食管癌变过程中p53,c—myc,bcl—2表达及其与细 …

探讨食管癌变过程中肿瘤抑制基因Ｐ５３５ 基因ｃ－ｍｙｃ，ｂｃｌ－２的变化及其与细胞凋亡的关系。方法：采用免疫组化法检测２７９例食管粘膜活检组织中ｐ５３－，ｃ－ｍｙｃ，ｂｃｌ－２的表达以及细胞凋亡的关系。结果：从食管正常上皮到基底细胞增生，间变和部，ｐ５３，ｃ－ｍｙｃ－ｂｃｌ－２免疫阳怀表达率及细胞凋亡发生率和细胞凋亡指数均呈升高趋势，而且在同一阶段病变，ｐ５３和ｃ－ｍｙｃ阳性地凋亡指数高于其阴性表     

食管癌变过程中p53、c-myc、bcl-2表达及其与细胞凋亡的关系

目的：探讨食管癌变过程中肿瘤抑制基因ｐ５３和癌基因ｃ－ｍｙｃ、ｂｃｌ－２的变化及其与细胞凋亡的关系。方法：采用免疫组化法（ＡＢＣ）检测２７９例食管粘膜活检组织中ｐ５３、ｃ－ｍｙｃ、ｂｃｌ－２的表达以及细胞凋亡的变化。结果：从食管正常上皮到基底细胞增生、间变和癌，ｐ５３、ｃ－ｍｙｃ、ｂｃｌ－２免疫阳性表达率及细胞凋亡发生率和细胞凋亡指数（ＡＩ）均呈升高趋势，而且在同一阶段病变，ｐ５３和ｃ－ｍｙｃ阳性表达时凋亡指数高于其阴性表达，而ｂｃｌ－２阳性表达时凋亡指数低于其阴性表达。结论：在食管癌变过程中可能有多种肿瘤抑制基因和癌基因参与，细胞凋亡在食管癌变过程中可能有重要的生物学意义。     

脂肪组织源性肿瘤中p53基因的异常

抑癌基因ｐ５３功能丧失或抑制与上皮源性恶性肿瘤的关系,国内外学者研究较多,但对其在软组织恶性肿瘤中,特别是脂肪组织恶性肿瘤中的异常则研究较少,脂肪组织恶性肿瘤中是否存在ｐ５３基因的突变,目前文献报道也不一致。我样拟从蛋白水平到基因水平观察脂肪组织源性肿瘤中ｐ５３的异常,探讨其与脂肪组织源性肿瘤之间的关系。１　材料和方法１．１　材料　组织标本７２例,分别选自中山医科大学病理教研室及中山医科大学附属肿瘤医院病理科。其中正常脂肪组织１０例,脂肪瘤样增生１０例,脂肪瘤１０例,脂肪肉瘤４２例（包括分化良好…     

早期胆囊癌癌基因的表达

目的：研究从慢性胆囊炎，胆囊腺瘤至早期胆囊癌等多阶段发展过程中多种癌基因变化，进一步按摩胆囊癌的发病机理，寻找胆囊癌早期诊断的肿瘤标志物。方法：采用免疫组织化学Ｓ－Ｐ法检测慢性胆囊炎、胆囊腺瘤及早期胆囊癌的ｎｍ２３、ｐ５３、ｒａｓ、ｃ－ｍｙｃ、ｃ－ｅｒｂＢ－２等癌相关基因蛋白的表达。结果：①ｎｍ２３、ｐ５３、ｃ－ｍｙｃ、ｒａｓ及ｃ－ｅｒｂＢ－２基因在胆囊腺瘤及早期胆囊癌中有表达；②着色强度随病变发     

bcl—2,p53蛋白及PCNA表达与横纹肌肉瘤临床病…

目的：研究横纹肌肉瘤（ＲＭＳ）中ｂｃｌ－２、ｐ５３、ＰＣＮＡ表达与其临床病理的相关性。方法：对５０例横纹肌肉瘤进行免疫组化ＡＢＣ法标记。结果：ｂｃｌ－２、ｐ５３基因蛋白和ＰＣＮＡ，发现ｂｃｌ－２、ｐ５３、ＰＣＮＡ阳性表达率分别为２８％、７２％、７０％，其阳性表达与年龄、性别及不同组织类型的ＲＭＳ无关。但民分化程度有关，Ｐ５３、ＰＣＮ在低分化ＲＭＳ阳性率分别为８５％、９５％，显著高于 化ＲＭＳ４２．     

p53和c—myc基因在肝癌和肝硬变细胞中的表达

本实验用免疫组化技术ＡＢＣ法,测定了肝癌和肝硬变细胞中的ｐ５３和ｃ－ｍｙｃ蛋白。结果表明：肝癌组的突变ｐ５３和ｃ－ｍｙｃ基因表达均显著增高（Ｐ＜０．０１）,而肝硬变组中ｐ５３和ｃ－ｍｙｃ的表达与正常组无显著差异,肝硬变组的ｃ－ｍｙｃ表达明显低于肝癌组。以上结果提示,ｐ５３基因发生突变、失活以及ｃ－ｍｙｃ基因激活,导致肝癌的发生。     

c－myc基因和p53蛋白在肝细胞癌中的表达

应用光敏生物素标记ｃ－ｍｙｃ基因探针在石蜡切片上进行原位杂交，ｐ５３蛋白用免疫组织化学ＡＢＣ法对肝癌高发区４２例人原发性肝细胞癌（ＰＨＣ）作定位和定量研究。结果表明ｃ－ｍｙｃ基因和ｐ５３蛋白的表达均位于细胞核内，在ＰＨＣ中异常表达阳性检出率ｃ－ｍｙｃ为７６％、ｐ５３为５５％。而ＰＨＣ中异常表达的分布和强度与癌组织分化程度有关。癌周肝组织中阳性检出率及其强度均低于癌组织。     

c—myc基因和p53蛋白在肝细胞癌中的表达

应用光敏生物素标记ｃ－ｍｙｃ基因探针在石蜡切片上进行原位杂交，ｐ５３蛋白用免疫组织化学ＡＢＣ法对肝癌高发区４２例原发性肝细胞癌（ＰＨＣ）作定位和定量研究。结果表明ｃ－ｍｙｃ基因和ｐ５３蛋白的表达均位于细胞核内，在ＰＨＣ中异常表达阳性检出率ｃ－ｍｙｃ为７６％，ｐ５３为５５％。而ＰＨＣ中异常表达的分布和强度与癌组织分化程度有关。癌周肝组织中阳性检出率及其强度均低于癌组织。     

6种癌基因蛋白产物在甲状腺癌中的表达及意义

目的；探讨甲状腺癌癌变的机理，方法：应用免疫组化Ｓ－Ｐ法于石蜡切片对４３例甲状腺癌，１７例腺瘤，１９例瘤旁甲状腺组织进行了ｃ－ｅｒＢ－２，ｐ２１，ｐ５３，Ｂｃｌ－２，ｃ－ｍｙｃ，ｐ１６癌基因产物的检测。结果：癌组织中均有不同程度，１种或１种以上基因产物表达与腺瘤及瘤旁组织间均存在高度显著性差异（Ｐ〈０．０１），ｃ－ｅｒｂＢ－２，ｐ２１表达随癌组织分化程度增高而增高，ｐ５３表达随癌组织分化程度增高而     

bcl-2、p53蛋白及PCNA表达与横纹肌肉瘤临床病理相关性研究

目的：研究横纹肌肉瘤（ＲＭＳ）中ｂｃｌ－２、ｐ５３、ＰＣＮＡ表达与其临床病理的相关性。方法：对５０例（随访４１例）横纹肌肉瘤进行免疫组化ＡＢＣ法标记。结果：ｂｃｌ－２、ｐ５３基因蛋白和ＰＣＮＡ，发现ｂｃｌ－２、ｐ５３、ＰＣＮＡ阳性表达率分别为２８％、７２％、７０％，其阳性表达与年龄、性别及不同组织类型的ＲＭＳ无关（Ｐ＞０．０５）。但与分化程度有关，ｐ５３、ＰＣＮＡ在低分化ＲＭＳ阳性率分别为８５％、９５％，显著高于高分化ＲＭＳ４２．８％和１４．３％（Ｐ＜０．０５），随访存活１年以内的ｐ５３、ＰＣＮＡ阳性率均为８６．７％，亦明显高于存活超过３年以上的阳性率３３．３％和４１．７％（Ｐ＜０．０５）。而ｂｃｌ－２在低分化ＲＭＳ阳性２０％显著低于高分化７１．４％（Ｐ＜０．０５），随访存活１年以内的阳性率１３．４％明显低于存活超过３年以上的４１．４％（Ｐ＜０．０５）。ｐ５３与ｂｃｌ－２阳性表达呈明显负相关，ｐ５３阳性率越高，而ｂｃｌ－２阳性率越低。结论：ＰＣＮＡ、ｐ５３、ｂｃｌ－２蛋白表达能比较准确地反映ＲＭＳ的生物学特性，ｐ５３、ｂｃｌ－２可作为肿瘤预后显著相关的有效指标。     

病毒性肝炎、癌旁肝硬化和肝癌中bcl-2、c-myc及p63表达

目的：研究肝癌、癌旁肝硬化及病毒性肝炎3种病变中c-myc,bcl-2基因蛋白和p63的表达特征，探讨其对肝癌发生的影响。方法：采用免疫组化（S－P）法检测石蜡包埋组织中c-myc,bcl-2和p63的表达.结果：c-myc,bcl-2蛋白和p63均可表达于胞质和胞核中，c-myc在3种病变中的阳性表达率与表达强度均无差异；bcl-2在3种病变中的阳性表达率虽无差异，但在癌旁肝硬化中，其强阳性率高于肝癌与慢性病毒性肝炎，并在肝癌低分化组阳性表达呈降低趋势；p63阳性主要表达于癌旁肝硬化与肝癌中，并高于慢性病毒性肝炎；c-myc,bcl-2和p63在肝癌中阳性表达的相关性检验显示c-myc与bcl-2阳性率呈正相关（r-0.6742)。结论：c-myc在慢性病毒性肝炎、癌旁肝硬化及肝癌中的持续表达可引起肝细胞增殖和选择性的转化导致癌变。bcl-2的抗凋亡作用在肝癌形成早期并与c-myc具有协同作用。p63在肝癌形成早期可能起促癌作用。     

肝癌组织中ras,c—myc,c—erbB—2和p53的蛋白表达

目的：探讨肝癌的发病机理，方法：应用免疫组化ＳＰ法对４６例肝癌细胞组织及其３８列癌旁中癌基因ｒａｓ，ｃ－ｍｙｃ，ｃ－ｅｒｂＢ－２和抑癌基因ｐ５３基蛋白达作定位研究，结果：在癌组织中的检出率分别为５８．７％，６７．４％，４７．８％和２０．４％，癌旁组织中的检出率分别为３４．２％，４７．４％，４２．１％和７．９％，ｒａｓｐ２１蛋白位于肝细胞和肝细胞的胞浆内ｃ－ｅｒｂＢ－２蛋白位于肝细胞和肝癌细胞的胞浆     

Distinction between lipoma and liposarcoma by MDM2 alterations: a case report of simultaneously occurring tumors and review of the literature

We investigated a lipoma and a well-differentiated/dedifferentiated liposarcoma (WD/DDL), occurring simultaneously in one patient for the possible role of p53 and mdm2 in the molecular oncogenesis of liposarcoma and tumor progression. The hypothesis tested was if there is a continuum in the development from lipoma to liposarcoma. Lipoma was characterized by a lack of p53 mutation, p53 LOH and p53 protein expression, as well as by mdm2 amplification and mdm2 protein expression. p53 mutation and p53 LOH were found neither in the well-differentiated nor in the dedifferentiated parts of the liposarcoma. In contrast, mdm2 amplification and an increase in mdm2 protein expression were found to be associated with malignancy and dedifferentiation, whereas p53 protein expression was only slightly increased. These findings indicate that mdm2 constitutes one of the most common targets for molecular aberration in WD/DDL. We suggest that mdm2 is a marker distinguishing between ordinary lipoma and well-differentiated liposarcoma, and that the genesis of these tumors is different.     

p21ras,p53,c—myc,PCNA在子宫内膜腺癌中的表达

目的：探讨癌基因与子宫内膜腺癌的关系。方法：应用免疫组化ＬＳＡＢ法对３３例原发性子宫内膜膜癌进行Ｐ２１ｒａｓ，ｐ５３，ｃ－ｍｙｃ和ＰＣＮＡ的检测。结果：Ｐ５３表达来７８．８％，Ｐ２１ｒａｓ表达为５１．５％，ｃ－ｍｙｃ表达为８１．８％，ＰＣＮＡ表达为９７％。均明显高于正常增殖期子宫内膜。Ｐ２１ｒａｓ和Ｐ５３在正常子宫内膜无表达，因此比ｃ－ｍｙｃ在子宫内膜腺癌的表达更特异。本研究显示Ｐ５３与子宫内膜腺     

非小细胞肺癌组织中细胞凋亡与p53蛋白表达的定量研究

目的 :观察非小细胞肺癌 (NSCLC)组织中Caspases介导的细胞凋亡与p5 3蛋白表达情况 ,探讨两者之间的相关关系和意义。方法 :临床手术切除的NSCLC标本 4 4例 ,其中鳞癌 2 0例 ,腺癌 2 4例。采用Caspase特异的单克隆抗体M30Cy toDEATH免疫组化染色显示凋亡细胞 ,计算凋亡指数 (AI) ;免疫组化法检测p5 3蛋白表达 ,用显微图像分析系统测定阳性细胞百分率 (P/A)、平均光密度 (AOD)及阳性水平指数 (PLI)。结果 :NSCLC组织中M30阳性率为 2 5 0 % ,肺鳞癌组织的M 30阳性率明显高于肺腺癌组织 (P <0 0 5 )。低分化鳞癌组织的AI高于中、高分化鳞癌 (P <0 0 5 )。NSCLC组织中 p5 3蛋白阳性率为 5 2 2 %。p5 3蛋白的PLI与癌细胞AI之间无直线相关关系。 结论 :在NSCLC组织中存在Caspases介导的细胞凋亡机制 ,且与组织学类型及组织分化程度有关。p5 3蛋白表达与癌细胞凋亡无相关关系 ,提示突变型 p5 3蛋白失去了激活Cas pases而诱导细胞凋亡的作用 ,与肺癌的发生、发展、治疗及预后有关。     

Distinction Between Lipoma and Liposarcoma by MDM2 Alterations: A Case Report of Simultaneously Occurring Tumors and Review of the Literature

We investigated a lipoma and a well-differentiated/dedifferentiated liposarcoma (WD/DDL), occurring simultaneously in one patient for the possible role of p53 and mdm2 in the molecular oncogenesis of liposarcoma and tumor progression. The hypothesis tested was if there is a continuum in the development from lipoma to liposarcoma. Lipoma was characterized by a lack of p53 mutation, p53 LOH and p53 protein expression, as well as by mdm2 amplification and mdm2 protein expression. p53 mutation and p53 LOH were found neither in the well-differentiated nor in the dedifferentiated parts of the liposarcoma. In contrast, mdm2 amplification and an increase in mdm2 protein expression were found to be associated with malignancy and dedifferentiation, whereas p53 protein expression was only slightly increased. These findings indicate that mdm2 constitutes one of the most common targets for molecular aberration in WD/DDL. We suggest that mdm2 is a marker distinguishing between ordinary lipoma and well-differentiated liposarcoma, and that the genesis of these tumors is different.     

An immunohistochemical study of the expression of p53 protein in colon cancer.

A total of 471 cases of colonic adenocarcinomas and 28 cases of colonic adenomas were examined immunohistochemically to evaluate the expression of p53 protein in the light of their relationship with various prognostic factors. A monoclonal antibody, p53 DO-7, was used in the study. Two hundred and fourteen adenocarcinomas (45.5%) showed positive staining for p53, however only three of the adenomas (10.3%) were positive (P < 0.05). p53 was stained to neoplastic nuclei. Adjacent normal mucosal cells were negative. There were no significant correlations between p53 expression and prognostic parameters such as age, sex, gross configuration, modified Astler-Coller stages, microscopic tumor growth patterns, tumor depth, tumor size and lymph node involvements. However, left sided adenocarcinomas (49.3%) expressed p53 more often than right sided adenocarcinomas (35.6%) (P = 0.01). The positive rates were different according to the histologic differentiation; 45.2% in well differentiated, 51.3% in moderately well differentiated, 23.8% in poorly differentiated, and 26.5% in mucinous carcinomas (P = 0.011). The mean survival periods of the p53 positive and negative groups were 29 months and 32 months, respectively (P = 0.385). However, overall survival for patients with grade one and two positive p53 was better than those of grade three and four positive cases (P = 0.028). In conclusion, the result of this multivariate analysis suggests that immunohistochemically strong p53 protein expression (more than 30% of tumor cells) has value in estimating a prognosis for patients with colorectal adenocarcinomas.     

膀胱癌中p53、c—myc和bcl—2的表达及意义

目的：研究癌基因和抗癌基因蛋白产物在膀胱移行细胞癌组织中异常表达与病理分级,临床分期间关系。方法：应用免疫组化S－P法检测96例膀胱移行细胞癌中p53,c-myc和bcl-2的表达水平。结果：96例膀胱移行细胞癌中p53,c-myc和bcl-2的阳性表达率分别为60．4％,68．8％和81．3％,结果表明,p53,c-myc和bcl-2异常表达与膀胱移行细胞癌的分级和分期间差异有统计学意义。结论：p53,c-myc和bcl-2表达在膀胱癌的发生发展中起重要作用。在膀胱癌变过程中,有多种癌基因的变化。     

良恶性脑肿瘤p53蛋白表达与细胞增殖和凋亡的研究

目的探讨脑肿瘤ｐ５３蛋白表达状况对其细胞增殖和凋亡的影响，及这些指标与脑肿瘤组织学类型和恶性程度的关系。方法对１０例对照脑组织和８０例脑肿瘤标本进行原位细胞凋亡及免疫组化标记。结果６９例脑肿瘤（８６．３％）表达ｐ５３蛋白，阳性细胞含量随肿瘤恶性程度升高而增加，对照组全部阴性。各肿瘤组增殖细胞核抗原和Ｋｉ－６７抗原阳性细胞密度均高于对照组，并随肿瘤恶性程度及ｐ５３蛋白表达升高而增加，凋亡细胞密度均低于对照组，并随肿瘤恶性程度及ｐ５３蛋白表达升高而降低。结论提示以上４种指标对评价脑肿瘤生物学行为有参考价值，脑肿瘤ｐ５３蛋白表达和功能异常与其细胞增殖及凋亡失衡有关，可能是原发性和转移性脑肿瘤发生发展的重要因素。     

Aberrant expression of p53 gene product in malignant melanoma.

According to the current concept of carcinogenesis, the alterations of p53 tumor suppressor gene have been the most frequently detected in both human cancer cell lines and cancer tissues freshly isolated. This study was conducted to investigate the p53 gene alteration in malignant melanoma. Nineteen tumor tissues were obtained from 19 patients with malignant melanoma and examined for the expression of p53 protein by immunohistochemical staining with mouse monoclonal anti-p53 antibody, NCL-p53-DO-7. Twelve out of 19 cases (63%) showed positive reactions for p53 protein: 26, 21 and 16% of which had low, intermediate and high reactivity, respectively. p53 alteration more frequently expressed in female (10/12) than male patients (2/7) with malignant melanoma (p < 0.05). The incidence of expression of p53 protein was compared according to the stages and the sites of tissue obtained. The positive rate for p53 protein was not significantly different between the stages. The positive rates for p53 protein were five out of five (100%), one out of two (50%) and six out of twelve (50%) in tissues obtained from the metastatic, lymph node, and primary sites, respectively. The difference in the positive rates, however, is not statistically significant. These results suggest that p53 gene is a frequent target for mutation in the development of malignant melanoma.