p53、c-erbB1、c-myc和p16基因蛋白产物在人脑胶质瘤中的表达

目的为了探明癌基因ｃ－ｅｒｂＢ１、ｃ－ｍｙｃ，抑癌基因ｐ５３和ｐ１６在胶质瘤发生发展中的作用，以及上述基因蛋白检测对胶质瘤诊断、分级的临床意义。方法用免疫组化ＡＢＣ法检测４种癌基因蛋白产物在６５例人脑胶质瘤中的表达，并分析与胶质瘤病理分级间的关系。结果ｐ５３、ｃ－ｅｒｂＢ１、ｃ－ｍｙｃ过度表达率随胶质瘤级别升高而逐渐升高，前两者在胶质瘤良性组和高度恶性组间差异有显著性（Ｐ＜０．０５）；ｐ１６在高度恶性组表达缺失率高于其它组，但差异不显著；４种癌基因、抑癌基因在胶质瘤中有协同表达。结论上述４种基因在胶质瘤的形成和发展中发挥着不同程度的作用，对ｐ５３、ｃ－ｅｒｂＢ１基因蛋白的检测或多种癌基因蛋白联合检测，对胶质瘤的病理分级和预后判断有积极的意义。     

p53基因蛋白异常表达在胃癌中的意义

目的：探讨ｐ５３基因表达异常的意义。方法：用免疫组织化学方法研究ｐ基因蛋白在胃癌中的表达。结果：７２例胃腺癌中３６例阳性，高分化腺癌和低分化腺癌Ｐ５３阳性率明显高于粘液，不同浸润深度的癌细胞与癌细胞Ｐ５３阳性程度有关，在淋巴结转移组和无转移组间Ｐ５３阳性率和阳性程度均无程度差异。病人的生存时间与Ｐ５３阳性我明显的相关性，癌旁肠上皮化生和异型增生腺体全部为阴性。结论．Ｐ５３异常 表达是细胞癌变的标志     

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。     

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。     

膛胱移行细胞癌中c—erbB—2,p53及p16蛋白的表达

目的 探讨膛胱癌组织中ｐ１６、ｃ－ｅｒｂＢ－２和ｐ５３蛋白表达与胱癌病理分级、临床分期和转移的关系。方法 应用免疫组化ＳＰ法对７５例膛胱癌组织中ｐ１６、ｐ５３及ｃ－ｅｒｂＢ－２蛋白表达进行检测。结果 ７５例膛胱癌中ｐ１６、ｐ５３及ｃ－ｅｒｂＢ－２的阳性率分别为４１．３％（３１／７５）、４４．０％（３３／７５）和４０．０％（３０／７５）,ｐ１６和ｃ－ｅｒｂＢ－２蛋白在膛胱癌中的阳性率与肿瘤中的阳性率     

p53,p21和p16基因蛋白在膀胱癌中表达意义

１材料和方法１．１材料收集牡丹江市第一人民医院有完整随访记录的膀胱癌患者５０例，年龄３５～７６岁，其中男性４３例，女性７例。所有标本均经１０％福尔马林固定，常规石蜡包埋，４μｍ厚连续切片，另取６例正常膀胱标本作对照。全部病例术前均未作化疗，病理分级按...     

胃癌P-糖蛋白和p53蛋白协同表达的意义

目的：探讨P糖蛋白和p53蛋白在胃癌中的协同表达意义。方法：应用免疫组化方法检测259例术前未进行化疗的胃癌组织中多药耐药基因产物P 糖蛋白的表达。结果：P－gp和p53在胃癌中的表达分别为26．25％（68／259）和37．01％（96／259）。P－gp表达与胃癌的组织学类型、浸润深度和淋巴结转移状况无关（P＞0．05）;p53除与淋巴结转移状况有关外（P＜0．001）,与组织学类型和浸润深度无关（P＞0．05）。P-gp在p53阳性的病例中的表达明显高于p53阴性的病例,即75％P－gp阳性的病人同时伴有p53阳性。结论：P-gp和p53常协同表达于胃癌组织中,并可作为胃癌病人预后判断和临床耐药的一个可靠指标。     

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。     

癌基因c-erbB2、c-myc和抑癌基因p16、p53在口腔鳞癌中的蛋白表达及其协同作用

目的：探讨癌基因c—erbB2、c-myc和抑癌基因p16、p53在口腔鳞癌(OSOC)中的蛋白表达及其协同作用。方法：用免疫组化结合图像分析对口腔鳞癌中4种基因的蛋白表达进行定性、定位、定量研究。结果：口腔鳞癌中c—erbB2、c—myc、p16和p53的蛋白表达阳性率依次为46．67％、60％、86．67％和63。33％。肿瘤部位不同,erbB2蛋白表达有显著性差异;腭癌和口底癌中的erbB2蛋白表达都明显高于唇癌和牙龈癌中的erbB2表达。c-myc蛋白表达与p16蛋白表达之间具有显著性相关。结论：以上4种基因的蛋白表达增高在口腔鳞癌发生发展中具有重要作用,c—erbB2蛋白过表达在腭癌和牙龈癌中具有更重要的意义;c—myc和p16蛋白表达间具有一定的内在联系。     

c-myc、p53和p16的表达及GNAS1基因突变在骨的纤维结构不良中的意义

目的 检测c-myc、p53和p16蛋白在骨的纤维结构不良(FD)中的表达及其意义,检测FD中GNAS1基因第8外显子突变,探讨FD的病变性质.方法 采用免疫组织化学SP法检测35例FD(包括1例FD恶变,1例Mazabraud综合征)及20例对照组(10例骨痂、10例骨肉瘤)中c-myc、p53和p16蛋白表达.采用基因组DNA抽提、PCR扩增及基因测序的方法检测35例FD中GNAS1基因第8外显子突变情况.结果 91%(32/35)FD中检测到c-myc蛋白表达,与阴性对照组相比差异具有统计学意义(P=0.001).p53阳性表达仅出现于1例FD合并骨肉瘤变病例中.p16蛋白在34例FD中阳性,与阳性对照组相比差异具有统计学意义(P=0.001).35例FD中,12例GNAS1基因第8外显子DNA扩增成功,其中2例(1例Mazabraud综合征的FD;1例单骨性FD)检测到GNAS1基因突变.结论 c-myc可能是除c-fos外的又一FD相关的原癌基因,p16基因的异常表达在FD的形成过程中可能起重要作用,p53蛋白过表达有助于FD恶变的预测及预后的判断.FD中存在有GNAS1的基因突变.FD是多种因素共同作用导致的骨成熟障碍的肿瘤性病变.     

Expression of p16, Rb, and p53 proteins in squamous cell carcinomas of the anorectal region harboring human papillomavirus DNA.

Human papillomavirus (HPV) has been implicated as an etiologic agent for the development of squamous cell carcinoma of the anorectal region. It has been shown that the HPV E6 and E7 oncoproteins are able to inactivate the tumor suppressor functions of p53 and Rb. In cervical and head and neck cancers, HPV infection is also associated with an overexpression of p16, a cyclin-dependent kinase inhibitor. The expression of these cell cycle regulators in squamous cell carcinomas of the anorectal region has not been well studied. In the current study, 29 cases of squamous cell carcinoma of the anorectal region were immunohistochemically examined for the expression of p16, Rb, and p53 proteins. Tumor cell DNA was also extracted from paraffin blocks and subjected to broad-spectrum HPV DNA testing and typing. The results show that the tumor cells exhibited a strong and diffuse nuclear stain (with some cytoplasmic positivity) for p16 in all 29 cases (100%). The adjacent nonneoplastic squamous epithelium or colonic mucosa, in contrast, was completely negative. Loss of Rb nuclear staining in tumor cells was observed in 20 cases (69%). The p53 protein was essentially undetectable, with only 6 cases containing <10% positive cells. HPV DNA was detected in every case (100%), with 25 cases (86%) harboring Type 16. In addition, almost identical results were obtained in 12 HPV-positive squamous cell carcinomas of the upper aerodigestive tract. This was in marked contrast to those of HPV-negative tumors, where positive p16 staining and loss of Rb expression were seen in only 2/21 (10%) and 1/21 (5%) cases, respectively. These observations indicate that overexpression of p16 and loss of Rb nuclear staining are commonly associated with high-risk HPV infection, which may serve as useful surrogate biomarkers for identifying squamous cell carcinomas harboring HPV DNA.     

Expression of cell cycle-regulatory proteins, MIB-1, p16, p53, and p63, in squamous cell carcinoma of conjunctiva: not associated with human papillomavirus infection

Squamous cell carcinoma (SCC), the most common primary malignant tumor of the conjunctiva, has a variable clinical presentation and immunohistochemical profile. Abundant cell cycles exist, including MIB-1 (Ki67 antigen), p16, p53, and p63, within the conjunctiva SCC. This investigation first reports the expressions of cell cycle markers in SCC. A retrospective study was conducted between December 1976 and June 2004, comprising 13 consecutive patients with conjunctiva SCC who were treated with surgical excision. Detailed clinical parameters were also reviewed. Overexpression of MIB-1, p16, p53, and p63 genes were studied by immunohistochemistry. Genechip containing 39 subtypes was used to elucidate human papillomavirus (HPV). The study group contained 13 (100%) men, with a mean age of 68±18 years and follow-up period of 20±17 months. The sample included four (33%) SCC located in the left eye and two (17%) recurrent SCC. Overexpression of the p53 and p63 was considerably higher than that of the p16 (P<0.01). HPV DNA was not detected in any of the 13 cases. This work first examined the immunohistochemical overexpression of cell cycle (MIB-1, p16, p53, and p63) in SCC. This investigation then showed that the expression of cell cycles in SCC was associated with key tumor clinicopathological features. This approach can help distinguish the potential roles of cell cycle in the development of SCC.     

星形细胞瘤中PTEN、p16和p53蛋白表达与预后的关系

目的探讨星形细胞瘤组织中PTEN、p16和p53蛋白表达与患者预后的关系。方法采用EnVision二步法免疫组化技术,检测80例星形细胞瘤组织中PTEN、p16和p53蛋白表达,并结合随访资料进行统计学分析。结果80例中PTEN和p16蛋白的表达缺失分别为17例（21％）和35例（44％）,p53蛋白过度表达为51例（63％）。61例患者获随访结果,随访时间13～47个月,其中29例健在,32例死亡,总生存率为47％;死亡病例中Ⅲ～Ⅳ级患者29例,占9l％。单因素分析示PTEN和p16阳性表达、肿瘤级别低、年龄〈50岁,预示患者预后较好（P〈0．05）;多因素分析结果提示肿瘤级别越高。患者生存期越短（P〈0．001）。结论星形细胞瘤患者的预后与PTEN、p16和p53蛋白的表达有关,PTEN、p16蛋白的丢失预示患者预后较差,3种基因蛋白的表达与肿瘤级别密切相关。     

Expression of c-erbB2, p53, Bcl-2, Bax,c-myc and Ki-67 in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast

Molecular evidence has recently suggested a number of different pathways leading to the development of ductal carcinoma of the breast. The links between atypical ductal hyperplasia and low-grade ductal carcinoma in situ and lobular neoplasia and lobular carcinoma are well known pathologically, but high-grade in situ and invasive carcinomas appear to have a different biological oncogenetic pathway. Morphologically there is a similarity between apocrine cells and some cases of high-grade ductal carcinoma. In order to investigate this possibility a number of different biological markers known to occur in high-grade breast carcinomas were assessed in both apocrine metaplasia (APM) and a putative premalignant lesion called apocrine change within sclerosing adenosis (AA). In 64 cases of APM and 18 cases of AA we examined for expression of c-erbB2, p53, Bcl-2, Bax, c-myc and Ki-67 proteins using immunocytochemistry. c-erbB2 expression was seen in 55.6% of AA cases and in 10.9% of APM cases. p53 expression was detected in 27.8% of AA cases but only 1.6% of APM cases. All cases of AA and APM were negative for the anti-apoptotic protein Bcl-2, but all the APM and 33.3% of AA cases showed cytoplasmic positivity for Bax, a pro-apoptotic protein. All the cases of AA and APM were positive for c-myc oncoprotein, however, the mean percentage of nuclear positivity was 50% in AA and 37% in cases of APM cases. The mean percentage positivity for Ki-67, a proliferation associated antigen, was 3.6% in AA and 1.3% in APM. The results indicate that a subset of breast lesions containing APM epithelium show abnormal oncoprotein and apoptosis-related protein expression and have a higher proliferation rate.     

p-MAPK、cyclinD1和p53蛋白在大肠癌中的表达及其相关性

目的：检测ｐ－ＭＡＰＫ、ｃｙｃｌｉｎＤ１和ｐ５３蛋白在大肠癌中的表达，并探讨其相关性。方法：免疫组织化学Ｓ－Ｐ法。结果：１４０例大肠癌中ｐ－ＭＡＰＫ、ｃｙｃｌｉｎＤ１和ｐ５３蛋白的阳性表达率分别为９２．９％（１３０／１４０）、８７．１％（１２２／１４０）和６６．４％（９３／１４０）；５０例相应癌旁肠粘膜中阳性表达率分别为４．０％（２／５０）、６．０％（３／５０）和２．０％（１／５０）。三者阳性表达     

c—erbB—2和p53基因表达与胃癌浸润转移的关系

目的：探讨胃癌组织中c-erbB-2和p53基因的表达与胃癌发生和浸润转移的关系。方法：应用荧光原位杂交技术对55例胃癌的常规石蜡标本进行检测,结果：c-erbB-2和p53基因表达的阳性率分别为36．6％和45．45％,其中在肠型和弥漫型胃癌中,c-erbB-2和p53阳性率分别为51．615和16．67％,p53阳性率分别为25．81％和70．83％,两种基因在两型间的差异有显著性意义（P＜0．05）,c-erbB-2和p53基因表达与胃的组织分级有关（分别为P＜0．05及P＜0．01）c-erbB-2和p53基因表达与胃癌的浸润深度有相关性（分别为P＜0．01及＜0．05）,c-erbB-2;基因表达与胃癌的淋巴结内转移有显著性意义（P＜0．05）,结论：c-rebB-2和p53基因有助于确定胃癌的生物学行为。     

Immunohistochemical detection of p53 and c-myc proteins in canine mammary tumours

The objectives of this study were to detect by immunohistochemical means, nuclear accumulations of p53 and c-myc proteins in mammary tumours of dogs. Moderate or intense p53 protein nuclear labelling was shown by each of five osteosarcomas. In contrast, focal immunoreactivity was shown by three of five adenocarcinomas and two of three malignant myoepitheliomas. Six benign mixed tumours and three myoepitheliomas showed no detectable immunoreactivity. On the other hand, three patterns of c-myc protein nuclear reactivity were observed in these tumours. Osteosarcomas, adenocarcinomas, malignant myoepitheliomas and myoepitheliomas showed intense or moderate reactivity. In benign mixed tumours, the epithelial component showed moderate or intense reactivity, and the myoepithelial component showed focal or moderate reactivity. These results demonstrated that p53 protein was expressed only in the osteosarcomas, but that c-myc expression was detectable in both the epithelial and myoepithelial components.