p53蛋白表达和肿瘤微血管生成与肝癌发展及预后的关系

目的探讨p53蛋白表达和肿瘤微血管生成与肝细胞癌(HCC)发展及预后的关系.方法采用免疫组化方法检测50例肝细胞癌组织中p53蛋白的表达,并用抗CD34抗体标记癌组织血管内皮细胞,计算肿瘤微血管密度(microvessl density,MVD).分析p53蛋白和MVD与HCC临床病理学特征之间的关系.结果 p53阳性表达为癌细胞核棕黄色着色,CD34染色定位在血管内皮细胞上,HCC的p53表达及MVD与肿瘤大小、病灶数目、病理分级、门静脉癌栓形成、包膜是否完整显著相关(P＜0.05).p53蛋白表达阳性者MVD值显著高于阴性者(P＜0.05);p53蛋白表达阳性或MVD≥148的肝癌患者术后生存时间比p53蛋白表达阴性或MVD＜148者短(P＜0.05).结论 p53与肿瘤血管生成密切相关,p53蛋白及MVD可作为肝癌预后判断的一个重要指标.     

胃癌中p27、p53蛋白及TGF—βRⅡ的关系和预后意义

目的：探讨p27、p53蛋白及TβRⅡ在胃癌中的表达关系和预后意义。方法：用免疫组化法同步检测人胃癌组织中27,p53,TβRⅡ的表达。结果：62例胃癌中p27蛋白失表达率为58．1％，高于胃癌旁组织20.0%;p53和TβRⅡ阳性率在胃癌中分别为43．5％和17．7％，而癌旁组织分别为0和50％。p27阳性组的p53,TβRⅡ阳性率（分别为65.4%,31.0%)显著高于p27阴性组（P＜0．05),p27与p53及TβRⅡ呈正相关；而p53与TβRⅡ差异无显著性（P＞0．05）。Kaplan-Meier曲线显示p27,TβRⅡ阴性组及p53阳性组患者的预后较对照组差（P＜0．05），Cox回归模型分析显示，p27与预后弱相关（P=0.0561),p53和TβRⅡ与预后密切相关（P＜0．05）。结论：p27,p53,TβRⅡ相互作用，对胃癌发生发展起重要作用；p27和TβRⅡ表达愈强,p53表达愈弱，说明预后较好，反之则差。联合检测p27,p53，TβRⅡ，可辅助胃癌诊断，估计预后，选择治疗方案。     

胃癌组织中p53基因突变及p53和mdm2蛋白表达的研究

目的：探讨mdm2和p53基因异常在胃癌发生发展中的作用以及两者相关性。方法：应用免疫组化技术检测58例胃癌组织以及相应癌旁组织中mdm2和p53蛋白的表达；PCR-SSCP银染技术检测p53基因exon5～8突变情况。结果：胃癌组p53和mdm2蛋白阳性率分别为86．21％（50／58）和29．31％（17／58），癌旁组织组p53和mdm2蛋白均为阴性，胃癌组p53和mdm2蛋白阳性率明显高于癌旁组织组，两两间差异有统计学意义，P=0．0000、P=0．0001。胃癌组织中p53和mdm2蛋白表达率与肿瘤大小、组织学类型、分化程度、淋巴结转移以及患者年龄等无显著相关性，P〉0．05。mdm2蛋白阳性表达与p53蛋白过表达呈显著正相关,X^2=11．1839，P=0．0008，r=0．4391。2例胃癌组织检测到p53基因突变，突变均位于exon5，58例相应癌旁组织均禾检测到p53基因突变。结论：mdm2和p53蛋白异常表达与胃癌发生有关，p53基因突变可能并非胃癌组织中p53蛋白异常累积的主要原因，mdm2蛋白在胃癌发生发展中的作用可能与p53蛋白密切相关。     

p53蛋白在胃癌中的表达及其与预后的关系

ｐ５３蛋白在胃癌中的表达及其与预后的关系龚志军１朱慰祺２施达仁２罗恩钊１无论在结构和功能上，ｐ５３基因都是被研究得较为清楚的一个抑癌基因，它与癌细胞生物学行为和患者预后的关系，文献报道颇多，但分歧较大，为此，本文采用免疫组织化学ＡＢＣ法检测了９７例胃...     

胃癌中p27、p53蛋白及TGF-β RⅡ的关系和预后意义

目的探讨 p27、p53 蛋白及 T β RⅡ在胃癌中的表达关系和预后意义.方法用免疫组化法同步检测人胃癌组织中 p27、p53、T β RⅡ的表达.结果62 例胃癌中 p27 蛋白失表达率为58.1%,高于胃癌旁组织20.0%;p53 和 T β RⅡ阳性率在胃癌中分别为43.5%和17.7%,而癌旁组织分别为 0 和 50%.p27 阳性组的 p53、T β RⅡ阳性率(分别为65.4%、31.0%)显著高于 p27 阴性组(P<0.05),p27与 p53 及 T β RⅡ呈正相关;而 p53 与 T β RⅡ差异无显著性(P>0.05).Kaplan-Meier 曲线显示 p27、T β RⅡ阴性组及 p53 阳性组患者的预后较对照组差(P<0.05),Cox 回归模型分析显示,p27 与预后弱相关(P=0.056 1),p53 和 T β RⅡ与预后密切相关(P<0.05).结论p27、p53、T β RⅡ相互作用,对胃癌发生发展起重要作用;p27 和 T β RⅡ表达愈强、p53 表达愈弱,说明预后较好,反之则差.联合检测 p27、p53、T β RⅡ,可辅助胃癌诊断、估计预后、选择治疗方案.     

胃癌组织中p53基因突变及p53和mdm2蛋白表达的研究

目的探讨mdm2和p53基因异常在胃癌发生发展中的作用以及两者相关性。方法应用免疫组化技术检测58例胃癌组织以及相应癌旁组织中mdm2和p53蛋白的表达;PCR-SSCP银染技术检测p53基因exon5~8突变情况。结果胃癌组p53和mdm2蛋白阳性率分别为86·21%(50/58)和29·31%(17/58),癌旁组织组p53和mdm2蛋白均为阴性,胃癌组p53和mdm2蛋白阳性率明显高于癌旁组织组,两两间差异有统计学意义,P=0·0000、P=0·0001。胃癌组织中p53和mdm2蛋白表达率与肿瘤大小、组织学类型、分化程度、淋巴结转移以及患者年龄等无显著相关性,P>0·05。mdm2蛋白阳性表达与p53蛋白过表达呈显著正相关,χ2=11·1839,P=0·0008,r=0·4391。2例胃癌组织检测到p53基因突变,突变均位于exon5,58例相应癌旁组织均未检测到p53基因突变。结论mdm2和p53蛋白异常表达与胃癌发生有关,p53基因突变可能并非胃癌组织中p53蛋白异常累积的主要原因,mdm2蛋白在胃癌发生发展中的作用可能与p53蛋白密切相关。     

p53和血管内皮生长因子表达与胃癌血管生成的关系

目的 :探讨p5 3和血管内皮生长因子表达与胃癌血管生成的关系。方法 :应用免疫组织化学方法检测 76例胃癌组织的p5 3蛋白、血管内皮生长因子 (VEGF)与微血管密度 (MVD)表达 ,分析p5 3蛋白、VEGF及MVD表达与临床病理指标之间的关系。结果 :胃癌组织p5 3蛋白与VEGF阳性表达率分别为 4 2 1% (32 76)和 38 2 % (2 9 76) ,MVD平均计数为 36 6± 17 2 ( x±s) ;p5 3、VEGF、MVD表达与肿瘤浸润深度 (P <0 0 5 ,P <0 .0 1,P <0 .0 5 )、淋巴结转移 (P <0 0 1,P <0 0 5 ,P <0 0 1)和远处转移 (P <0 0 1,P <0 0 1,P <0 0 1)密切相关 ;p5 3蛋白与VEGF表达密切相关 (χ2 =35 3916,P <0 0 1,P <0 0 1)。结论 :VEGF与MVD表达是反映胃癌生物学行为的重要标志 ,p5 3表达可能通过上调VEGF而促进胃癌血管生成     

p53和P-gp蛋白在胃癌中的表达

目的　研究胃癌组织中p5 3和P 糖蛋白表达的意义。方法　应用SP免疫组织化学的方法对 98例胃癌进行检测。结果　在 98例胃癌中 ,5 9.8%的 p5 3表达阳性 ,5 7.1%的P 糖蛋白表达阳性。p5 3和P 糖蛋白与胃癌的分化程度和生存期限有关 (P <0 .0 5 )。p5 3还与胃癌的浸润程度 ,淋巴结转移情况有关。P 糖蛋白表达阳性者 ,在 p5 3表达阳性组 ,明显高于 p5 3表达阴性组。 结论　联合检测 p5 3蛋白和P 糖蛋白对胃癌的诊断、治疗和预后有重要意义     

p53蛋白表达与胃癌生物学行为的关系

目的探讨ｐ５３蛋白表达与胃癌生物学行为的关系。方法采用免疫组织化学的链霉抗生物素蛋白－过氧化物酶（ＳＰ）法，检测５５例胃癌石蜡切片中ｐ５３蛋白的表达。结果全组阳性表达率为６０％，细胞分化越差，组织浸润程度越深，淋巴经转移数越多，则ｐ５３蛋白的表达频率和水平越高。结论ｐ５３基因蛋白表达对胃癌有较好的预后价值。     

p53 expression and prognosis in gastric carcinoma.

Abnormalities of the p53 gene have been identified in many malignancies, with reports of aberration in over half of colorectal, lung, breast and hepatocellular carcinoma cases. The normal gene acts as a recessive oncogene, while mutations change the apparent function to that of a dominant oncogene. In this investigation a 3-layered immunoperoxidase technique was applied to routinely fixed and paraffin-embedded tissue sections from 125 gastric carcinomas, using a polyclonal anti-p53 antibody (CM-I). We found that 57% of these carcinomas expressed high levels of p53 protein (positive nuclear staining). Survival analysis revealed a strong association between p53 status of the tumour and patient survival time after diagnosis (p = 0.02, Mantel-Cox Test); odds ratio of death, 2.09 (95% confidence interval 1.02 to 4.25). The 5-year survival of patients with p53-expressing tumours was 24%, compared with 56% for those non-p53-expressing tumours (the median survival times were 13 and 102 months, respectively).     

IGF-Ⅱ和HGF mRNA表达与胃癌微血管密度的关系

目的　探讨胰岛素样生长因子 Ⅱ (IGF Ⅱ )和肝细胞生长因子 (HGF)mRNA在胃癌组织中的表达及其与肿瘤微血管密度 (MVD)、侵袭、脉管侵犯、转移及预后的关系。方法　应用原位杂交和免疫组织化学方法 ,检测 10 5例胃癌组织中IGF Ⅱ和HGFmRNA及CD34的表达。结果　IGF Ⅱ和HGFmRNA在胃癌中的阳性表达率分别为 4 9.5 %和 5 7.1%。胃癌的侵袭深度、脉管侵犯、淋巴结及远处转移均与IGF Ⅱ和HGFmRNA的表达水平有关 (P均 <0 .0 5 )。乳头状腺癌MVD为 (30 .71± 14 .4 5 )个 / 0 .72mm2 ,均低于其他肿瘤类型 ;T3和T4期、脉管侵犯、有淋巴结及远处转移胃癌患者的MVD分别为 (45 .6 4± 11.6 9)、(44 .6 8± 12 .33)、(45 .6 2± 11.6 9)和 (5 1.6 9± 5 .2 1)个 / 0 .72mm2 ,分别比T1和T2期、无脉管侵犯、无淋巴结转移和无远处转移的胃癌患者高。IGF Ⅱ和HGFmRNA表达阳性患者的MVD分别为 (43.0 1± 13.5 8)和 (44 .30± 13.31)个 / 0 .72mm2 ,分别高于表达阴性的患者 [(35 .92±14 .6 2 )和 (32 .94± 13.5 4 )个 / 0 .72mm2 ];MVD分别与IGF Ⅱ和HGFmRNA的表达水平呈正相关 (rs 分别为 0 .2 2 2和 0 .399)。IGF Ⅱ和HGFmRNA表达阳性及MVD值≥ 39.5个 / 0 .72mm2 患者的平均生存时间及 5年生存率均低于表达阴性及MVD     

Overexpression of p53 associated with tumor angiogenesis, tumor cell proliferation, and prognosis in gastric carcinoma

Mutations in the p53 gene seem to be the most common genetic change in human malignancies. Recently, it was reported that p53 mutation was significantly associated with prognosis in various cancers. In this study, we investigated the correlation between p53 overexpression and prognosis of gastric carcinoma using immunohistochemical staining with an anti-p53 antibody. Although there was no significant association between p53 status and various clinicopathologic factors, prognosis of patients with p53-positive tumors was significantly worse than of those with p53-negative: tumors. Both microvessel count (MVC; the mean number of microvessels in the five areas of highest vascular density at 200x magnification) and PCNA labeling index (PCNA LI; percentage of positive cells per more than 500 tumor cells) were significantly higher in p53-positive tumors than in p53-negative tumors. In summary, it is suggested that p53 overexpression is closely associated with tumor angiogenesis, tumor cell proliferation and prognosis of gastric carcinoma.     

Loss of maspin expression is associated with development and progression of gastric carcinoma with p53 abnormality

Maspin, a serine protease inhibitor related to the serpin family, was originally identified in normal mammary epithelium. Reduced expression of maspin is related with development, invasion and metastasis of certain human cancers. In the present study, the expression of maspin was examined in gastric mucosa, adenoma and carcinoma by immunohistochemistry and RT-PCR. In non-neoplastic mucosa, maspin was expressed in cytoplasm and cell membrane of foveolar epithelia, fundic glandular cells and pyloric glandular cells. Maspin expression was lost in 71% (71/100) of gastric carcinomas, and in 19% (4/21) of adenomas, respectively. Loss of maspin expression was significantly associated with poorly differentiated histology, advanced stage and deep invasion (P<0.001). There was an inverse correlation between maspin expression and abnormal p53 accumulation. Maspin mRNA expression was lost in all of 8 gastric carcinoma cell lines that was retrieved after treatment with demethylation agent 5-aza-2'-deoxycytidine in 5 of 8 cell lines. These results suggest that loss of maspin expression partly due to DNA methylation may participate in tumor development and progression of gastric carcinoma in relation with p53 pathway. Loss of maspin expression may serve as a biological marker of high-grade malignancy.     

VEGF and bFGF expression and microvessel density of maxillary sinus squamous cell carcinoma in relation to p53 status, spontaneous apoptosis and prognosis

We have previously reported that p53 mutations, loss of bax expression or decreased spontaneous tumor apoptosis were associated with poorer prognoses in maxillary sinus squamous cell carcinoma (SCC)(Cancer 94: 1968-1980, 2002). In the present study, we analyzed tumor angiogenesis monitored by expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and tumor microvessel density, in correlation with p53 status, spontaneous apoptosis or disease prognosis in the same group of 70 maxillary sinus SCC patients. Tumor biopsy specimens obtained prior to initiation of treatment were examined for expression of VEGF and bFGF and tumor microvessel density using immunohistological methods. Average vessel density (AVD) (range: 3-75; median: 25) and maximum vessel density (MVD) (range: 4-125; median: 53) were assessed by the number of microvessels stained with anti-CD31 mAb in tumor lesions. VEGF was expressed in 35 (50%) of 70 patients and bFGF was in 43 (61%). Patients with VEGF expression showed significantly higher levels of MVD than those without VEGF expression (57 vs. 38; P=0.019). The VEGF expression was observed more frequently in patients with p53 overexpression and/or mutation than in those with normal p53 status (P=0.048). The MVD inversely correlated with the apoptotic index (AI) defined as the number of single stranded (ss)-DNA-positive cells per 1000 tumor cells (r= -0.23; P=0.022). Patients with neck lymph node and/or distant metastases after surgery showed significantly higher levels of MVD than patients without any metastasis (64 vs. 42; P=0.048). Low histological effectiveness of radiochemotherapy correlated with bFGF expression (P=0.0059). To clarify actual prognostic factors for maxillary sinus SCC, we selected 57 patients treated uniformly with preoperative radiochemotherapy followed by maxillectomy. Kaplan-Meier analysis showed that survival was significantly worse in patients with high MVD (> or =80) than in those with low MVD (<80) (P=0.042). These data suggest that the VEGF expression in association with the p53 overexpression and/or mutations may cause increased microvascularity, decreased spontaneous apoptosis or metastases, while the bFGF expression may be associated with resistance to radiochemotherapy, thereby resulting in poorer prognoses in maxillary sinus SCC. VEGF and bFGF expression and tumor microvessel density in tumor lesions were analyzed in 70 patients with maxillary sinus squamous cell carcinoma. The VEGF expression dependent of p53 overexpression and/or mutations was associated with angiogenesis, decreased spontaneous tumor apoptosis and metastases, while the bFGF expression was associated with resistance to radiochemotherapy, resulting in poor prognosis.     

Downregulation of ABI1 expression affects the progression and prognosis of human gastric carcinoma

Abelson interactor protein-1 (ABI1) is a promising candidate tumor suppressor, and plays critical roles both in the pathogenesis of BCR-Abl-induced leukemia and in the spread of several solid tumors. The expression of ABI1 and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors, including gastric cancer. In this study, we analyzed the correlation between ABI1 expression and the clinicopathological characteristics, tumor progression, and prognosis of patients with gastric carcinoma. Tissue specimens were from 103 gastric cancer patients who underwent gastrectomy in our hospital between January 2000 and December 2007. Among them 59 tumor tissue samples were matched with normal tissue samples. The expression of ABI1 protein was measured using immunohistochemical staining of paraffin-embedded tissue specimens. Meanwhile, quantitative real-time RT-PCR and Western blotting were used to identify the expression of ABI1 in human gastric normal mucosal cell line (GES-1) and gastric cancer cell lines (N87, AGS). We performed a statistical analysis of the potential correlation between ABI1 expression and the patients’ clinicopathological characteristics, 5-year survival, and median survival time. The immunohistochemical staining results of 59 patients showed that ABI1 was expressed in 28.8% (17/59) of gastric cancer tissues, compared to 91.5% (54/59) of normal samples. ABI1 expression in 103 patients was strongly correlated with tumor differentiation, clinical stage, and lymph node status (P < 0.01). The 5-year survival rate was 15.3% in the ABI1-negative group and 63.7% in the ABI1-positive group. Median survival time in the ABI1-negative and ABI1-positive groups was 25.0 months (95% CI: 19.7–30.3) and 74.0 months (95% CI: 54.6–93.3), respectively. There was a significant difference between the two groups (χ² = 10.888, P = 0.001). Furthermore, we found that ABI1 expressed lowly in poor differentiated AGS, whereas highly in GES-1 and well-differentiated N87. Downregulation of ABI1 expression in human gastric carcinoma may play a critical role in tumor progression and in determining patient prognosis. ABI1 may be a useful diagnostic or prognostic molecular biomarker, and might be a potential target for therapeutic intervention.     

胃癌中SS、p53、p21基因蛋白表达与预后的关系

 目的　探讨胃癌中的SS、p5 3、p2 1阳性表达与预后的关系。 方法　采用即用型 -抗 +Envision微波加热免疫组化法对 5 2例胃癌中的SS、p5 3、p2 1表达进行分析。并对 5 2例进行随访。 结果　胃癌中的SS、p5 3、p2 1阳性表达在男女不同阶段均有不同数量的表达。 结论　SS、p5 3、p2 1阳性表达可作为胃癌筛选 ,癌前病变及早期诊断的有用指标 ,可用于临床对病人进行预后判断及疗效观察。     

喉鳞癌中微血管密度和p53表达的研究

目的　探讨喉鳞癌中微血管密度 (microvesseldensity ,MVD)和p5 3表达与肿瘤生长和转移的关系。 方法　应用CD34和p5 3抗体 ,采用免疫组织化学分析 (Envision方法 )对 5 4例喉鳞癌组织中微血管密度及p5 3表达进行了检测 ,并取 10例声带息肉组织对照。结果　 1.喉鳞癌组的MVD和 p5 3表达明显高于声带息肉组 ,差异有统计学意义 (P <0 .0 1)。 2 .p5 3表达与喉鳞癌临床分期 (TNM)和颈淋巴结转移相关 ,p5 3在Ⅰ～Ⅱ期肿瘤中表达率低于Ⅲ～Ⅳ期 (P <0 .0 5 ) ,有淋巴结转移组p5 3表达率高于无淋巴结转移组 (P <0 .0 5 ) ;而 p5 3表达与肿瘤组织病理分级无关 (P >0 .0 5 )。 3.喉鳞癌组织中MVD与颈淋巴结转移相关 ,淋巴结转移组高于非转移组 (P <0 .0 5 ) ;而MVD与喉鳞癌临床分期 (TNM )和病理分级无关 (P >0 .0 5 )。 4 .喉鳞癌组织中MVD与p5 3表达无关 (P >0 .0 5 )。 结论　MVD和 p5 3表达与喉鳞癌生长相关 ,两者可作为预测喉鳞癌发生颈淋巴结转移的指标。     

抑癌基因p53对人胃癌细胞系放射敏感性的作用

目的评价野生型抑癌基因（正常）ｐ５３对人胃癌细胞系放射敏感性的控制作用。方法用流式细胞仪分析４Ｇｙ照射后８和２４小时４种不同ｐ５３状态的人胃癌细胞系细胞周期分布和凋亡的反应。以４Ｇｙ细胞存活份数和１０Ｇｙ照射后的肿瘤生长曲线比较４种细胞的放射敏感性。结果照射４Ｇｙ后８小时和２４小时的ｐ５３正常的ＢＧＣ８２３细胞出现强烈的Ｇ１期阻滞（分别占原细胞总数的６７．９％和６１．１％）,比无照射的该细胞Ｇ１期比例有显著的增高（Ｐ＜０．０５）,并出现明显的预示凋亡的亚Ｇ１峰（ＳｕｂＧ１）,凋亡细胞比例分别达１３．０％和１５．３％;同样条件下其他３种ｐ５３异常的细胞Ｇ１期比例没有显著的变化（Ｐ＞０．０５）,都没有出现亚Ｇ１峰,凋亡细胞比例均为０．０％。ｐ５３正常的ＢＧＣ８２３细胞４Ｇｙ的存活份数明显低于其它３种细胞（Ｐ＜０．０５）;且细胞移植肿瘤１０Ｇｙ照射后比其它３种的生长受到更明显抑制（Ｐ＜０．０５）。结论以上的结果证实了野生型ｐ５３基因促进了照射后肿瘤细胞的Ｇ１期阻滞和凋亡,从而明显地提高肿瘤细胞的放射敏感性。     

RAS AND p53 EXPRESSION IN HUMAN THYROID CARCINOMA

Both benign and malignant nodular disorder of the thyroid gland may give rise to similar symptomatology. Even though clinical background and pathologic criteria may predict prognosis, there are still patients without these adverse prognosis indicators who develop subsequent local invasion or distant metastasis after surgical intervention and eventually succumb to the disease.[1] In recent years it has become apparent that malignant transformation is a result of the accumulation of genetic abno…