Immunohistochemical detection of P73 product in brain glomas

Objective: To elucidate the role of p73 in the genesis or development of glioma. Methods: P73 and p53 expression of 63 gliomas were detected by immunohistochemistry. Results: Out of the 63 gliomas, 17 cases appeared p73 positive. The positive-rate in high grade gliomas was higher than that in low grade gliomas (x ²=4.75, P<0.05). Among the 17 cases with p73-positive gliomas, 12 cases overexpressed p53 protein. Conclusion: Overexpression of wild p73 may involve in the genesis or development of glioma.     

鼻咽癌组织中p73蛋白表达及其与临床病理特征的关系

目的：探讨鼻咽癌组织中p73蛋白的表达及其与临床病理特征的关系。方法：应用免疫组化S－P法，检测p73蛋白在83例鼻咽癌组织和20例鼻咽黏膜慢性炎症组织中的表达以及p53蛋白在鼻咽癌组织中的表达情况。结果：83例鼻咽癌组织中p73蛋白表达阳性率（50．6％）较20例鼻咽 黏膜慢性炎症组织（15．0％）明显增高（P＜0．05），I，Ⅱ期鼻咽癌组织p73蛋白表达阳性率（27．8％）低于Ⅲ，Ⅳ期（56．9％）P＜0．05，P73蛋白表达阳性率与患者性别，颈部淋巴结转移，局部区域复发，远处转移放疗后5年生存率无关，P53蛋白阳性率为51．8％，其表达与P73蛋白表达无相关性（P＞0．05），结论：P73蛋白在鼻咽癌组织中的表达水平明显上调，其表达在肿瘤的发生发展中起重要作用。     

P21和P53蛋白在食管癌表达的免疫组化研究

作者用免疫组化ＡＢＰＡＰ法观察４０例食管癌及癌旁组织的ｒａｓ癌基因产物Ｐ２１和癌基因Ｐ５３蛋白的表达。结果显示：Ｐ２１和Ｐ５３蛋白阳性表达分别有２４例和８例（阳性率为６０％和２０％）、。高分化鳞癌以Ｐ２１蛋白表达为主，低分化鳞癌则以Ｐ５３蛋白表达较多；而粘液表皮样癌和腺鳞癌几乎均有超表达现象。癌旁粘膜两种蛋白表达的阳性率明显低于癌组织。Ｐ２１和Ｐ５３蛋白阳性病例，其淋巴结转移率有显著的差异（Ｐ＜：０．０５）。作者认为，在食管癌病人中，检测其癌组织的Ｐ５３蛋白比Ｐ２１蛋白更加有助于了解其生物学特性及预测其预后     

DELETION AND 5'CPG ISLAND METHYLATION OF p15 GENE IN BRAIN GLIOMA

P15geneisananothertumorsuppressorgene,whichislocatedongpZIandadjacenttopl6gene.Itencodesplsproteinthathasbiochemicalfunctionssimilartothoseofp16protein.Therehavebeenreportsaboutabnormalityofplsgeneinbrainglioma.['-']Inthisstudy,wedetecteddeletionand5'CPGislandmethylationofp15genein56casesofbraingliomabythemethodsofPCRandPCR-basedmethylationtoinvestigatethecorrelationbetweenabnormalityofplsgeneandoccurrenceormalignantprogressionofbrainglioma.MATERIALSANDMETHODSSpecimensFifty-sixfre…     

肺癌组织抑癌基因P53异常分析

Ｐ５３基因５－８外显子ＰＣＲ产物的ＤＮＡ序列分析及石蜡包埋组织Ｐ５３鼠抗人单克隆抗体（Ｄｏ－１）免疫组化分析发现：５７例原发性肺癌中３７例有Ｐ５３蛋白积累。ＤＮＡ／ＰＣＲ产物直接测序发现：９／１２例小细胞肺癌（ＳＣＬＣ），８／１５非小细胞肺癌（ＮＳＣＬＣ）Ｐ５３基因突变，错义突变为１２／１７，Ｇ→Ｔ突变为６／１７。免疫组化发现：１１／１９例ＳＣＬＣ，１９／３７例ＮＳＣＬＣ Ｐ５３蛋白染色阳性。４／     

P73 functionally replaces p53 in Adriamycin-treated, p53-deficient breast cancer cells

p53-Related genes, p73 and p63, encode 2 classes of proteins, TA-p73/p63 and DeltaN-p73/p63. TA-p73/p63 demonstrate p53-like properties including gene transactivation and cell death promotion, whereas DeltaN-p73/p63 lack these p53-like functions. Although p53-deficient cancer cells are often less responsive to chemotherapy, they are not completely drug resistant, suggesting that other apoptotic pathways are at work. Here, we compared for the first time to our knowledge p73 and p63 activation in various breast cancer (BC) cell lines after Adriamycin (ADR) treatment, an agent considered as mandatory in breast cancer chemotherapy. Our study was carried out using 1 p53-proficient BC cell line (MCF7 cells) and 3 BC cell lines deficient in p53 response (MCF7/ADR(IGR), MDA-MB157 and T47D) after ADR-induced genotoxic stress. We report that in cells with no p53 response after ADR treatment, TAp73, but not TAp63 or DeltaN-p73/p63, may replace p53 in triggering not only apoptosis but also cell cycle arrest or DNA repair effectors such as p21, GADD45, 14-3-3sigma and p53R2. We also demonstrate that TAp73 siRNA inhibits the accumulation of TAp73 in response to ADR treatment in MDA-MB157 cells and confers protection against ADR. ADR-induced downregulation of the DeltaNp73 isoform in the T47D cell line with nonfunctional mutant p53 further supports anti-apoptotic function of the isoform antagonistic to both p53 and TA-p73/p63. Exogenous TAp73 and DeltaNp73 overexpression in p53-response-deficient cell lines further confirms these results. cDNA microarray techniques demonstrated that the cellular response induced by p73 during ADR treatment could involve specific genes.     

P53、P63、P73蛋白在骨肉瘤中的表达及相关性研究

目的 研究P53、P63、P73蛋白在骨肉瘤中的表达,探讨它们之间的相关性及其在骨肉瘤发生发展中的可能作用。方法 应用免疫组织化学方法和图像分析技术检测52例骨肉瘤标本P53、P63和P73蛋白的表达。结果 骨肉瘤P53、P63、P73蛋白表达水平高于正常骨组织,差别均有显著意义(P<0.01),三者表达与患者性别、年龄及病理类型无关;P53、P63、P73蛋白在骨肉瘤病理Ⅰ级的表达明显低于Ⅱ、Ⅲ级(P<0.05);P73蛋白过表达与肿瘤直径大小及侵犯转移有关(P<0.05),P63与P53蛋白,P73蛋白与P53蛋白表达之间存在着正相关(r=0.328,0.346,P<0.05)。结论 P53、P63、P73蛋白以高表达方式参与骨肉瘤发生发展,并与骨肉瘤进程密切相关。p53基因突变可能与p63、p73基因表达异常有关。     

Wild type p73 overexpression and high-grade malignancy in breast cancer

The overexpression of wild type p73 is the most frequent alteration of p73 in malignancies. We investigated, in 70 breast carcinomas, p73 mRNA expression and its relationship to p53 mutations, determined by an immunohistochemical method, and loss heterozygosity (LOH) status of the 1p36 region, together with its possible implication in the pathogenesis of breast carcinomas. LOH, amplifying DNA by PCR using 5 markers, of 1p36 region (one intragenic to p73 gene) was found in 17% of cases but no significant correlation was observed with p73 overexpression. p53 positive immunostaining was present in 33% of breast carcinomas, and these exhibited a statistically significant relation with p73 overexpressed tumors. Overexpression of p73 mRNA was observed in 19 tumors (27%). The analysis of cases with p73 overexpression and cases with normal mRNA expression, in terms of age and pathologic characteristics of the tumors showed a significant association of p73 overexpression and tumors with lymph node metastases, vascular invasion and higher pathologic stage. These results suggest that p73 overexpression is a molecular alteration that could be implicated in the tumorigenesis of breast carcinomas and, eventually, in a poor clinical behavior.     

结肠癌淋巴结微转移免疫组化检测及其预后关系

目的　探讨结肠癌淋巴结微转移免疫组化检出率及淋巴结微转移与临床预后的关系。　方法　应用抗细胞角蛋白（ＣＫ） 和癌胚抗原（ＣＥＡ） 单克隆抗体,对６８ 例结肠癌（Ｄｕｋｅｓ′Ｂ期） 根治术后经病理常规检查为转移阴性的５８４ 枚淋巴结进行免疫组化（ＡＢＣ法）检测,结合随访资料进行临床预后分析。　结果　６８ 例转移阴性的５８４枚淋巴结中,１３ 例（１９－１ ％ ,１３６８）２９ 枚（５－０ ％ ,２９５８４）淋巴结中发现微小转移的癌细胞,其中１１ 例５ 年内因局部复发和远处转移死亡。５５ 例免疫组化检测阴性的患者仅３ 例复发。免疫组化诊断微转移阳性和阴性组５ 年复发率分别是８６－６％ （１１１３） 和５－５％ （３５５）。两组病人差异非常显著（ Ｐ＜ ０－００１）。　结论　应用肿瘤特异性抗体检测常规病理检查阴性的淋巴结有助于发现微小转移的癌细胞,对估计临床预后,指导治疗有重要意义     

Targeting p73 in cancer

p73 is a member of the p53 family of tumor suppressors. Transactivating isoforms of p73 (TAp73) have p53-like, anti-proliferative and pro-apoptotic activities that are crucial for an efficient chemotherapy response. In line with this, genetic studies in mice have confirmed that TAp73 acts as a tumor suppressor. However, in contrast to p53, which is commonly inactivated in human cancer by point mutations, the TP73 gene is almost never mutated. Instead, the tumor suppressor activity of TAp73 is inhibited through a variety of mechanisms including epigenetic silencing and complex formation with inhibitory proteins. All these mechanisms have in common that they are in principle reversible and therefore amenable to therapeutic intervention. Here, we will review how tumor cells control the tumor suppressor activity of TAp73 and discuss possible strategies targeting p73 for reactivation.     

P53蛋白在恶性肿瘤组织中的表达及其意义

应用抗Ｐ５３蛋白单克隆抗体和ＡＢＣ方法，对１８种不同组织来源的９１例肿瘤冰冻切片进行了免疫组化检测，结果在５５例恶性肿瘤中２８例呈阳性，阳性率为５０．９％，３６例良性肿瘤中仅１例阳性，阳性率为２．８％，在良，恶性肿瘤之间阳性有显著差异（Ｐ〈０．０１），结果表明，Ｐ５３蛋白的异常表达是恶性肿瘤常见的基因变化，Ｐ５３基因的改变可能为人类多种肿瘤恶性转化的原因之一。     

应用生物素标记探针原位检测星形细胞瘤组织中p53基因

采用核酸分子原位杂交技术检测３２例星形细胞瘤患者瘤组织中ｐ５３基因。结果显示１５例患者瘤细胞中出现ｐ５３基因的杂交颗粒，阳性率为４６．９％。认为约半数的星形细胞瘤的发生与ｐ５３基因有关。     

Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic lymphocytic leukemia

The p73 protein shares structural and functional similarities with thetumour-suppressor p53, but its role in neoplastic transformation is unknown.Alternative splicing leads to the expression of at least nine p73 C-terminalmRNA splice variants (, , , , , , ,1, ). In this survey, we analyse the expression of p73 byreal-time quantitative RT–PCR, its known C-terminal variants with anRT–PCR-Southern technique and by Western blot in samples of 51 patientswith B-CLL, normal B lymphocytes from eight individuals, and fivehaematopoetic cell lines. p73 protein expression positively correlatedwith higher risk B-CLL stages (P = 0.046). Total p73 mRNAexpression was higher (P = 0.01) and p73 protein morefrequently detected (P = 0.008) in B-CLL compared with normalCD19+–B-lymphocytes. p73 C-terminal mRNA variants were expressed bothin B-CLL and in normal B-lymphocytes, but their expression was biased sincethe (P = 0.041), the (P <0.001), and the variant (P = 0.033) prevailed in normalB-lymphocytes. In summary, we conclude that the accumulation of p73, theexpression pattern of particular p73 variants and its link to progression mayplay a distinct role in the molecular pathology B-CLL.     

p53和p16在胆囊癌中的表达

目的探讨抑癌基因ｐ５３和ｐ１６改变对胆囊癌发生的作用。方法采用免疫组化方法检测３４例胆囊癌和２６例慢性胆囊炎标本中ｐ５３和ｐ１６的表达。结果慢性胆囊炎标本中ｐ５３１例阳性，阳性率为３．９％。胆囊癌中ｐ５３有１７例阳性，阳性率为５０％。两者表达差异有显著性（Ｐ＜０．００１）。ｐ１６在慢性胆囊炎标本中有１４例阳性，阳性率为５３．８％，胆囊癌中２９例阳性，阳性率为８５．３％，明显高于慢性胆囊炎（Ｐ＜０．０２）。结论ｐ５３过表达与胆囊癌发生之间存在一定的联系，但对胆囊癌的发展、侵袭影响不大。ｐ１６在胆囊癌发生中可能受某些癌基因的反馈调节而过度表达，其作用机制尚不十分清楚。     

胃癌P53基因突变和蛋白表达的研究

为了解中国人胃癌Ｐ５３基因突变情况，应用银染聚合酶链反应－单链构象多态（ＰＣＲ－ＳＳＣＰ）技术对Ｐ５３基因第５、６、７、８外显子进行检测。对来自癌组织ＤＮＡ和癌旁正常组织ＤＮＡ的ＰＣＲ－ＳＳＣＰ电泳带迁移作对比分析，发现３７例胃癌中，１１例胃癌样品电泳带迁移异常，依据ＤＮＡ单链构象与分子电泳迁移的关系，研究结果表明：胃癌Ｐ５３基因５－８外显子的突变率为３０％。微波处理ＡＢＣ法检测突变型Ｐ５３蛋白表     

胃癌中Fas/FasL、p27的免疫组化研究

目的 :研究 Fas/ Fas L、p2 7在胃癌及正常组织中的表达 ,并探讨其与临床病理学特征的关系。方法 :利用免疫组化法对 10 0例胃癌组织及 10例正常胃组织的 Fas/ Fas L、p2 7表达进行检测 ,分析上述组织中 Fas/ Fas L、p2 7、PCNA表达的差异。结果 :肿瘤组织与正常组织 Fas的阳性表达率 (62 % vs10 0 % )和 Fas L 的阳性表达率 (86% vs10 % )差异均有显著性 (P<0 .0 5)。而不同分化的肿瘤组织中 Fas/ Fas L表达差异无显著性 (P>0 .0 5)。 p2 7在肿瘤组织与正常组织中的高表达率分别为 54%和 10 0 % ;p2 7在两组织中的表达差异均有显著性 (P<0 .0 5) ,且 p2 7表达与胃癌的分化程度、淋巴结转移和 TNM分期显著相关。结论 :胃癌中存在 Fas表达的下调和 Fas L表达的上调 ,Fas/ Fas L 系统可能参与了胃癌细胞的免疫逃避机制 ;p2 7蛋白的表达与胃癌的临床病理学特征密切相关 ,可能是一个预测胃癌预后的重要指标。     

p53基因蛋白在肺癌组织中的表达及其意义

为了探索ｐ５３蛋白与肺癌的组织学类型、淋巴结转移等因素的关系。用免疫组织化学方法检测了５４例肺癌ｐ５３蛋白的表达。结果表明，阳性表达率为肺鳞癌２７．３％（６／２２），腺癌３６．８％（８／２０），腺鳞癌１００％（１／１），小细胞癌７５％（９／１２）。随着分化程度的不同表达率亦不同，高中低分化肺癌分别为３５．７％、４２．９％、４５．５％。淋巴结有无转移的患者ｐ５３蛋白表达率分别为４８．４％和３４．８％，各组之间的差异较显著。提示：ｐ５３蛋白表达可以反应肺癌细胞的活性，为研究肺癌的生物学行为提供了一个良好的标志物。