤组织中的表达,与大肠癌不同阶段的关系及临床意义。方法应用免疫组织法检测20例正常大肠组织、20例大肠腺瘤和60例大肠癌及其组织中内皮抑素和血管抑素的表达情况。应用χ2检验对内皮抑素和血管抑素两者在大肠肿瘤不同阶段的表达关系进行统计分析,两者表达间的相关性探讨采用spearman相关分析。结果内皮抑素和血管抑素阳性表达与大肠肿瘤不同阶段的关系spearman相关系数分别为-0.438、-0.362,两者的表达与大肠癌的Dukes分期、淋巴结转移显著相关(P<0.05),均与腺瘤的类型无相关性。结论内皮抑素和血管抑素可以抑制大肠癌的侵袭转移。内皮抑素和血管抑素在大肠癌组织中呈低表达,且两者的阳性表达率随着临床分期的进展而降低,提示其与大肠癌的发生、发展、浸润及转移有明显关系。两者在大肠癌组织中的表达呈明显的一致性,对两者进行联合检测,有助于大肠癌的早期诊断、治疗及预后的评估。     

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。     

老年贲门癌组织中caspase-3表达及其临床意义

目的研究半胱氨酸天冬氨酸蛋白酶3(caspase-3)表达在老年贲门癌发生发展中的作用。方法采用免疫组化S-P法观察113例老年贲门癌旁上皮细胞、原发癌细胞和浸润淋巴细胞以及转移灶癌细胞中caspase-3表达,并分析原发灶癌细胞caspase-3表达与贲门癌临床病理特征的关系。结果caspase-3在贲门癌旁上皮细胞中的表达高于原发灶癌细胞(P<0·05);caspase-3在贲门癌原发灶浸润淋巴细胞中的阳性率高于贲门癌旁上皮细胞和原发灶癌细胞(P<0·05);转移灶癌细胞中caspase-3阳性率高于原发灶癌细胞(P<0·05);原发灶癌细胞中caspase-3表达与贲门癌患者的年龄、性别以及贲门癌肿瘤大小、浸润深度、转移、TNM分期、生长方式和分化程度无相关性(P<0·05)。结论贲门癌原发灶癌细胞caspase-3表达下调和浸润淋巴细胞caspase-3表达上调与贲门癌发生有关,来自原发灶和转移微环境中的化学物质可能通过提高转移灶癌细胞中caspase-3表达,进而起到抑制转移灶的作用。     

Transforming growth factor—β1in invasion and metastasis in colorectal cancer

AIM：To investigate the role of TGFβ1 in invasion and metastasis in colorectal cancer by analysing TGFβ1 correlated wity depth of tumor invasion,stage and metastasis.METHODS:Serum TGFβ1levels were determined in50patients with colorectal cancer and 30healthy volunteers using a TGFβ1 enzyme-linked immunosorbent assay.TGFβ1 expression in primary and lymph node metastatic lesions were detected in 98cases of colorectal cancer by immunohistochemical staining and in situ hybridization.RESULTS:Serum levels of TGFβ1 in patients with colorectal cancer(40&#177;18μg&#183;L^-1)were significantly higher than those in the healthy control group(19&#177;8μg&#183;L^-1),P&lt;0.05.Elevated levels of serum TGFβ1were found in 60%of patients with colorectal cancer when the mean+2s was used as the upper limit of the normal range(35.1μg&#183;L^-1).Increases in serum TGFβ1 levels were significantly asociated with Dukei‘s stage(P&lt;0.05),but there was no significant difference between,Duki‘s stage Bpatients and Dukei‘s stage Cpatients.In the cytoplasm of cancer cells,TGFβ1 was immunostained in37.8%(37/98)of colorectal cancer,and this expression was confirmed by in situ hybridization,Among35cases of colorectal cancer with lymph node metastatic lesions,TGFβ1 positive staining was found in18(51.4%)cases of primary tumor,and 25(71.4%)cases with lymph node metastatic lesions,respectively,Of17cases with no staining in the primary lesion.7(41.2%)casesshowed TGFβ1 staining in the metastatic lesion.Serum TGFβ1 levels and TGFβ1 expression in colorectal cancer tissues were correlated significantly with depth of tumor invasion,stage and metastasis,Patients in stage C-D,T3-T4and with metastasis had significantly higher TGFβ1 levels than patients in stage A-B,T1-T2and without metastasis(P&lt;0.05).CONCLUSION:These results suggest that transforming growth factor-β1 is closely related to the invasion and metastasis of colorectal cancer.It increased the invasive and metastatic potential of tumor by altering a tumor microenvironment.TGFβ1 may be used as a possible biomarke.