Expression of Survivin, CDK4, Ki-67 and Clinical Significance in Pediatric Acute Leukemia

The expression of Survivin, CDK4 and Ki-67 and the clinical significance in pediatric acute leukemia (AL) were investigated. The expression of Survivin, CDK4 and Ki-67 proteins was detected by using immunohistochemical assay in 37 children with AL and 10 children with normal bone marrow as controls. The positive expression rate of Survivin, CDK4 and Ki-67 was 45.9 %, 56.8 %, and 40.5 % respectively in 37 AL children, which was significantly higher than in control group accordingly (P<0.05). The expression of Survivin was positively correlated with CDK4 (P=0.007) and Ki-67 (P=0.008). In conclusion, all Survivin, CDK4 and Ki-67 proteins are over-expressed in pediatric AL and involved in the modulation of apoptosis and proliferation in pediatric AL.     

Expression of p57kip2 and cyclinE proteins in human pancreatic cancer

Objective To investigate the effects of p57kip2 and cyclinE proteins on the genesis and progression of human pancreatic cancer. Methods The expression of p57kip2 and cyclinE proteins in tumor tissues and adjacent tissues of pancreatic cancer in 32 patients was detected by SP immunohistochemical technique. Results The p57kip2 protein positive-expression rate in tumor tissues of pancreatic cancer was 46.9%, which was lower than that in adjacent pancreatic tissue (P&lt;0.05). The p57kip2 protein positive-expression correlated significantly with tumor cell differentiation (P&lt;0.05) and did not correlate significantly with lymph node metastasis (P&gt;0.05). The cyclinE positive-expression rate in tumor tissues was 68.8%, which was higher than that in adjacent pancreatic tissues (P&lt;0.05). The cyclinE positive-expression also correlated significantly with tumor cell differentiation and lymph node metastasis (P&lt;0.05). The cyclinE protein positive-expression rate in the tumor tissues of the p57kip2 protein positive-expression group was lower than that in the p57kip2 protein negative-expression group, and there were no significant correlation between the two groups (r= -0.112, P＞0.05).Conclusion Decreased expression of the p57kip2 protein and/or over-expression of the cyclinE protein may play an important role in the genesis and progression of human pancreatic cancer.     

Expression of Beclin1 in non small cell lung cancer and its clinical significance

Objective:To investigate the expression of autophagy related gene;Beclin1 in human non-small cell lung cancer(NSCLC)tissues.Methods:Protein expression of Beclin1 was determined by immunofluorescence staining and Western Blot,mRNA expression was analyzed by RT-PCR.Results:Immunofluorescence staining revealed that the level of Beclin1 expression in lung cancer was significantly lower than that in adjacent noncancerous tissues and normal tissues(expression rate 8.3%,P=0.000).The Beclin1 mRNA expression in lung cancer,adjacent noncancerous tissues and normal tissues was 1.372(±0.475)1.721(±0.521)and 1.553(±0.554)when F = 15.0,P < 0.01.Beclin1 protein expression in lung cancer,adjacent noncancerous tissues and normal tissues was 3.453(±0.852)5.423(±1.351)and 6.878(±0.997)F = 11.2,P < 0.01.Conclusion:The protein and mRNA expression of Beclin1 in lung cancer was much lower than those in and around cancer tissues and normal tissues,those differences having statistical significance.However in adjacent noncancerous tissues and normal tissues,the expression showed no difference.     

Expression and Prognostic Significance of Livin in the Progression of Bladder Cancer

It has been suggested that progression of bladder transitional cell cancer (BTCC) may be regulated at the molecular level by a typical pattern of expression of genes involved in apoptosis. Re-cently Livin, belonging to the inhibitors of apoptosis (IAP) family, has been found to be expressed in most solid tumors, where its expression is suggested to have clinical significance. In order to explore the significance of Livin expression in the development of BTCC, immunohistochemistry and RT-QPCR were used to detect the expression of Livin mRNA in tumor tissues and adjacent normal tissues of 30 cases of BTCC. The results showed that the positive rate of Livin expression in adjacent normal tissues and tumor tissues was 0 and 60% (18/30) respectively. The -△△CT value of Livin in BTCC tissues was 8.0454 (7.4264-8.6644) times of that in adjacent normal tissues. The expression of Livin mRNA had no correlation with tumor pathological grades and clinical stages. It was sug-gested that there was weak expression of Livin mRNA in adjacent normal tissues, but strong in tumor tissues.     

P53 Gene Mutation and Expression of MDM2, P53, P16 Protein and their Relationship in Human Glioma

To investigate the effect of P53 protein accumulation and p53 gene mutation in the pathogenesis of glioma and to study the role of MDM2, P53 and P16 protein in glioma formation and progression and their relationship with each other, LSAB immunohistochemical staining method and non-isotopic PCR-SSCP techniques were used to detect the expression of MDM2, P53 and P16 protein and p53 gene mutation in 48 cases of gliomas. The results showed that the positive expression rate of MDM2, P53 and the negative rate of P16 was 22.9 %, 41.7 % and 60.4 %, respectively. The latter two in high grade （grade Ⅲ , Ⅳ） gliomas had a significantly higher rate than in the low grade （grade Ⅱ ） gliomas. Moreover, the co-expression of MDM2 and P53 protein was confirmed in only 1 of 48 cases. No significant difference was found in the rate of the expression of MDM2 between high grade and low grade gliomas （P〉0.1） . PCR-SSCP results showed that mutation of 5 --8 exons of p53 gene was detected in 17 out of 48 cases （35.42 %） . Mutation was detected in 16 of 20 cases of positive p53 expression, and another one was detected in 28 cases of negative expression cases. The correlation between p53 mutation and p53 immunopositivity was observed in 89.6 % of the cases. P53 gene mutation and the level of MDM2, P53 and PI6 protein were not related to age, gender of the patients, tumor location and size. It is concluded that the mutation of p53 and deletion of p16 might play important roles in the tumorigenesis of gliomas and it was significantly associated with the grade of tumor differentiation. P53 protein accumulation can indirectly reflect p53 mutation. MDM2 amplification and overexpression might be an early event in the growth of human gliomas.     

Expressions of Nucleoside Diphosphate Kinase （nm23） in Tumor Tissues are Related with Metastasis and Length of Survival of Patients with Hepatocellular Carcinoma

Objective To evaluate the relationship of expressions of nucleoside diphosphate kinase （nm23） and proliferating cell nuclear antigen （PCNA）, as well as apoptosis, with the prognosis of HCC patients by analyzing their pathological and clinical data. Methods The expressions of nm23 and PCNA were analyzed by immunohistochemistry and the apoptotic phenomena were detected by TUNEL technique in the liver samples from 43 HCC tissues, 39 para-neoplastic tissues, and 10 normal tissues. The mean apoptosis index （AI） and proliferative index （PI） in individual sample were calculated. Results As shown by the detection, 32.6% of carcinomas had negative nm23 signal in tumor tissues, whereas all para-neoplastic and normal tissues had positive nm23. The AI in nm23 positive HCC was significantly higher than that in nm23 negative one, with statistical difference （P0.05）. Furthermore, the expressions of nm23, and the values of AI and PI were contrastively analyzed with some main pathological and clinical data of HCC. It revealed that HCC with extrahepatic metastasis showed remarkable correlation with the negative nm23 （P=0.013） and higher PI values of HCC （P=0.015）. The disease-free survival in HCC patients with negative nm23 expression was significantly poorer than that in patients with positive nm23 expression. Conclusion These data suggest that expressions of nm23 protein in tumor tissues are correlated with occurrences of metastasis and length of survival of the HCC patients, which may be an indicator for their prognosis.     

Correlation and expression of COX-2 and P53 protein in basal cell carcinoma of eyelid

The correlation between the expression of COX-2 and p53 protein in basal cell carcinoma （BCC） of eyelid and apoptosis was investigated. Specimens of BCC were collected from 40 cases （aged 28-68 y） at the Department of Pathology, Renmin Hospital of Wuhan University, and Department of Pathology, Zhongnan Hospital of Wuhan University during from 1999 to 2006. Five specimens of paracancerous tissues served as control group. Immunohistochemical staining was performed to detect the expression of COX-2 and p53 in the tissues. The average absorbance （A） and the average positive area rate of COX-2 and p53 protein were measured by image analysis. The positive area rate of COX-2 and p53 protein was analyzed by linear correlation analysis. It was found that COX-2 and p53 proteins were highly expressed in BCC of eyelid, and weakly expressed in paracancerous tissues. Image analysis revealed that the expression of COX-2 and p53 proteins in BCC of eyelid was sig- nificantly higher than that in paracancerous tissues （P〈0.01）. Spearman rank correlation analysis demonstrated a positive correlation between the expression of COX-2 and p53 （r=0.113, P=0.421）. It was concluded that COX-2 can increase the expression of p53 protein, therefore suppressing apoptosis.     

Expression and significance of P53 protein and MDM-2 protein in human gliomas

Background  P53 is one of the most studied tumor suppressors in the cancer research, and over 50% of human tumors carry P53 mutations. MDM-2 is amplified and/or overexpressed in a variety of human tumors of diverse tissue origin. The aim of this study was to examine the expression of P53 protein and MDM-2 protein in gliomas, and to investigate the relationship between the expression of the two proteins and the histopathological grades of glioma. The relationship between MDM-2 protein expression and P53 protein expression was also analyzed.

Methods  The expression of P53 protein and MDM-2 protein was immunohistochemically detected using monoclonal antibodies in 242 paraffin embedded tissues, including 30 normal brain tissues from patients with craniocerebral injury and 212 tissues from patients with primary glioma (grade I–II group: 5 cases of grade I, 119 cases of grade II; and grade III–IV group: 53 cases of grade III, and 35 cases of grade IV).

Results  The P53 positive rate was significantly higher in the glioma groups than in the control group (P <0.0001). The P53 positive rate was significantly higher in glioma tissues of grade III–IV than in glioma tissues of grade I–II group (P=0.001). The MDM-2 positive rate was significantly higher in glioma groups than in the control group (P <0.0001). There was no significant difference in the MDM-2 positive rate between the two glioma groups (P=0.936). The expression of P53 protein was not related to expression of MDM-2 protein (P=0.069)

Conclusions  Overexpression of P53 protein might be related to the occurrence and progression of glioma. Overexpression of MDM-2 protein may play an important role in glioma tumorigenesis, but may not be involved in glioma progression. The overexpression of MDM-2 protein was an early event in malignant transformation of glioma. MDM-2 may be a key player in glioma in its own right.

     

肝癌组织survivin的表达与凋亡,增殖和p53的关系

目的：研究肝癌survivin的表达与细胞增殖、凋亡以及053表达的关系．方法：应用免疫组化法检测原发性肝癌组织42例、癌旁肝硬化组织34例、正常肝组织10例中survivin,p53,增殖细胞核抗原（PCNA）的表达．应用TUNEL法检测细胞凋亡．结果：在42例肝癌组织中survivin阳性30例（71．4％）,显著高于癌旁肝硬化组织（11．8％）和正常肝组织（0％,P〈0．001）．肝癌中survivin蛋白的高表达与病理分级（P=0．003）,p53蛋白水平（P=0．008）、细胞增殖凋亡比（P=0．001）及患者生存时间（P=0．002）存在显著相关性,而与年龄、性别、肿瘤大小、临床分期、门脉癌栓（局部转移）无显著相关（P〉0．05）．结论：肝癌组织survivin高表达在打破肝癌细胞的增生和凋亡之间的平衡中起着重要作用．Survivin可能抑制p53阴性肝癌细胞的凋亡,在肿瘤细胞的进一步恶性转化中发挥作用．     

肝癌组织中PTEN的表达及其与p53、细胞增殖和凋亡的关系

目的:研究肝细胞肝癌(HCC)组织中PTEN的表达与细胞增殖及凋亡的关系及其与p53的相关性,明确PTEN是否参与HCC的发生、发展. 方法:利用免疫组织化学技术检测47例经术后病理学证实的HCC组织、42例癌旁肝组织及10例健康肝组织中PTEN,p53,增殖性核抗原(PCNA)的表达;用TUNEL法检测HCC中细胞凋亡水平. 结果:10例正常肝组织、42例癌旁肝组织中PTEN全部阳性表达(100%);53%(25/47)的HCC组织PTEN蛋白表达缺失. PTEN的表达与肝癌细胞的增殖指数和凋亡指数无相关性,与肝癌的浸润转移具有相关性,与p53的表达有相关性. 结论:肿瘤抑制基因PTEN和p53有相互作用. PTEN蛋白表达缺失可能在HCC的进展过程中发挥主要作用.     

肝癌组织survivin的表达及其与HBV感染的关系

目的:研究肝癌组织中的survivin的表达与HBV感染的关系. 方法:应用免疫组化法检测原发性肝癌组织45例,癌旁肝硬化组织25例,肝硬化组织18例,肝炎组织5例,正常肝组织10例中survivin的表达,同时检测原发性肝癌中HBsAg的表达. 结果:在45例肝癌组织中survivin阳性34例(75.5%),阳性率高于癌旁肝硬化组织(44.4%),肝硬化组织(0),肝炎组织(0)和正常肝组织(0,P＜0.001). 肝癌中survivin的表达在Edmondson分级Ⅲ～Ⅳ级高于Ⅰ～Ⅱ级(P=0.014),而在年龄、性别、肿瘤大小、临床分期、是否有门脉转移方面无统计学差异(P＞0.05),survivin与HBsAg的表达呈正相关(P=0.014). 结论:肝癌组织中survivin高表达说明其在肝癌发生发展中起重要作用,同时HBV感染对于survivin表达上调有一定作用.     

鼠双微粒体-2基因和突变型p53基因表达与肝癌细胞增殖和凋亡关系的研究

目的　探讨鼠双微粒体 2 (murine double minute 2, MDM2) 基因和突变型 p53 基因表达及其与肝癌细胞增殖和凋亡的相关关系。方法　应用免疫组织化学、原位分子杂交和 TUNEL 方法检测原发性肝细胞癌组织中MDM2基因和突变型 p53基因表达与肝细胞癌组织中癌细胞增殖和凋亡情况, 并分析 MDM2 基因和 p53 基因表达与肝细胞癌组织学分级、类型、增殖和凋亡的相关关系。结果　①MDM2蛋白和mRNA 、p53蛋白和mRNA 在肝细胞癌组织中阳性表达率明显高于癌旁肝组织和正常肝组织 (均P<0 .05); MDM2 mRNA阳性表达与肝细胞癌组织学分级和类型无相关关系 (均P>0 05); p53 mRNA阳性表达与肝细胞癌组织学分级具有相关关系 (P<0 .05)。②肝细胞癌组织中癌细胞增殖和凋亡的阳性率分别为 100%和 50%, 两者相比差异有极显著性意义 (P< 0 .01); MDM2mRNA 和 p53 mRNA阳性表达与肝癌细胞增殖均具有相关关系 (均P<0. 05), 但与肝癌细胞凋亡均无相关关系 (均P>0. 05)。结论　MDM2 和 p53的蛋白和mRNA在肝细胞癌组织中呈过表达状态, MDM2 基因和 p53基因过表达在肝细胞癌发生、增殖和分化中起重要作用。     

胃癌组织P53、P63蛋白表达及细胞凋亡的研究

目的：探讨P53、P63蛋白表达及细胞凋亡在胃癌发生发展中的可能机制。方法：选择57例手术切除的胃癌及胃癌旁组织,用免疫组化方法检测组织中的P53、P63蛋白表达,同时用Tunel方法检测胃癌组织中的凋亡细胞。结果：胃癌组织P53、P63蛋白表达率显著高于胃癌旁组织（P〈0.05）;低、未分化型腺癌表达率显著高于高、中分化型腺癌（P〈0.05）;有淋巴转移显著高于无转移组（P〈0.05）;P53、P63高表达的癌组织,细胞凋亡指数减少,早期胃癌低于晚期胃癌（P〈0.05）。结论：胃癌组织P53、P63蛋白高表达,可能延缓细胞凋亡;细胞凋亡机制障碍可能是胃癌增生失控的基础。     

HBx、Survivin及P53在肝细胞癌中的表达及意义

目的探讨乙型肝炎病毒X蛋白（HBx）、生存素（Survivin）及抑癌基因P53在肝细胞癌（HCC）中的表达及意义。方法采用SP免疫组化方法检测58例HCC患者中HBx、Survivin及P53蛋白的表达,并分析其与临床病理特征的关系。结果 HCC组织中HBx的表达率为46.6%（27/58）。HBx蛋白阳性的HCC组织和HBx蛋白阴性的HCC组织中Survivin、P53蛋白的阳性表达率分别为70.4%（19/27）、74.1%（20/27）和35.5%（11/31）、38.7%（12/31）,组间比较差异均有统计学意义（均P〈0.05）。HBx与Survivin、P53表达呈正相关（r=0.413 6、0.432 2,P〈0.05）。HBx染色的阳性率与AFP水平和分化程度相关;Survivin染色的阳性率与TNM分期和淋巴结转移相关;P53染色的阳性率与门静脉癌栓和肿瘤直径相关。结论在HCC的发生过程中HBx蛋白可上调Survivin及P53蛋白的表达,促进HCC的发生发展     

p57kip2在肝癌组织中的表达及其与临床病理因素、PCNA和p53的关系

目的:检测细胞周期抑制因子p57kip2在肝癌中的表达水平,探讨它与临床病理因素、增殖细胞核抗原(PCNA)、p53的关系. 方法:用免疫组织化学法检测32例肝癌组织和10例正常肝脏组织中p57kip2, PCNA和p53的表达水平. 结果:p57kip2在肝癌组织中的阳性率56.2%,显著低于正常肝脏组织(100%)(P=0.011),p57kip2的缺失表达与肝癌细胞的分化较差(P=0.007)、临床分期较晚(P=0.041)及预后较差有关(P=0.036),与年龄、AFP, 肿瘤大小及肿瘤侵犯转移无显著相关(P>0.05);PCNA在肝癌组织中阳性率为56.2%,与p57kip2的表达有关(P=0.036);p53在肝癌组织中的阳性率46.9%,与p57kip2表达在统计学上无相关性(P>0.05). 结论:肝癌组织中存在p57kip2的表达缺失、PCNA的高表达, 共同参与肝癌的发生、发展,而p57kip2和p53可能通过不同途径来诱导细胞凋亡.     

肝细胞癌中FHIT、Survivin和Caspase-3的表达及意义

目的:研究脆性组氨酸三联体蛋白(FHIT)、Survivin和Caspase-3在肝细胞癌(HCC)中的表达及其意义。方法:通过免疫组化S-P法检测75例HCC及相应癌旁组织中FHIT、Survivin和Caspase-3的表达,分析其内在联系及与HCC临床病理特征的关系。结果:FHIT在HCC和癌旁组织中的表达阳性率分别为38.7%和69.3%,Survivin为86.7%和8%,Caspase-3为29.3%和84%,差别均有统计学意义(P<0.05)。FHIT蛋白的丢失与肿瘤的分化程度相关(P<0.05),与肿瘤大小、有无包膜、是否有门静脉癌栓、甲胎蛋白和HBsAg是否阳性无明显相关性。Survivin表达阳性率与肿瘤大小有关(P<0.05),与其他临床病理特征无关。Caspase-3蛋白的表达强度与HCC的分化程度和大小呈负相关(P<0.01)。在HCC中,FHIT与Survivin、Caspase-3与Survivin的表达呈负相关,FHIT与Caspase-3的表达呈正相关(P<0.05)。结论:FHIT和Caspase-3的表达缺失或下调与Survivin的过表达可能通过凋亡抑制共同参与了肝细胞肝癌的发生和发展。     

肝细胞癌组织中Skp2的表达及与p27kip1、PCNA蛋白表达的关系

目的:探讨Skp2的表达在肝细胞癌(HCC)发生发展中的作用,及其与p27kip1(p27)和PCNA的关系。方法:收集76例HCC及癌旁组织,l0例肝血管瘤旁肝组织的临床病理档案资料,l0例HCC及癌旁肝新鲜组织,采用免疫组织化学方法及免疫印迹技术检测Skp2、p27及PCNA蛋白在这些组织中的表达。结果:免疫印迹结果显示:Skp2在HCC组织中的表达明显高于对应的癌旁肝组织。免疫组织化学结果显示HCC中Skp2的阳性率(24.08%)显著高于癌旁组织和正常肝组织(P<0.001)。Skp2的表达与肝癌组织分化程度,血清AFP值及转移有关(P<0.05)。p27在正常肝组织和癌旁组织中的表达明显高于HCC组织(P<0.001)。HCC组织中PCNA蛋白的表达明显高于癌旁和正常组织(P<0.01)。HCC组织中Skp2的表达与p27呈负相关(P<0.001);与PCNA呈正相关(P<0.01)。结论:Skp2在HCC组织中表达是上调的,可能是通过作用于细胞周期调控蛋白p27,加速了对p27泛素化依赖的蛋白降解,使其表达及代谢发生异常。导致细胞周期失控并促进细胞异常增殖,从而参与了HCC的发生和发展。     

尿路上皮癌中Survivin,p53,bcl-2的表达及意义

目的:探讨Survivin,p53,bcl-2在尿路上皮癌组织中的表达及其与肿瘤恶性程度之间的相关性.方法:用免疫组化方法检测54例尿路上皮癌组织、10例正常膀胱黏膜组织及15例对照癌旁组织中Survivin,p53,bcl-2的表达,并与肿瘤恶性度进行相关性分析.结果:Survivin,p53,bcl-2在尿路上皮癌组织中的表达阳性率分别为 70.37%,57.41%和46.30%,明显高于正常膀胱黏膜组织及对照癌旁组织.Survivin和p53的表达与肿瘤的病理分级和病理分期显著正相关(P<0.05);bcl-2的阳性表达与肿瘤病理分级和病理分期呈负相关(P<0.05).Survivin与p53的表达呈显著正相关(P<0.05);Survivin与bcl-2的表达呈显著负相关(P<0.05).结论:Survivin在尿路上皮癌组织中表达明显高于非癌组织,表明其在尿路上皮癌的发生、发展中占有重要作用;Survivin和p53的高表达提示尿路上皮癌预后不良. Survivin在尿路上皮癌中的表达与p53,bcl-2的异常表达密切相关,具有潜在的临床价值.