胆囊腺瘤和腺癌中Survivin与p53的定位表达及病理诊断意义

目的：观察胆囊腺瘤和胆囊腺癌细胞中Survivin与p53蛋白定位表达和形态特征,研究其在病理诊断及鉴别诊断中的意义。方法：采用免疫组化方法（SP法）检测25例胆囊腺瘤和53例胆囊腺癌细胞中Sur-vivin与p53蛋白的表达。结果：25例胆囊腺瘤,23例Survivin蛋白细胞浆内表达,阳性率92%;其中21例核上表达,包括＂核上核样＂表达17例、＂核上泥沙样＂表达4例;细胞浆弥漫表达2例;p53蛋白在胆囊腺瘤组织中无表达。53例胆囊腺癌,Survivin蛋白细胞浆弥漫表达,阳性率75.47%;p53蛋白细胞核内表达,核内表达率77.36%。Survivin在胆囊腺瘤和胆囊腺癌中的表达阳性率虽无显著性差异,但表达部位和形态特征显著不同。结论：Survivin在胆囊腺瘤中的＂核上核样＂和＂核上泥沙样＂表达,特异性强,有望成为胆囊腺瘤的诊断性抗体;其与p53在胆囊腺癌组织中核阳性表达、胆囊腺瘤组织中无表达这个结果相结合,构成两者在分子形态学表达的差异性,可作为胆囊腺瘤和胆囊腺癌病理鉴别诊断中的一种分子学方法,结合HE切片,基本可解决胆囊腺瘤与胆囊腺癌的病理诊断与鉴别诊断问题。     

磷酸酶基因、核因子-KB p65、Survivin蛋白在子宫内膜样腺癌中的表达及其临床意义

目的 探讨磷酸酶基因(PTEN)、核因子(NF-KB p65)及凋亡抑制蛋白Survivin基因在子官内膜样腺癌中的表达及其在子宫内膜样腺癌的发生、发展中的作用.方法 采用SP免疫组织化学法榆测63例子宫内膜样腺癌、20例正常增生期子宫内膜组织中PTEN、NF-KB p65及Survivin蛋白的表达.结果 子宫内膜样腺癌与正常增生期子宫内膜组织中PTEN、NF-KB p65及Survivin蛋白表达的阳性率差异有统计学意义(P＜0.01).PTEN表达与子宫内膜样腺癌分化程度呈正相关(P＜0.001),与淋巴结转移及TNM分期旱负相关(P＜0.005),NF-KB p65的表达与子宫内膜样腺癌分化程度旱负相关(P＜0.05),与浸润深度、淋巴结转移及TNM分期呈正相关(P＜0.05).Survivin与子宫内膜样腺癌与浸润深度、淋巴结转移及TNM分期呈正相关(P＜0.05).结论 PTEN、NF-KB p65及Survivin在子宫内膜腺癌的发生、发展中起着不同程度的作用,联合检测PTEN、NF-KB p65及Survivin对研究子宫内膜腺癌的发生、发展、早期诊断及预后评估有一定的参考价值.     

顺铂、得力生对胰腺癌细胞株生长和凋亡的作用

目的:体外研究胰腺癌细胞株p1,p2,p3,p4,p7的Survivin、Bc l-2和p53蛋白的表达情况,顺铂、中药得力生对胰腺癌细胞株的细胞增殖和凋亡的作用,研究细胞毒性药物与中药对胰腺癌细胞的联合作用,以及相关蛋白表达对上述作用的影响。方法:免疫组化检测上述蛋白在细胞中的表达;MTT方法检测细胞的增殖;TUNEL原位检测细胞的凋亡。结果:5种细胞株中均有不同程度Survivin和p53蛋白的表达,均无Bc l-2的表达。Survivin在p1、p3表达最强,在p2表达最弱;p3主要表达在细胞浆,其余4种细胞均表达在细胞核及细胞浆;p53在p2和p4细胞中表达率最高,为60%,但是在p2细胞中表达较弱。顺铂、中药得力生对胰腺癌细胞株的细胞增殖均具有抑制作用,且有协同趋势;Survivin和p53的表达程度与顺铂对胰腺癌细胞增殖的作用呈一定的反向关系;顺铂和中药得力生诱导下均检测到凋亡细胞。结论:Survivin和p53的表达可能调节胰腺癌细胞对顺铂的药物敏感性;中西医结合治疗胰腺癌可能具有很好的应用前景。     

磷酸酶基因、核因子-κBp65、Survivin蛋白在子宫内膜样腺癌中的表达及其临床意义

目的探讨磷酸酶基因（PTEN）、核因子（NF-κB p65）及凋亡抑制蛋白Survivin基因在子宫内膜样腺癌中的表达及其在子宫内膜样腺癌的发生、发展中的作用。方法采用SP免疫组织化学法检测63例子宫内膜样腺癌、20例正常增生期子宫内膜组织中PTEN、NF-κB p65及Survivin蛋白的表达。结果子宫内膜样腺癌与正常增生期子宫内膜组织中PTEN、NF-κB p65及Survivin蛋白表达的阳性率差异有统计学意义（P〈0．01）。PTEN表达与子宫内膜样腺癌分化程度呈正相关（P〈0．001），与淋巴结转移及TNM分期呈负相关（P〈0．005），NF-κB p65的表达与子宫内膜样腺癌分化程度呈负相关（P〈0．05），与浸润深度、淋巴结转移及TNM分期呈正相关（P〈0．05）。Survivin与子宫内膜样腺癌与浸润深度、淋巴结转移及TNM分期呈正相关（P〈0．05）。结论PTEN、NF-κB p65及Survivin在子宫内膜腺癌的发生、发展中起着不同程度的作用，联合检测PTEN、NF-κB p65及Survivin对研究子宫内膜腺癌的发生、发展、早期诊断及预后评估有一定的参考价值。     

凋亡抑制蛋白Survivin在胃癌中的表达及其与bcl-2、p53蛋白相关性研究

目的：研究凋亡抑制蛋白Survivin、bcl-2、p53在胃癌组织中的表达及其与临床病理特征之间的关系，并探讨Survivin与bcl-2、p53蛋白表达的相关性。方法：采用链霉菌抗生物素蛋白-过氧化酶连接（S-P）免疫组化方法，检测Survivin、bcl-2、p53蛋白在正常胃粘膜组织及胃癌组织中的表达。结果：Survivin蛋白在正常胃粘膜组织中无表达，而在58例胃癌中41例（70．7％）表达阳性，差异有统计学意义（P〈0．01）；Survivin蛋白表达与胃癌组织病理分化程度、淋巴结转移、TNM分期相关，而与浸润程度不相关；胃癌bcl-2蛋白表达的阳性与阴性中，Survivin蛋白表达阳性率分别为81．0％（34／42）和43．8％（7／16），两者比较差异显著（P〈0．01）；p53蛋白表达的阳性和阴性中，Survivin蛋白表达阳性率分别为58．1％（18／31）和22．2％（6／27），两者比较亦有显著性差异（P〈0．05），Survivin蛋白的表达与胃癌组织中的bcl-2蛋白及p53蛋白表达密切相关。结论：Survivin蛋白异常表达可引起细胞凋亡抑制，在胃癌的发生中起一定作用，其过度表达提示胃粘膜细胞增生极度活跃；Sur-vivin蛋白表达与胃癌中bcl-2蛋白及p53蛋白的异常表达密切相关。     

Survivin和P53蛋白表达与膀胱移行细胞癌复发的关系

【摘要】 背景与目的： 分析膀胱移行细胞癌肿瘤组织中Survivin和P53蛋白的表达情况,并探讨它们与肿瘤复发的关系。 材料与方法： 应用免疫组织化学方法检测75例膀胱移行细胞癌石蜡包埋肿瘤组织中Survivin和P53蛋白的表达。并按照患者临床病理级别分层,使用Mantel-Haenszel等统计学方法分析上述两种蛋白的表达与膀胱癌复发的相对危险度及显著性水平。结果： 膀胱癌组织Survivin蛋白在胞浆、胞核检出率和P53蛋白的阳性检出率分别为76.0％、30.7％和53.33％;Survivin(胞浆)与P53并联使用阳性检出率为84.0％。以Survivin蛋白的胞浆、胞核的表达和P53蛋白表达、以及二者并联使用预测膀胱癌复发的灵敏度分别为87.50％、37.50％、71.88％和96.88％;特异度分别为32.56％,74.42％,61.90％和25.58％。使用四格表检验,Survivin蛋白胞浆检出：OR=3.38, 95％CI(0.99～11.52),P=0.044;P53：OR=3.91,P=0.005;Survivin和P53并联：OR=10.66,P=0.0087。按照病理分级分层,P53：OR=3.41, P=0.016;P53和Survivin蛋白联合应用：OR=8.86,P=0.022。 结论： 肿瘤组织中P53蛋白的过度表达提示膀胱移行细胞癌复发风险较高,但是仍需要和其他生物学指标联合应用。     

增殖细胞核抗原与p53蛋白在胶质瘤中的表达意义

本文采用PCNA和p53蛋白对45例胶质瘤进行联合探讨，发现两种核内蛋白均随肿瘤病理级别的升高而标记阳性升高。Ⅰ级组，未复发组的阳性率与Ⅱ级组、Ⅲ～Ⅳ级组、复发组相比较有显著差异（p＜0.01）．这提示肿瘤分级与病人的预后有关。本实验还证实胶质瘤的PCNA和p53蛋白易在细胞浆内表达，说明胶质瘤核与胞浆间有一定物质交换，提示可作为阳性判断．     

血管紧张素Ⅱ1型受体在肺鳞癌、腺癌中的表达及与Survivin、p53相关性研究

目的:探讨在肺鳞癌、腺癌组织中血管紧张素Ⅱ1型受体(AngiotensinⅡtype-1 receptor,AT1R)的表达及临床意义,并探讨AT1R表达及与Survivin、p53之间的相关性。方法:采用免疫组织化学方法(SP法)检测72例肺鳞癌、腺癌组织和12例癌旁正常组织中AT1R、Survivin、p53的表达。结果:AT1R在肺鳞癌、腺癌组织中的阳性表达率为48.6%,在正常组织中未检出阳性结果。AT1R阳性表达率与淋巴结转移及TNM分期呈正相关(P<0.05),与组织学类型、病理分级及是否吸烟无相关性(P>0.05)。AT1R阳性表达患者p53蛋白、Survivin阳性表达率分别为71.4%和74.3%,AT1R不表达患者p53蛋白及Survivin阳性表达率分别为29.7%和40.5%。AT1R表达与Survivin、p53蛋白表达呈正相关(P<0.01)。结论:AT1R参与了肺鳞癌、腺癌的恶性增殖和侵袭,其表达能为肺癌诊断、治疗、判断预后提供新的依据。     

大肠肿瘤组织中人乳头状瘤病毒感染与P53基因表达的研究

目的探讨HPV16和HPV18感染及P53基因异常表达与大肠肿瘤发生间的关系。方法采用地高辛标记的HPV16和HPV18DNA深外分别在40例大肠癌和30例大肠腺瘤组织石蜡切片上进行原位杂交探测HPVDNA。同时,采用SABC法检测大肠癌和大肠腺瘤的P53表达水平。结果受检大肠腺瘤组织HPVDNA阳性8例（27％）,其中HPV16DNA5例,HPV18DNA3例,主要见于管状绒毛状腺癌和绒毛状腺瘤;大肠腺癌组织中HPVDNA阳性19例（4％）,其中HPV16DNA14例,HPV18DNA5例。HPVDNA主要见于肿瘤细胞核中,少部分见于胞浆中。大肠癌组织中HPV16．18DNA检出阳性率明显高于大肠腺癌,且腺痛中HPV16DNA阳性率明显高于其他类型腺瘤。大肠癌P53蛋白阳性率为48％;腺癌的阳性率则为16．2％。结论HPV16．18型感染并整合至宿主细胞DNA中可能导致P53基因突变与大肠腺癌发生有密切关系。     

MUC1和MUC16在胆囊癌中的表达及临床意义

目的:研究MUC1和MUC16在正常胆囊黏膜、胆囊腺瘤及胆囊癌中的表达情况,以及胆囊癌中MUC1和MUC16的表达与胆囊癌Nevin分期及组织分化程度的关系。方法 :收集因胆囊息肉行胆囊切除术病例60例、胆囊腺瘤病例60例及胆囊癌病例60例,进行MUC1和MUC16的免疫组织化学染色,结合病理图像,分析其在正常胆囊黏膜组织、胆囊腺瘤及胆囊癌中的表达情况。结果:MUC1在正常胆囊黏膜组、胆囊腺瘤组和胆囊癌组中,阳性表达率分别为6.67%、38.33%、81.67%。MUC16在正常胆囊黏膜组和胆囊腺瘤组中,无阳性表达。在胆囊癌组中,阳性表达率为36.67%。MUC1和MUC16在Nevin分期 I期组、II期组、III期及III期以上组中,阳性表达率分别为62.50%、80.00%、95.83%和18.75%、30.00%、54.17%。MUC1和MUC16在高分化组、中分化组、低分化组中阳性表达率分别为60.00%、78.95%、96.15%和13.33%、26.32%、57.69%。结论:MUC1和MUC16的阳性表达在胆囊癌的发生发展中起着重要作用,MUC1和MUC16的阳性表达促进胆囊癌的发生发展。MUC1和MUC16作为一种胆囊癌的肿瘤标志物,并且预示胆囊癌的恶性程度及浸润程度。     

Expression of the c-erb-B2 and p53 protein in gallbladder carcinomas

Gallbladder carcinoma is the most common malignancy of the biliary tract in Korea and known to be more common in East Asia and Latin America than in Europe and North America. However, their exact histopathological characteristics and carcinogenesis are not well-elucidated. A total of 71 cases of gallbladder carcinomas, two cases of gallbladder dysplasia and 20 cases of gallbladder adenoma were immunohistochemically studied to evaluate the expression of c-erb-B2 and p53 proteins in the light of their relationship with various prognostic factors. Thirty-three gallbladder carcinomas (46.5%) showed positive staining for c-erb-B2, but none of the dysplasia and adenoma were positive (p<0.05). c-erb-B2 was stained in the cell membrane of the cancer cells. Adjacent normal mucosa was negative for c-erb-B2 staining. Forty-eight gallbladder carcinomas (67.6%) showed positive staining in the nucleus for p53 protein. None of the cases with dysplasia, adenoma, and normal mucosa stained positive for p53 protein. There was no significant correlation between c-erb-B2 and p53 expression and age, gender, histological tumor grade, and tumor stage. In the multivariate analysis, tumor stage approached statistical significance (p=0.05), but c-erb-B2 and p53 expression was not significant (p=0.14 and p=0.29, respectively). The mean survival periods of the c-erb-B2 positive and negative groups were 26 months and 52 months, respectively (p=0.02). However, the mean survival periods of the p53 protein positive and negative patients were 34 months and 35 months, respectively (p=0.45). In conclusion, our results suggest that c-erb-B2 and p53 protein expression is strongly associated with neoplastic progression in gallbladder carcinomas, and that c-erb-B2 expression identifies patients with a worse prognosis.     

大肠肿瘤组织p53、PCNA表达及其临床意义

目的　研究p5 3、PCNA(增殖细胞核抗原 )在大肠肿瘤组织中表达及其临床价值。方法　应用免疫组化技术 (S -P法 )检测 17例大肠腺瘤 ,7例腺瘤癌变 ,48例大肠癌组织表达。结果　大肠腺瘤p5 3阳性率为 2 9 4% ,腺瘤癌变为 71 4% ,大肠癌p5 3阳性率为5 6 3 % ,PCNA强阳性 ( ++)表达与p5 3阳性表达呈平行关系。结论　p5 3、PCNA过度表达代表腺癌细胞由良性向恶性转化区域 ,并与大肠癌的淋巴结转移和生存期相关。     

P53, COX-2, iNOS protein expression changes and their relationship with anti-oxidant enzymes in surgically and multi-modality treated esophageal carcinoma patients

Esophageal carcinoma has a high incidence in India but its etiology remains unknown. In the present study the correlation between apoptosis regulatory proteins and anti-oxidant enzymes in 40 esophageal carcinoma patients was examined. Patients in one group were operated by transhiatal esophagectomy and in the second group were administered cisplatin (30 mg/m2/day) and 5-fluorouracil (5-FU) (750 mg/m2/day) daily for three days followed by surgery after four weeks of neo-adjuvant therapy (NAT). Complete pathological response was achieved in 15% of patients. Results obtained by Western blot analysis showed over-expressed p53 and COX-2 protein levels in the tumor tissues as compared to the adjoining tissue and its paired normal mucosa in both groups of patients. Immunohistochemical studies showed heterogenous p53 staining pattern with sections showing both nuclear and cytoplasmic staining with 36.8% mild, 10.5% moderate and 52.6% intense p53 immunoreactivity. Both COX-2 and iNOS immunostaining revealed 25% negative and 75% mild to strongly positive immunoreactivity. Correlation studies demonstrated a positive relationship between p53 and COX-2 (P=0.030; r = +0.70) in surgically treated patients. The association of COX-2 and p53 with various anti-oxidant enzymes showed a significantly positive correlation between COX-2 expression and catalase activity and an inverse correlation between p53 expression and superoxide dismutase and catalase activity in the tumor tissue of patients given NAT. In addition, we observed a negative trend between p53 expression levels and GPx enzyme levels in both the adjoining and tumor tissue of patients having undergone surgery as main mode of treatment.     

p53和VEGF蛋白表达与胆囊癌的关系

目的探讨抑癌基因p53和血管内皮生长因子(vascular endothelial growth factor,VEGF)与胆囊癌的关系。方法采用免疫组化方法分别检测50例胆囊癌、35例胆囊腺瘤和26例慢性胆囊炎组织中p53和VEGF蛋白表达。结果胆囊癌组织中p53和VEGF的阳性表达率分别为64.0%和72.0%,明显高于胆囊腺瘤的17.1%和22.9%及慢性胆囊炎的19.2%和23.1%,χ2=4.25,P=0.006,根据Nevin分期,胆囊癌S1、S2、S3期的p53阳性表达率为63.2%,明显高于S4、S5期的35.5%,χ2=7.29,P=0.009,而VEGF在胆囊癌S4、S5期的阳性表达率为87.1%,明显高于S1、S2、S3期的47.4%,χ2=4.29,P=0.007,胆囊癌中p53和VEGF的阳性表达明显相关,r=0.87,P=0.009。它们与胆囊癌病理分级均未发现明显相关性。结论p53和VEGF的过度表达可能对胆囊癌的发生、发展及预后判断有一定作用。     

Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis

BACKGROUND: To identify the role of survivin, a novel inhibitor of apoptosis (IAP) in colorectal tumorigenesis, the authors investigated tissue expression of survivin in human colorectal tumors including 43 hyperplastic polyps, 171 adenomas with low dysplasia, 42 adenomas with high dysplasia, and 60 carcinomas in adenoma, and examined whether the expression of survivin correlated with tumor cell apoptosis, proliferation, and angiogenesis, which is known to initiate the imbalance between cell proliferation and apoptosis. METHODS: Immunohistochemical staining for the paraffin sections by using the monoclonal antibodies, survivin, p53, bcl-2, Ki-67, and CD34, was performed by the standard avidin-biotin-peroxidase technique. The apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method, using an Apop Tag in situ detection kit. RESULTS: The immunoreactivity of survivin significantly increased in the transition from adenoma with low dysplasia to high dysplasia/carcinoma (P < 0.001). Similar changes in protein expression were observed for p53 but not for bcl-2, which was expressed throughout the colorectal tumorigenesis. This transition was associated with a significant decrease in the apoptotic index (AI) and significant increases in the Ki-67 labeling index (LI) and microvessel density (MVD; P < 0.001 for both). The expression of survivin inversely correlated with AI and was positively correlated with Ki-67 LI and MVD (P < 0.001 for both). CONCLUSIONS: These results suggest that, like p53, survivin plays an important role in transition from adenoma with low dysplasia to high dysplasia during human colorectal tumorigenesis.     

结直肠癌组织中Survivin表达的临床病理学意义

目的 :研究凋亡抑制蛋白Survivin在结直肠癌组织中的表达及其临床病理学意义。方法 :采用SP法检测 10 6例结直肠癌组织中Sur vivin的表达 ,分析Survivin表达与各临床病理因素的关系 ;应用Kaplan Meier法分析Survivin表达对结直肠癌生存率的影响。结果 :Survivin在结直肠癌组织中的表达率为 64 2 % ( 68/10 6) ,癌旁形态学正常的结直肠黏膜未见Survivin表达 ;Survivin在中、高分化结直肠癌表达阳性率 72 4% ( 63 /87) ,明显高于低分化结直肠癌( 2 6 3 % ,5 /19) ,P <0 0 5。Survivin表达与患者性别、肿瘤位置、浸润深度、淋巴结转移、远处转移以及Duke’s分期差异无统计学意义 ,P >0 0 5。Sur vivin阳性表达的结直肠癌患者 5年生存率为 42 6% ( 2 9/68) ,Survivin阴性表达患者为 68 4% ( 2 6/3 8) ,差异有统计学意义 ,P <0 0 5。结论 :凋亡抑制蛋白Survivin在结直肠癌组织中存在高表达 ,与结直肠癌预后有关 ,可作为判断结直肠癌预后的辅助指标。     

Diagnostic utility of phosphatase and tensin homolog, beta-catenin, and p53 for endometrial carcinoma by thin-layer endometrial preparations

BACKGROUND: For the current report, the authors examined the characteristic features of morphology and molecular biology of phosphatase and tensin homolog (PTEN), beta-catenin, and p53 immunocytochemistry in endometrial carcinoma by using thin-layer cytologic preparations. METHODS: During a 6-month period, 120 endometrial samples were collected directly by using the Uterobrush, and thin-layer specimens were prepared. Immunocytochemical expression levels of PTEN, beta-catenin, and p53 were investigated by using 40 specimens of endometrial carcinoma (EC), and 30 specimens each of proliferative endometrium, secretory endometrium, and atrophic endometrium. RESULTS: For PTEN immunoreactivity, the a cutoff value of 50% PTEN expression appeared to be useful for the correct diagnosis of EC in endometrial cytology. For beta-catenin immunoreactivity, an increase in cytoplasmic and nuclear beta-catenin expression and a loss of beta-catenin expression appeared to be useful for the correct diagnosis of EC in endometrial cytology and may aid in the stratification of EC into low grade and high grade EC. For p53 immunoreactivity, the application of a cutoff score >or=4 for nuclear p53 expression appeared to be useful for the diagnosis of high-grade EC in endometrial cytology. CONCLUSIONS: Immunocytochemical findings from a combination of PTEN, beta-catenin, and p53, in addition to cytomorphologic features, appeared to be useful for the more accurate diagnosis of EC in endometrial cytology.