p53、c-erbB-2癌基因蛋白表达与胃癌生物学行为的关系

目的：探讨ｐ５３、ｃ－ｅｒｂＢ－２表达与胃癌生物学行为的关系。方法：利用微波免疫组化方法研究７０例胃癌及２０例胃癌前病变ｐ５３、ｃ－ｅｒｂＢ－２蛋白的表达。结果：正常胃粘膜和肠化生上皮ｐ５３及ｃ－ｅｒｂＢ－２均阴性，中、重度异型增生及胃癌组织中ｐ５３阳性率分别为１５．０％和５１．４％。ｃ－ｅｒｂＢ－２阳性率分别为１０．０％和４０．０％。ｐ５３与胃癌组织学类型、组织发生及分化程度等有关（Ｐ＜０．０５），而ｃ－ｅｒｂＢ－２则与胃癌分化程度、胃癌浸润深度等有关（Ｐ＜０．０５）。在低分化腺癌癌巢边缘部，硬癌内呈浸润性生长的细胞以及脉管内转移性癌栓等处，除了癌细胞核内ｐ５３表达较强外，胞浆也呈弥漫性染色，表明胞浆阳性的癌细胞具有更强的侵袭性。在非浸润进展组或随患者生存期的延长，胃癌组织内ｐ５３及ｃ－ｅｒｂＢ－２的阳性率有下降的趋向。结论：ｐ５３可作为临床筛选胃癌、癌前期病变以及进行早期诊断的有用指标，ｐ５３与ｃ－ｅｒｂＢ－２一起可用于判断胃癌预后，监测病情     

c─erbB─2、ras p21及p53在大肠癌表达的免疫组化研究

对４８例大肠癌连续切片进行ｃ─ｅｒｂＢ─２、ｒａｓｐ２１及ｐ５３３种癌相关基因产物的免疫组化ＡＢＣ法及ＡＰＡＡＰ－ＩＧＳＳ双重标记研究，结果表明：（１）癌相关基因ｃ─ｅｒｂＢ─２、ｒａｓｐ２１和ｐ５３阳性表达率在癌组织分别为５０．２％（２５／４８）、４３．８％（２１／４８）和５４．２％（２６／４８）；癌旁粘膜分别为２５％（１２／４８）、１８．８（９／４８）和２０．８％（１０／４８）；而在＂正常＂结肠粘膜则分别为１２．５％（６／４８）、６．３％（３／４８）和０．（２）有２种以上癌相关基因产物同时表达者在癌组织中有２６例（５４．２％）．在癌旁粘膜有５例（１０．５％），而在正常粘膜则未见有２种癌相关基因同时表达，（３）癌组织中ｃ─ｅｒｂＢ─２＋ｐ２１、ｃ─ｅｒｂＢ─２＋ｐ５３、ｐ２１＋ｐ５３及ｃ─ｅｒｂＢ─２＋ｐ２１＋ｐ５３同时表达者分别为２．１％、１２．５％、１６．７％及２２．９％，（４）ＡＰＡＡＰ－ＩＧＳＳ双重免疫标记结果表明，单一癌细胞可同时表达２种癌基因产物。上述结果提示：ｃ─ｅｒｂＢ─２、ｒａｓｐ２１及ｐ５３可能与大肠病的发生有关，三者在大肠病的发生中可能起协同作用。     

肝细胞癌及癌旁肝组织中bcl—2和p53蛋白表达与？…

目的：探讨ｂｃｌ－２和ｐ５３蛋白的表达与端粒酶活性的相关性及其与ＨＣＣ发生的关系。方法：利用端粒酶原位标记法显示端粒酶活性,采用Ｓ－Ｐ法免疫组化技术的检测ｂｃｌ－２和ｐ５３蛋白。结果：端粒酶在ＨＣＣ中的阳性率（９１．７％）显著高于癌旁肝组织（５８．３％）（Ｐ〈０．０５）,端粒酶活性强度与ＨＣＣ分化程度无关（Ｐ〉０．０５）;癌组织中ｂｃｌ－２和ｐ５３蛋白的阳性率均高于癌旁组织（Ｐ〈０．０１）;ＨＣＣ     

p53,c—erbB—2,PCNA和EGFR在膀胱癌中过表达及 …

目的：研究癌基因和抑癌基因蛋白产物在膀胱移行细胞癌中异常表达与病理分级、临床分期、复发和预后的关系。方法：应用免疫组化Ｓ－Ｐ法检查１１７例膀胱移行细胞癌组织中ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ的表达水平。结果：１１７例膀胱移行细胞癌中ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ阳性表达率分别为４７．０％、２９．９％、５３．８％和４８．７％。ｐ５３和ＰＣＮＡ阳性表达产物定位于肿瘤细胞核内，     

乳腺导管原位癌病理形态及c-erbB-2、p53和PCNA表达

目的：对乳腺导管原位癌进行病理形态分析，并行ｃ－ｅｒｂＢ－２、ｐ５３癌基因蛋白、增殖细胞核抗原（ＰＣＮＡ）表达以及相关性的研究，以期为临床判断潜在恶性程度及预后提供参考指标。方法：运用病理形态分析以及枸橼酸－微波－ＡＢＣ免疫组化法对２５例常规福尔马林固定、石蜡包埋乳腺导管原位癌组织进行回顾性研究。结果：（１）２５例乳腺原位导管癌ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ表达的阳性率分别为３６．０％，４０．０％和４０．０％；（２）粉刺型ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ表达的阳性率均高于非粉刺型，而且ｃ－ｅｒｂＢ－２阳性率相差有显著性（Ｐ＜０．０５）；（３）坏死、核异型性、核分裂数与ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ的表达有关，其中，坏死与ＰＣＮＡ阳性表达显著相关（Ｐ＜０．０５），核异型性与ｃ－ｅｒｂＢ－２蛋白表达显著相关（Ｐ＜０．０５）。结论：乳腺导管原位癌无论病理形态还是生物学行为都是异质性的，除了组织学亚型，某些形态指标以及ｃ－ｅｒｂＢ－２癌基因蛋白的表达也可作为恶性度指标。     

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     

癌基因c—erbB—2,抗癌基因P53在乳腺癌中表达的临床病理研究

应用ＡＢＣ法、ＬＳＡＢＩ地对１４４例乳腺癌及癌旁组织进行了ｃ－ｅｒｂＢ－２，ｐ５３基因蛋白表达的研究。结果，ｃ－ｅｒｂＢ－２表达阳性率为４８．６％，浸润性导管是性率最高（７４．１％），其表达与肿瘤体积、淋巴结转移、组织分级、核分裂计数、临床分期呈正相关，与雌激素受体（ＥＲ）、孕激素受体（ＰＲ）状况呈负相关，表达者 ５年生存率显著低于表达阴性者，因而ｃ－ｅｒｂＢ－２表达的检测可作为评估乳腺癌预后的有     

cyclinD1、p16、Rb在胸腺瘤中表达及预后意义

目的：探讨ｃｙｃｌｉｎ Ｄ１、ｐ１６、Ｒｂ蛋白在胸腺瘤中表达及预后意义。方法；应用免疫组化Ｓ－Ｐ法，对５４例胸腺瘤标本进行检测。结果：ｃｙｃｌｉｎＤ１、ｐ１６，Ｒｂ蛋白在髓质型，混合型胸腺瘤中阳性表达率分别为２３．１％（３／１３）、６９．２％（９／１３），５３．９％（７／１３），器官样，普通皮质型胸腺瘤中阳性表达率分别为５０．０％（８／１６）、７５．０％（１２／１６）、７５．０％（１２／１６），高     

p53、c-erbB-2、PCNA和EGFR在膀胱癌中过表达及其意义

目的：研究癌基因和抑癌基因蛋白产物在膀胱移行细胞癌中异常表达与病理分级、临床分期、复发和预后的关系。方法：应用免疫组化Ｓ－Ｐ法检查１１７例膀胱移行细胞癌组织中ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ的表达水平。结果：１１７例膀胱移行细胞癌中ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ阳性表达率分别为４７．０％、２９．９％、５３．８％和４８．７％。ｐ５３和ＰＣＮＡ阳性表达产物定位于肿瘤细胞核内，ｃ－ｅｒｂＢ－２阳性表达产物定位于细胞膜上，ＥＧＦＲ阳性表达产物定位于细胞膜或细胞浆内。结果表明ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ异常表达与膀胱癌的分级、分期、复发及术后生存率等之间有统计学意义。结论：ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ异常表达有助于评估膀胱癌预后，多基因异常表达作为预后评价指标更有意义。     

癌基因c─erbB─2、抗癌基因p53在乳腺癌中表达的临床病理研究

应用ＡＢＣ法、ＬＳＡＢ法对１４４例乳腺癌及癌旁组织进行了ｃ─ｅｒｂＢ─２、ｐ５３基因蛋白表达的研究。结果：ｃ─ｅｒｂＢ─２表达阳性率为４８．６％，浸润性导管癌阳性率最高（７４．１％）；其表达与肿瘤体积、淋巴结转移、组织分级、核分裂计数、临床分期呈正相关，与雌激素受体（ＥＲ）、孕激素受体（ＰＲ）状况呈负相关，表达者５年生存率显著低于表达阴性者．因而ｃ─ｅｒｂＢ─２表达的检测可作为评估乳腺癌预后的有力指标。ｐ５３表达的阳性率为２４．７％，髓样癌阳性率较高（３８．５％）；ｐ５３表达与组织分级和淋巴结转移状况呈正相关；阳性率随肿瘤体积增大和临床分期升高而增加；在ＥＲ或ＰＲ阴性者中ｐ５３阳性率高于ＥＲ或ＰＲ阳性者。本文未发现ｃ─ｅｒｂＢ─２与ｐ５３表达的相关性；两者表达均阳性者与仅一种阳性者在肿瘤体积、淋巴结转移和临床分期方面差异无显著性。     

膀胱移行细胞癌中p16、p53及c-erbB-2蛋白的异常表达及临床意义

目的研究膀胱癌组织中p16、p53及c-erbB-2蛋白表达,探讨其与膀胱癌病理分级、临床分期和转移的关系.方法应用免疫组化SP法对75例膀胱癌组织中p16、p53及c-erbB-2蛋白表达进行检测.结果75例膀胱癌中p16、p53及cerbB-2的阳性率分别为41.3%(31/75)、44%(33/75)和40%(30/75),p16、和c-erbB-2基因在膀胱癌中的阳性率与肿瘤病理分级和临床分期有显著性统计学意义(P＜0.05),p53及c-erbB-2阳性率与肿瘤临床分期及转移有密切的关系(P＜0.01).773%(58/75)肿瘤有上述癌基因和(或)抑癌基因的异常表达,其中53.3%(40/75)的肿瘤同时有多个基因的表达异常.结论肿瘤的多基因分析比单基因分析更有价值,癌基因c-erbB-2和抑癌基因p16、p53基因的表达异常及协同作用在膀胱癌的发生发展中起重要作用.     

膀胱移行细胞癌中c-erbB-2、p53及p16 蛋白的表达

目的　探讨膀胱癌组织中p16、c erbB 2和p5 3蛋白表达与膀胱癌病理分级、临床分期和转移的关系。方法　应用免疫组化SP法对 75例膀胱癌组织中p16、p5 3及c erbB 2蛋白表达进行检测。结果　 75例膀胱癌中p16、p5 3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蛋白在膀胱癌中的阳性率与肿瘤病理分级和临床分期有显著意义 (P<0 0 5 ) ,p5 3和c erbB 2阳性率与肿瘤临床分期及转移有密切的关系 (P <0 .0 1)。 77.3% (5 8 75 )肿瘤有上述蛋白的阳性表达 ,其中 5 3.3% (40 75 )的肿瘤同时有多个蛋白的阳性表达。结论　肿瘤的多因素分析比单因素分析更有价值 ,癌基因c erbB 2和抑癌基因p5 3、p16蛋白的表达异常及协同作用在膀胱癌的发生发展中起重要作用     

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。     

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。     

癌基因MDM_2和抑癌基因p53在肉瘤组织中的变化及其相关性

目的：研究ＭＤＭ２癌基因和ｐ５３抑癌基因在人肉瘤发生中的作用。方法：应用分子杂交和免疫组化技术检测了５０例肉瘤组织、１３例良性间叶瘤和１０例癌组织中ＭＤＭ２及ｐ５３的分子改变。结果：ｐ５３过表达率在肉瘤为２４／５０（４８％）；ＭＤＭ２扩增和过表达在肉瘤为１９／４９（３８．８％）和２７／４９（５５％），而在良性间叶瘤分别为１／１３（７．７％）和１／１２（８．３％），癌组均为１／１０（１０％）；ＭＤＭ２基因的异常在不同类型肉瘤间存在差异性；ＭＤＭ２扩增和过表达间存在不一致性：１９例扩增中１６例有过表达，而１１例过表达者无基因扩增。两基因改变的相关分析发现，２４例ｐ５３阳性中１８例有ＭＤＭ２改变。结论：ＭＤＭ２癌基因异常与间叶性肿瘤的恶性表型高度相关，并有一定类型特异性；ＭＤＭ２与ｐ５３的改变在肉瘤的发生中密切相关     

rasp21、c-erbB-2、c-erbB-3、p53、nm23蛋白与细支气管肺泡癌淋巴结转移的关系

目的：研究rasp21、c-erbB-2、c-erbB-3、p53、nm23蛋白与细支气管肺泡癌（BAC）淋巴结转移的关系。方法：应用免疫组化LSAB法检测50例BAC（其中18例伴淋巴结转移）标本。结果：rasP21、c－erbB－2、c－erbB3、P53蛋白在伴或不伴淋巴结转移的BAC中的表达差异无显著性（P＞0．05）。但在18例伴淋巴结转移的BAC原发灶内,rasP21、c－erbB-2、c－erbB-3、p53中两种及两种以上同时表达的有4例（22％）,而在相应的淋巴结转移灶中则为8例（44％）。nm23／NDPK在BAC中的表达（34／50,78％）高于癌旁肺实质（P＜0．01）。在伴淋巴结转移的BAC中nm23／NDPK表达率为56％（10／18）,在无淋巴结转移的BAC中为91％（29／32）,差别有高度显著性（P＜0．01）O结论：肿瘤转移受多种基因及其表达产物的调控。nm23基因的表达不仅与BAC的发生有关,而且在BAC中起到转移抑制基因的作用。     

PROGNOSTIC SIGNIFICANCE OF THE CO-EXPRESSION OF p53 AND c-erbB-2 PROTEINS IN BREAST CANCER

The immunohistochemical expression of p53 and c-erbB-2 gene proteins was examined in a series of 130 breast adenocarcinomas. This study intended to investigate whether the frequency of the altered expression of the tumour suppressor gene p53 and the overexpression of the oncogene c-erbB-2 in breast cancer tissue cells correlated with other variables known to affect the biological behaviour of these tumours and the overall survival of the patients (median follow-up time: 6 years). The expression of p53 protein and c-erbB-2 gene product was evaluated immunohistochemically. Expression of p53 protein was detected in 30 (23 per cent) of the neoplasms examined, while 26 (20 per cent) out of the 130 cases demonstrated positive c-erbB-2 immunoreactivity. There was a statistically significant association between p53 protein expression and primary tumour size, lymph node involvement, and oestrogen receptor positivity. The incidence of c-erbB-2 positivity was significantly correlated with high tumour grade, axillary node invasion, large tumour size, and the absence of steroid receptors. p53 immuno-expression was clearly associated with c-erbB-2 protein overexpression. Concomitant p53 and c-erbB-2 positive immunolabelling, which emerged in 14 out of the 130 cases (10·7 per cent), was clearly associated with high grade, large size, positive nodal status, ductal infiltrating (NOS) histological type, and low values of progesterone receptors. Overall survival of patients was not significantly related to the immunoreactivity of either p53 or c-erbB-2 considered separately, whereas there was a clearly significant trend to worse overall prognosis in cancers with double p53/c-erbB-2 positive phenotype. The simultaneous immunodetection of p53/c-erbB-2 appears to have greater negative prognostic relevance than their separate expression.     

The prognostic significance of c-erbB-2 and p53 protein expressions in gastric carcinoma--a multivariate analysis of prognostic factors.

152 curative gastrectomy specimens from patients with gastric carcinoma were examined in an attempt to assess the prognostic value of c-erbB-2 and mutant p53 protein expressions. The labeled streptavidin-biotin method was applied to routinely fixed and paraffin-embedded tissue sections, using the polyclonal and monoclonal antibodies against the c-erbB-2 protein and the mutant form p53 protein, respectively. In this examination, staining of c-erbB-2 protein was found in 9.2% of these carcinomas. The c-erbB-2 stained tumors were significantly associated with the tumors whose diameters were smaller than 5cm, and were more likely to be associated with serosal invasion and nodal involvement than the unstained ones. However, there was little association between staining of c-erbB-2 protein and clinicopathologic findings such as age, sex, location, histology, gross type, lymph node status, depth of invasion, and stage. The survival analysis of 104 patients with stage III gastric carcinoma revealed no significant association between c-erbB-2 staining status and survival duration. The 5-year survival rates of the c-erbB-2 positive group and its negative group were 21% and 28%, respectively. Positive p53 protein expression was observed in 46% of 152 carcinomas. There was no significant association between p53 expression and parameters such as age, sex, location, histology, gross type, and size. The p53 stained tumors were more likely to be associated with lymph node metastasis, serosal invasion than p53 unstained ones; but this did not reach significance. The 5-year survival rates of the p53 positive group and counter part group were 27% and 31%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The correlation between expression of oncogene protein products p53, p21, p185 and cell differentiation and prognosis in rhabdomyosarcoma

OBJECTIVE: To study the correlation between expression of oncogene protein products p53, P21, p185 and histological type, cell differentiation and prognosis in rhabdomyosarcoma (RMS). METHODS: 41 RMS cases which had follow-up material were selected for this study. Expression of protein products of oncogene p53, p21 and p185 were synchronously detected and compared by immunohistochemical ABC method. RESULTS: The positive rates for p53, p21 ras and P185 c-erbB-2 were 72%, 68% and 60% respectively. Positive expression did not relate to age, sex or RMS histological type, but related to the degree of RMS differentiation. The positive rate of p53 ad p21 ras in well differentiated cases were 42.9% and 28.6% while that of the poorly differentiated group was 85% and 80% respectively (P < 0.05). The psoitive rate of p53 in the RMS group with metastasis was 86.6%, significantly higher than that of the non-metastasized group, which was 66.7% (P < 0.05). There was a significant difference between those with one year survival, whose p52 positive rate was 86.7% and those who survived for more than 3 years, whose p53 positive rate was 47.1% (P < 0.05). CONCLUSION: The results suggest that the irregular expressions of p53 and p21 were related to tumor differentiation and the degree of malignancy. p53 positivity may indicate a poor prognosis.