泛素、Skp2、p27在大肠癌组织中的表达及意义

采用组织芯片技术制作80例大肠癌癌组织芯片。S-P免疫组织化学方法检测芯片中泛素、S期激酶相关蛋白2（Skp2）和p27表达。结果泛素表达阳性率为45．0％，Skp2阳性率为47．5％，p27阳性率为38．8％，不同组织学类型大肠癌中泛素、skp2、p27的表达未见明显差异（P〉0．05）；有淋巴结转移者Skp2阳性率显著高于无淋巴结转移者（P〈0．01），p27阳性率显著低于无淋巴结转移者（P〈0．01）。提示Skp2高表达和p27低表达与大肠癌的进展相关，Skp2和p27的表达可以作为评估大肠癌预后的参考指标；泛素和Skp2在p27的表达调控中起重要作用；应用组织芯片大规模高效检测临床组织样本是可行的，具有快速、方便、经济、准确的特点。     

结直肠腺癌中skp2、p27^kip1、ERK蛋白的表达及意义

目的研究细胞S期激酶相关蛋白2（skp2）、p27k ip1、细胞外调节蛋白激酶（ERK）蛋白在结直肠癌组织中的表达情况及在结直肠腺癌发生发展中的作用。方法应用免疫组化法检测60例结直肠癌组织（A组）、30例腺瘤组织（B组）、20例正常大肠组织（对照组）中skp2、p27k ip1、ERK蛋白的表达,分析其与临床病理因素的关系。结果 3组skp2、p27k ip1、ERK蛋白表达阳性率比较差异均有统计学意义（P〈0.05）;skp2、p27k ip1、ERK蛋白的表达与结直肠腺癌的分化程度、Dukes’分期及淋巴结转移有关（P〈0.05）;skp2、ERK与p27k ip1表达呈负相关（r=-0.723 7、P〈0.01;r=-0.695 2、P〈0.01）,而skp2与ERK表达呈正相关（r=0.652 2、P〈0.01）。结论 skp2、p27k ip1、ERK蛋白的表达可能与结直肠腺癌的发生发展有关,ERK可能参与了skp2-p27k ip1通路的调节。     

大肠癌组织中Cyelin E、p27kipl和Ki-67的表达及意义

目的采用免疫组化PowerVision两步法检测137例大肠癌及其邻近正常黏膜组织中细胞周期素E（Cyclin E）、抑制因子p27kipl和核抗原-67（Ki-67）。结果：大肠癌组织中Cyclin E表达水平显著高于邻近正常黏膜组织，并与原发肿瘤浸润深度、区域淋巴结转移及TNM分期显著正相关（r分别为0．213、0．367、0．348，P均〈0．05）。大肠癌组织中p27kipl表达水平显著低于邻近正常黏膜组织，并与原发肿瘤浸润深度、区域淋巴结转移及TNM分期显著负相关（r分别为-0．345、-0.269、-0.348，P均〈0.01）。大肠癌组织中Ki-67表达水平显著高于邻近正常黏膜组织，并与区域淋巴结转移及TNM分期呈显著的正相关（r分别为0．218、0．172，P〈0．05）。大肠癌组织中Cyclin E与p27kipl表达水平显著负相关（r=-0．235，P〈0．01）；CycHn E和Ki-67表达水平显著正相关（r=0．243，P〈0．01）；大肠癌组织中p27kipl与Ki-67表达水平呈显著负相关（r=-0．172，P〈0．01）。认为Cyclin E和p27kipl是大肠癌发生及侵袭转移的正、负性因子，联合检测Cyclin E、p27kipl和Ki-67有助于判断大肠癌的生物学行为及预后判断。     

大肠癌组织中p27kipl、MMP-9的表达及临床意义

采用免疫组化SP法检测216例大肠癌组织中p27^kipl和基质金属蛋白酶（MMP）-950表达。p27^kipl阳性表达166例（76．9％）。低表达141例（65．3％），瘤细胞核、质共表达73例（33．8％）；MMP-9阳性表达183例（84．7％），高表达98例（45．4％）。p27^kipl、MMP-9表达与大肠癌分化程度、Dukes分期、患者生存期、淋巴结转移及器官转移密切相关（P均〈0．05）。认为p27^kipl低表达和MMP-9高表达在大肠癌的进展中发挥重要作用，二者可作为判断大肠癌侵袭、转移及预后的生物学指标。     

血管生成素-2与基质金属蛋白酶-7在大肠癌中的表达及意义

目的:研究血管生成素-2(Ang-2)及基质金属蛋白酶-7(MMP-7)蛋白在人大肠癌组织中的表达及其与大肠癌临床病理特征的关系．方法:应用免疫组化法检测40例大肠癌及其癌旁正常组织中Ang-2及MMP-7蛋白表达水平．结果:大肠癌组织中Ang-2蛋白表达阳性率为77．5％(31/40),明显高于癌旁正常组织 40％(16/40)(P=0．001);Ang-2表达水平与患者性别、年龄及癌组织的部位、大小、分化程度、淋巴结转移无关(P>0．05);与浸润深度, 远处转移及Dukes’分期相关(分别为P=0．007, P=0．023,P=0．008);大肠癌组织RMMP-7蛋白表达阳性率为85％(34/40),明显高于癌旁正常组织35％(14/40)(P=0．000)．MMP-7蛋白表达阳性率与Ang-2的表达相关(P=0．016)．结论:Ang-2蛋白可能通过促进MMP-7的表达从而促进了大肠癌的生长及转移．     

子宫内膜腺癌组织中maspin、VEGF-C的表达变化及意义

目的观察子宫内膜腺癌组织中maspin和血管内皮生长因子C（VEGF—C）的表达变化,并探讨其意义。方法采用免疫组化sP法检测49例子宫内膜腺癌（腺癌组）、10例不典型增生（增生组）及15例正常子宫内膜（正常组）组织中的maspin蛋白和VEGF-C。结果腺癌组maspin、VEGF—C蛋白阳性率分别为57．1％、49．0％,增生组分别为40．0％、20．0％,正常组均为0。各组相比,P〈0．05。maspin表达与子宫内膜腺癌病理分期有关（P〈0．05）,VEGF—C表达与子宫内膜腺癌淋巴结转移、组织分级及肌层浸润有关（P均〈0．05）。子宫内膜腺癌组织中maspin、VEGF-C的表达呈正相关（r=0．519,P〈0．05）。结论子宫内膜腺癌组织中maspin、VEGF-C高表达,在子宫内膜腺癌的发生、浸润和转移中起重要作用。     

大肠癌组织中Cyclin E、p27kipl和Ki-67的表达及意义

目的 采用免疫组化PowerVision两步法检测137例大肠癌及其邻近正常黏膜组织中细胞周期素E(Cyclin E)、抑制因子p27kipl和核抗原-67(Ki-67).结果 :大肠癌组织中Cyclin E表达水平显著高于邻近正常黏膜组织,并与原发肿瘤浸润深度、区域淋巴结转移及TNM分期显著正相关(r分别为0.213、0.367、0.348,P均＜0.05).大肠癌组织中p27kipl表达水平显著低于邻近正常黏膜组织,并与原发肿瘤浸润深度、区域淋巴结转移及TNM分期显著负相关(r分别为-0.345、-0.269、-0.348,P均＜0.01).大肠癌组织中Ki-67表达水平显著高于邻近正常黏膜组织,并与区域淋巴结转移及TNM分期呈显著的正相关(r分别为0.218、0.172,P＜0.05).大肠癌组织中Cyclin E与p27kipl表达水平显著负相关(r=-0.235,P＜0.01);Cydin E和Ki-67表达水平显著正相关(r=0.243,P＜0.01);大肠癌组织中p27kipl与Ki-67表达水平呈显著负相关(r=-0.172,P＜0.01).认为Cyclin E和p27kipl是大肠癌发生及侵袭转移的正、负性因子,联合检测Cyclin E、p27kipl和Ki-67有助于判断大肠癌的生物学行为及预后判断.     

RT-PCR寻找大肠癌患者外周血早期分子标记物的研究

目的:探求大肠癌患者早期诊断的外周血分子标记物,为大肠癌临床筛查提供早期、可靠、简便易行的有效方法．方法:采用RT-PCR检测28例大肠癌、8例腺瘤中重度不典型增生、18例腺瘤轻度不典型增生、11例炎性息肉患者和10例正常对照者的外周血中CK-20,GST-π,hTERT,survivin及 skp2的mRNA表达情况．结果:大肠癌、腺瘤中重度不典型增生、腺瘤轻度不典型增生、炎性息肉组和正常对照组hTERT mRNA表达的阳性率分别为 82．1％(23/28)、87．5％(7/8)、27．8％(5/11)、 9．1％(1/11)、10％(1/10),大肠癌组及腺瘤中重度不典型增生组与其他各组之间差别显著 (P<0．05);survivin mRNA在大肠癌、腺瘤中重度不典型增生组、腺瘤轻度不典型增生组的阳性率分别是64．2％(18/28)、50%(4/8)、 11．1％(2/18),炎性息肉组及正常组未见表达, 大肠癌组与腺瘤中重度不典型增生组无差别, 与腺瘤轻度不典型增生组、炎性息肉及正常组之间差别显著(P<0．05);而CK-20,GST-π, skp2 mRNA在各组之间表达无统计学意义(均 P>0．05)．结论:RT-PCR检测大肠癌患者外周血hTERT, survivin mRNA的表达对大肠癌的早期诊断有意义,可望成为早期诊断的分子标记物．     

Fascin、CD_（24）、CD_（73）、Hsp27与大肠癌亲器官转移的相关性探讨

目的观察CD24、CD73、Hsp27和Fascin蛋白在大肠癌组织中的表达,探讨其与大肠癌亲器官转移的相关性及临床病理意义。方法应用免疫组织化学技术检测Fascin、CD24、CD73和Hsp27蛋白在20例无转移大肠癌和19例同时伴有淋巴结和肝脏转移的大肠癌的不同部位癌组织中的表达。结果转移性大肠癌原发灶与未转移大肠癌比较,CD73、Fascin的表达差异显著（P=0.009,0.009）,Hsp27、CD24的表达无明显差异。CD24在淋巴结转移灶的表达与肝转移灶和原发灶比较,差异显著（P=0.000,0.001）;原发灶和肝转移灶的表达比较,差异不显著。CD73肝转移灶的表达与淋巴结转移灶和原发灶比较差异显著（P=0.003,0.000）;而淋巴结转移灶和原发灶的表达比较无明显差异。Hsp27在肝转移灶的表达与原发灶比较,无明显差异;与淋巴结转移灶比较,差异显著（P=0.001）;在原发灶与淋巴结转移灶的表达比较差异显著（P=0.021）。Fascin在原发灶的表达与肝转移灶、淋巴结转移灶比较无明显差异。结论 CD24与大肠癌淋巴结转移相关,可能是大肠癌淋巴结转移的预测因子之一;CD73、Hsp27的高表达与大肠癌肝转移有关,Fascin的表达与大肠癌转移有关,但与大肠癌转移至淋巴结或肝脏无相关性。     

大肠癌组织中P16蛋白和血管内皮生长因子的表达及其临床意义

目的：探讨大肠癌组织中P16蛋白和血管内皮生长因子（VEGF）表达及其临床意认。方法：用S－P免疫组织化学方法测定66例大肠癌组织和20例正常大肠组织中P16蛋白和VEGF的表达。结果：大肠癌中P16蛋白阳性率为48．5％（32／66）明显低于对照组的70．0％（14／20）（P＜0．01），VEGF阳性率为72．7％（48／66）则明显高于对照组的15．0％（3／20）（P＜0．01）：P16蛋白和VEGF在大肠癌中表达具有明显负相关性；P16蛋白和VEGF表达与大肠癌组织学类型、肿瘤直径、肿瘤部位无关（P＞0．05），而与淋巴结转移、Duke's分期五年生存率有明显的关系（P＜0．01）。结论：大肠癌中存在P16蛋白下调和VEGF上调，P16蛋白和VEGF表达可作为反映大肠癌生物学行为的指标之一。     

High expression of skp2 correlates with poor prognosis in endometrial endometrioid adenocarcinoma

Purpose: Skp2 interacts with the degradation of cyclin-dependent kinase inhibitor p27. This study aimed to investigate the correlation of skp2 expression with the expression of p27 and other cell cycle regulators, and clinicopathological parameters in endometrial endometrioid adenocarcinoma. Methods: Tissue samples of 136 endometrioid adenocarcinomas, in addition to 20 endometrial hyperplasias and 20 normal endometria, were immunohistochemically stained for skp2. The expression was represented as a labeling index (LI), which indicates the percentage of positive nuclei. Results: Skp2 staining was localized in the nuclei of the glandular cells of the proliferative phase endometrium, and endometrial hyperplasia and carcinoma cells. Skp2 expression was increased significantly in those of higher histological grade. The high level of skp2 expression was significantly correlated with the presence of lymph node metastasis and lymph-vascular space involvement. The LI of skp2 in endometrial carcinoma was significantly correlated with that of p27, Ki-67, cdk2, cyclin A, cyclin D1, cyclin E, p53 and PTEN. The high level of skp2 expression (LI≧20%) was significantly correlated with the patients’ poor survival. Conclusions: The skp2 level might have increased due to p27 accumulation and may be a good indicator of proliferative activity and poor prognosis.     

P21~(ras)、P16在大肠癌中的表达及临床意义

目的探讨癌基因P21~(ras)及抑癌基因P16与大肠癌的关系。方法应用免疫组化SP法分析、研究了P21~(ras)蛋白、P16蛋白在80例大肠癌、20例大肠腺瘤及20例正常大肠组织中的表达。结果①P21~(ras)在前二者中的阳性表达率分别为70.1％(57/80)和65％(13/20),明显高于在正常组织中的30％(6/20),其比较具有显著性差异(x~2=17.66、P<0.005;x~2=5.23、P<0.05);P16在大肠癌中的阳性表达率为36.3％(29/80)低于在腺瘤及正常组织中的65％(13/20)和75％(15/20),其比较亦具有显著性差异。②P21~(ras)、P16的阳性表达率在大肠癌患者的年龄、性别及肿瘤大小方面无显著性差异,而与肿瘤的临床Dukes分期(x~2=6.20、P<0.025;x~2=6.25、P<0.05)、有无淋巴结转移及术后5a生存率密切相关。③P21~(ras)在不同的大肠癌组织病理类型中,其表达率无显著性差异;P16的阳性表达率随着肿瘤浸润深度的增加有下降趋势,但无统计学意义。④在80例大肠癌患者中,P21~(ras)阳性而P16阴性者比率高于其他三者,而且这类大肠癌患者的术后5a生存率下降。结论大肠癌的发生、发展,是由包括癌基因、抑癌基因在内的多种因素作用的结果;在临床工作中联合检测P21~(ras)及P16蛋白在大肠癌中的表达水平,对我们估计患者的病情、推测其预后有指导性意义。     

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.     

Prognostic significance of maspin expression in human gastric adenocarcinoma

BACKGROUND/AIMS: Maspin is a member of the serpin family of protease inhibitors known to have tumor suppressor activity. However, molecular aspects in carcinogenesis and progression of gastric cancer remain largely unclear. Previously we reported for the first time that maspin is induced in the course of gastric carcinogenesis. In the present study we evaluated maspin induction in gastric adenocarcinoma in relation to a number of clinicopathologic feature. METHODOLOGY: Maspin expression was examined by Western blot analysis and immunohistochemical staining in 82 cases of gastric adenocarcinoma. RESULTS: In Western blot analysis, gastric specimens of tumor showed increased maspin expression compared with corresponding normal tissues in 54 of 82 patients (66%). Tumor shows increased maspin expression compared with normal tissue in 81.1% of stage IV patients and 83.3% of N3 patients. The frequency of maspin induction was associated with the stage of gastric cancer (p = 0.01) and lymph node metastasis (p = 0.03). There was no significant association between maspin induction and Helicobacter pylori infection. CONCLUSIONS: Our data suggest that maspin may have an important role in the progression and metastasis of gastric adenocarcinoma.     

Expression of maspin in colon cancers: its relationship with p53 expression and microvessel density

We studied the expression of maspin in colonic adenocarcinoma compared with adenoma and metastatic adenocarcinoma as well as the relationship with its possible regulator, p53. The colonic specimens consisted of 24 adenomas, 49 adenocarcinomas, and 17 metastatic adenocarcinomas. Immunohistochemical staining of paraffin sections was done with microwave-based antigen retrieval methods. The Ki-67 index and the microvessel density were counted using an image analysis system. Maspin expression was positive in 75.5% of adenocarcinomas and 91.7% of adenomas. Only 47.1% of the nodal metastasis showed positive maspin expression. In colonic adenocarcinomas, p53 expression was positive in 44.7% of the maspin-positive groups compared with 100% of the maspin-negative groups (P < 0.005). Colonic adenocarcinomas with the positive maspin expression groups showed less intense microvessel density (181.1 ± 54.2) than those of the negative maspin expression groups (256.1 ± 75.4, P < 0.001). In conclusion, we demonstrated maspin expression in colon cancer with a sequential decreased expression rate from adenoma to metastatic carcinomas, which signifies the tumor suppressive function of maspin, and an inverse correlation with p53 and microvesel density, which indicates the regulatory effect of p53 on maspin and anti-angiogenesis effect of maspin.     

YB-1和P53蛋白在结直肠肿瘤中的表达及意义

目的:探讨YB-1和P53蛋白在结直肠肿瘤不同发展阶段表达水平的差异及其与结直肠癌临床病理特征的关系.方法:采用免疫组织化学方法检测结直肠20例正常组织、30例低级别上皮内瘤变组织、30例高级别上皮内瘤变组织和50例癌组织中YB-1和P53蛋白的表达.结果:YB-1蛋白在结直肠正常组织(NCM)、低级别上皮内瘤变组织(LGIN)、高级别上皮内瘤变组织(HGIN)和癌组织(CRC)中的强阳性率分别为0%、76.7%、80.0%、80.0%,低级别、高级别上皮内瘤变组织和癌组织中的强阳性表达率均与正常组织比较差异有统计学意义(P<0.05),且在癌组织中其强阳性表达与淋巴结转移和TNM分期有关(P<0.05);P53蛋白在结直肠正常组织、低级别上皮内瘤变组织、高级别上皮内瘤变组织、癌组织中表达分别为0%、6.7%、40.0%、60.0%,高级别上皮内瘤变组织和癌组织中其表达率均与正常组织和低级别上皮内瘤变组织比较差异有统计学意义(P<0.05),其在癌组织中的表达与分化程度、淋巴结转移和TNM分期有关(P<0.05).在癌组织中YB-1和P53的表达呈正相关性(r=0.306,P<0.05).结论:YB-1和P53蛋白在结直肠癌的发生发展、转移中起重要作用,YB-1和P53蛋白的联合检测可能为判断结直肠癌恶性程度和转移提供重要参考.     

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.     

c-erbB-2 、bcl-2和p53在结直肠肿瘤中的表达及其临床意义

背景：c-erbB-2、bcl-2和突变型p53在结直肠腺瘤癌变过程中相互调节并发挥重要作用。目的：探讨结直肠肿瘤中c-erbB-2、bcl-2和D53蛋白的表达及其临床意义。方法：取42例结直肠腺癌、10例腺瘤和10例正常结直肠黏膜组织，以免疫组化方法检测其中c-erbB-2、bcl-2和p53蛋白的表达，分析其表达与腺癌临床病理特征的关系。结果：c-erbB-2、bcl-2和p53蛋白在腺癌、腺瘤和正常黏膜组织中的表达差异均有统计学意义（P〈0．05），bcl-2蛋白在腺癌组织中的表达低于腺瘤组织，c-erbB-2和p53蛋白在腺癌组织中的表达高于腺瘤和正常黏膜组织。c-erbB-2蛋白的表达随腺癌分化程度的降低而增高，bcl-2蛋白的表达随腺癌分化程度的降低而降低：c-erbB-2和p53蛋白的表达与淋巴结转移和Dukes分期呈正相关。腺癌组织中bcl-2与p53蛋白的表达呈负相关（rs=-0．301，P〈0．05）。结论：c-erbB-2与结直肠癌的进展、分化和转移相关。腺癌组织中p53高表达和bcl-2相对低表达提示两者可能参与了结直肠癌的发生、发展过程，bcl-2过表达可能在结直肠癌发生的早期起作用。     

Expression of two CD44 variant proteins (v3 and v6 ) in human colorectalcarcinoma and its relevance for prognosis

AIM To evaluate the expression of CD44v3 and v6 protein in colorectal carcinoma and its prognosticsignificance.METHODS One hundred and twenty-one cases of formalin-fixed paraffin-embedded colorectal carcinomaspecimens were retrospectively analyzed using EnvisionTM immunohistochemical method with the monoclonalantibody CD44v3 and v6. The median follow-up time was 67.77 months and the prognostic value of theCD44v3 and CD44v6 was assessed using univariate and multivariate survival analysis.RESULTS The positive rates of CD44v3 and v6 protein were 60.3% and 57.9%, respectively. There wassignificant correlation between CD44v3 immunoreactivity and tumor location, lymph node metastasis, distantmetastasis and Duke's stage (P< 0.05, Spearman correlation test). Significant correlation between CD44v6immunoreactivity and patients' gender, lymph node metastasis, distant metastasis, Duke's stage was alsonoticed (P < 0.05, Spearman correlation test). The 5-year survival rates were 81.25% and 60.27% inCD44v3 negative and positive cases, respectively. As CD44v6, the 5-year survival rates were 80.39% and60.00% in CD44v6 negative and positive cases, respectively; these differences between the two groups ofpatients were significant (P<0.05, Log-rank test). In multivariate analysis using the Cox regression model,CD44v3 expression emerges as an independent prognostic indicator.CONCLUSION CD44v3 and v6 might play some important roles in metastasis of colorectal carcinoma, andCD44v3 expression might be a new useful independent prognostic marker of colorectal carcinoma.