胃肠道平滑肌肿瘤ras p21及DNA与预后的关系

作者应用细胞免疫荧光染色技术及流式细胞术对５５例胃肠道平滑肌肿瘤石蜡包埋标本的ｒａｓｐ２１表达及ＤＮＡ含量同时进行定量分析。结果：１４例平滑肌瘤均为二倍体和ｒａｓｐ２１低表达；１２例潜在恶性平滑肌肿瘤出现４例异倍体（３３％），９例ｒａｓｐ２１过度表达（７５％），并且大多数出现在该组的二倍体肿瘤中；２９例平滑肌肉瘤全部为异倍体（１００％）（Ｐ＜０．００５），而ｒａｓｐ２１过度表达率未见继续增高（７２％）（Ｐ＜０．００５）。３３例异倍体肿瘤的ｒａｓｐ２１过度表达率（７３％）明显高于２２例二倍体肿瘤（２７％）（Ｐ＜０．００５）。ｒａｓｐ２１低表达的二倍体肿瘤预后最好，ｒａｓｐ２１过度表达的异倍体肿瘤预后最差（Ｐ＜０．００５）。作者认为，ＤＮＡ异倍体及ｒａｓｐ２１过度表达均是恶性肿瘤的标志；ｒａｓｐ２１过度表达主要出现在恶性肿瘤的早期，并且持续稳定的表达；ｒａｓｐ２１表达和ＤＮＡ含量可以互补作为判断胃肠道平滑肌肿瘤患者预后的客观指标。     

ras、p53基因突变和蛋白表达与尿路上皮肿瘤预后的关系

目的　研究ｒａｓ、ｐ５３ 基因突变和蛋白表达及ＤＮＡ 倍体异常与尿路上皮肿瘤预后关系。　方法　应用ＰＣＲＳＳＣＰ和流式免疫荧光法检测５２ 例尿路上皮肿瘤Ｋｒａｓ 和ｐ５３ 基因突变及蛋白表达和ＤＮＡ 含量变化。　结果　Ｋｒａｓ、ｐ５３ 基因突变分别为５ 例（９ ．６ ％ ） 和２２ 例（４２ ．３ ％ ） ;ｒａｓ ｐ２１ 、ｐ５３ 蛋白阳性表达分别为３６ 例（６９ ．２ ％ ） 和３３ 例（６３ ．５ ％ ） ;异倍体和二倍体肿瘤分别为２２ 例（４２ ．３ ％ ） 和３０ 例（５７ ．７ ％ ） ;ＤＮＡ 倍体异常、ｐ５３ 基因突变及ｒａｓ ｐ２１ 和ｐ５３ 蛋白表达与肿瘤病理分级、分期及预后密切相关（ Ｐ＜ ０ ．０１） ;异倍体肿瘤其ｐ５３ 基因突变、ｒａｓ ｐ２１ 和ｐ５３ 蛋白表达率均明显高于二倍体肿瘤（ Ｐ＜ ０ ．０１） 。　结论　ＤＮＡ 倍体异常、ｐ５３ 基因突变及ｒａｓ ｐ２１ 和ｐ５３ 蛋白表达对尿路上皮肿瘤预后判断有重要意义。     

结直肠癌p21ras的计量分析与预后

应用ｒａｓ癌基因产物ｐ２１￣ｒａｓ免疫组化染色的图象分析技术、流式细胞分析技术分别测定８３例结直肠癌的ｐ２１￣ｒａｓ平均光密度值（ｐ２１Ｄ）和ＤＮＡ指数（ＤＩ），结合临床随访和病理学资料探讨其预后价值。结果提示：结直肠癌的ｐ２１Ｄ明显高于正常粘膜（Ｐ＜０．００１），术后生存≥５年组的ｐ２１Ｄ明显低于＜５年组（Ｐ＜０．００１）。高ｐ２１Ｄ组患者预后较低ｐ２１Ｄ组差。二倍体肿瘤及低ｐ２１Ｄ异倍体肿瘤患者预后较高异倍体肿瘤患者明显好。Ｄｕｋｅｓ′ｃ期的ｐ２１Ｄ高于Ｂ和Ａ期。表明ｒａｓ癌基因表达与结直肠癌病程进展及转归有关，测定结直肠癌的ｐ２１￣ｒａｓ的表达和ＤＮＡ倍体将有助于预后判断。     

rasp21和p53基因蛋白在乳腺癌和乳腺良性病变细胞表达的定量研究

ｒａｓｐ２１和ｐ５３基因蛋白在乳腺癌和乳腺良性病变细胞表达的定量研究左连富，齐风英，胡俊兰，郭建文，刘江惠本文应用流式免疫分析技术对乳腺良性病变和癌细胞ｐ２１蛋白和ｐ５３蛋白表达进行定量研究，探讨其与病理学分级、ＤＮＡ倍体和预后的关系。１．材料和方法...     

p21 ras和nm23-H1表达与胃癌淋巴结转移的关系

为探讨ｐ２１ｒａｓ和ｎｍ２３－Ｈ１表达与胃癌淋巴结转移的关系,采用ＬＳＡＢ法观察了８０例胃癌患者的ｐ２１ｒａｓ和ｎｍ２３Ｈ１的表达,并分析其与淋巴结转移的关系,结果：有淋巴结转移（ＬＮＭ）组ｐ２１ｒａｓ表达阳性率（６２．５％）明显高于无ＬＮＭ组（４２．５％）但ｎｍ２３－Ｈ１表达阳性率（２７．５％）则明显低于无ＬＮＭ组（４７．５％）ＬＮＭ数为１－３枚和ｐ２１ｒａｓ表达阳性率（３３．３％）明显低于４－     

影响胰腺癌预后的因素分析

目的　探讨影响胰腺癌预后的决定因素。 方法　应用流式细胞仪检测胰腺癌ＤＮＡ倍体６２ 例,采用免疫组织化学法检测ｐ２１ 、ｐ５３ 在胰腺癌中的表达,应用Ｃｏｘ 比例风险模型对其预后因素进行分析。 结果　本组共有６２ 例经手术和病理学检查证实的胰腺癌病人,其中胰腺癌患者二倍体２５ 例,四倍体１１ 例,预后较好,平均生存期分别为２８ 个月和３０ 个月,非四倍体异倍体者２６ 例平均生存期仅为５ 个月。胰腺癌组织ｐ２１ 阳性率为８９％ ,ｐ５３ 阳性率为５１％ 。二者表达均与临床分期密切相关;单因素分析发现,ＤＮＡ倍体、后腹膜浸润、手术方式、肝转移、临床分期、ｐ２１ 表达、十二指肠浸润等与预后密切相关,多因素分析中仅ＤＮＡ倍体和临床分期是独立预后决定因素。 结论　ＤＮＡ倍体和临床分期是胰腺癌独立预后的决定因素     

直肠癌旁移行粘膜p53、p21表达及其临床意义

目的 探讨直肠癌移行粘膜的生物病理学性质。方法 应用组织化学和免疫组织化学方法观察，３４例直肠癌旁粘膜中ｐ５３，ｐ２１蛋白表达及其与粘蛋白改变的关系。结果 ２９．４％（１０／３４）直肠癌旁移行粘膜体杯状细胞胞浆内顾在ｐ５３表达，其范围不超出远端４ｃｍ肠管，ｐ２１在２６．５％（９／３４），癌旁移行粘膜腺体柱六细胞头内存在表达，其范围不超过２ｃｍ肠管。结论 直肠癌移行粘膜中存在ｐ５３失活及ｒａｓ激活，系     

ras和p53在甲状腺癌中的表达

目的 探讨ｒａｓ和ｐ５３基因过度表达在甲状腺癌发生中的相互作用,以及甲状腺癌的临床病理标准与ｒａｓ和ｐ５３基因过度表达的关系。方法 采用ＬＳＡＢ免疫组化法检测了ｒａｓ和ｐ５３在８０例甲状腺病变中的表达,其中５４例为甲状腺癌,２６例为良性甲状腺结节性病变。结果 ｒａｓ和ｐ５３在甲状腺癌和良性甲状腺结节性病变中的表达阳性率分别为９０．７％及２３．０％和５５．５％及３０．７％,两者相比较,差异有显著性意     

反义N－rasl DNA片段对人膀胱癌BIU－87细胞系作用的研究

将载有反义人Ｎ－ｒａｓｌ（ｅｘｏｎｌ）ＤＮＡ片段的重组表达质粒ｆＰＧＶ１－ＭＴ－Ｎｒａｓｌ（Ａ）导入人膀胱移行细胞癌ＢＩＵ－８７细胞系，可以导致ＢＩＵ－８７细胞恶性行为的部分改变，表现在生长速度减慢２１．７％～６５．６％，３Ｈ－ＴｄＲ掺入降低４５．８％，软琼脂克隆形成能力下降４８．３％，同时，Ｎ－ｒａｓ－ｍＲＮＡ及Ｐ２１ｒａｓ表达减少。     

反义N—rasl DNA片段对人膀胱癌BIU—87细胞系作用的研究

将载有反义人Ｎ－ｒａｓｌ（ｅｘｏｎｌ）ＤＮＡ片段的重组表达质粒ｆＰＧＶ１－ＭＴ－Ｎｒａｓｌ（Ａ）导入人膀胱移行细胞癌ＢＩＵ－８７细胞系，可以导致ＢＩＵ－８７细胞恶性行为的部分改变，表现在生长速度减慢２１．７％～６５．６％，＾３Ｈ－ＴｄＲ掺入降低４５．８％，软琼脂克隆形成能力下降４８．３％，同时，Ｎ－ｒａｓ－ｍＲＮＡ３及Ｐ２１ｒａｓ表达减少。     

ras突变和rasP21蛋白表达与尿路上皮肿瘤预后关系

应用聚合酶链式反应加单链多态性分析(PCR-SSCP)及流式细胞木和细胞免疫荧光技术检测52倒尿路上皮肿瘤K-ras基因突变及rasP21蛋白表达和DNA含量变化,研究ras突变和rasP21蛋白表达及DNA倍体异常与尿路上皮肿瘤预后关系。K-ras基因突变5例(9.65),rasP21蛋白阳性表达36例(69.2％);异倍体22例(42.3％),二倍体30例(57.7％);DNA倍体异常和rasP21蛋白表达随肿瘤病理分级和分期的上升而增加,与肿瘤预后呈正相关(P<0.01);异倍体肿瘤其rasP21蛋白表达率明显高于二倍体肿瘤(P<0.01)。DNA倍体异常和rasP21蛋白表达对尿路上皮肿瘤预后有预测意义。     

Ras gene activation and epidermal growth factor receptor expression in human colon cancer

The expression of various epitopes of epidermal growth factor receptor (EGFr) and mutational activations of ras gene product p21 in colorectal primary cancers from 16 patients have been analyzed in this study. Eight noncancerous colons were used as controls. Indirect immunoperoxidase staining was performed using Avidin-Biotin Complex assay. Monoclonal antibodies against carbohydrate and polypeptide epitopes of EGFr and monoclonal antibodies against "wild-type" and "mutant" ras p21 were used as specific probes. There was no specific expression of the polypeptide epitope of EGFr observed in any of the colon cancers or normal colon tissues. Four of the sixteen tumors (25%) expressed the carbohydrate epitope of EGFr. Glycine----arginine mutation and glycine----valine mutation of codon 12 in ras p21 was observed in 40 and 31% of colon cancers, respectively. Although normal colon showed expression of wild-type ras in about half the cases studied, there was no mutational activation of the ras genes. The morphologically adjacent normal colon mucosa in cancer patients expressed varying levels of mutational activation involving the codon 12. The presence of unusual carbohydrates relating to the EGFr and the products of ras gene activation by point mutations in colon cancers may imply a functional role in transformation.     

ras和p53基因在原发性胆囊癌早期诊断中的应用研究

目的 研究p53和ras基因在原发性胆囊癌早期诊断中的应用价值。方法 用免疫组化的方法分别检测炎症组、增生组、非典型增生组、癌变组的胆囊黏膜P53和P21蛋白的阳性表达。结果 P53蛋白在非典型增生组开始表达，与癌变组的阳性表达率无显著性差异；P21蛋白在癌变组高表达，炎症组低表达，两组间有显著性差异；两种蛋白的阳性强度随病变的恶性程度逐渐增加。结论 p53和ras基因在胆囊癌早期诊断方面有较高的应用价值。     

结直肠癌中P53和Kras基因突变与血管内皮生长因子表达的关系

目的探讨结直肠癌中P53和K-ras基因突变与血管内皮生长因子(VEGF)的关系。方法采用RT-PCR技术和聚合酶链式反应-单链构像多态性分析(PCR-SSCP)方法,对46例结直肠癌的新鲜癌组织进行P53、K-ras基因突变率和VEGF表达率的检测。结果46例结直肠癌中VEGF表达阳性率为52.2%(24/46),P53基因突变率为63.0%(29/46),K-ras基因突变率为43.4%(20/46)。P53基因突变的29例中VEGF表达阳性20例,占68.9%,表达阴性9例,占31.0%,P<0.05。K-ras基因突变的20例中VEGF表达阳性14例,占70.0%,表达阴性6例,占30%,P<0.05。结论结直肠癌组织中P53基因突变和K-ras基因突变与VEGF表达呈正相关,此点为临床基因治疗肿瘤提供了重要理论依据。     

人乳头瘤病毒DNA相关序列与p53基因突变对大肠癌生物学行为的影响50例报告

目的探讨人乳头瘤病毒（ＨＰＶ）ＤＮＡ相关序列与ｐ５３基因突变及ｐ５３蛋白表达的关系及其对大肠癌生物学行为的影响。方法采用ＰＣＲ方法检测大肠癌及癌旁组织、肝转移灶中ＨＰＶＤＮＡ相关序列。并应用ＰＣＲＳＳＣＰ及免疫组化技术分别检测ｐ５３基因突变及ｐ５３蛋白表达。结果在５０例大肠癌中,检出ＨＰＶ１６、１８ＤＮＡ相关序列２６例（５２０％）,其中ＨＰＶ１６ＤＮＡ４例（８０％）,ＨＰＶ１８ＤＮＡ２２例（４４０％）。ｐ５３基因突变率为５６０％。ｐ５３蛋白表达阳性率为４２０％。ＨＰＶＤＮＡ相关序列与ｐ５３基因突变及ｐ５３蛋白表达呈正比关系。结论ＨＰＶＤＮＡ相关序列可促进细胞转化、致ｐ５３基因突变、抑制细胞的凋亡,与大肠癌的发生发展有密切关系。     

Expression of ras p21 oncogene product on human bladder tumors

The immunohistochemical localization of ras p21 oncogene product was examined in human bladder cancer. These bladder cancers consist of 52 superficial bladder tumors and 10 cases of invasive tumor. Five (9.6%) of 52 superficial tumors were demonstrated to be positive for ras p21 product. Two (20%) of 10 cases which showed deep tumor infiltration were demonstrated to be positive for ras p21 oncogene product. When we analyzed the incidence of positive staining for ras p21 with regard to histological grade of bladder cancer, 2 of 30 (7%) patients with G1, 4 of 26 (15%) with G2, and 1 of 6 (17%) with G3 had positive staining for the ras p21 oncogene product. One of five patients who showed positive staining on tumors had tumor recurrence 3 months later. The remaining 4 patients positive for the ras p21 oncogene product had no tendency for recurrence in 11-19 months' follow-up. Therefore, the incidence of detection of ras p21 oncogene product on superficial and deep infiltrating bladder tumor was similar and there was no significant correlation between the incidence of positive ras p21 staining and depth of invasion of bladder tumors or histological grade.     

DNA ploidy,c-myc oncoprotein p62 and v-H-ras oncoprotein p21 in colorectal carcinoma

DNA ploidy and expression of the c-myc oncoprotein p62 and the v-H-ras oncoprotein p21 were examined in 54 colorectal carcinomas. DNA ploidy, determined by DNA flow cytometry, was diploid in 19 samples and aneuploid in 35. Expression of the p62 oncoprotein, determined by immunohistochemical staining, was intensely positive in 18 samples while that of the p21 oncoprotein, also determined by immunohistochemical staining, was positive in 29. There was no correlation between DNA ploidy and expression of the p62 oncoprotein, and DNA ploidy did not correlate with expression of the p21 oncoprotein. There was, however, a close correlation between expression of the p62 oncoprotein and that of the p21 oncoprotein being P<0.01 according to Peason's chisquare test.     

Comparison of microsatellite instability and chromosomal instability in predicting survival of patients with T3N0 colorectal cancer

BACKGROUND: At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal instability, are implicated in colorectal tumorigenesis. Their respective roles in predicting clinical outcomes of patients with T3N0 colorectal cancer remain unknown. METHODS: Eighty-eight patients with a sporadic T3N0 colon or rectal adenocarcinoma were followed up for a median of 67 months. For chromosomal instability analysis, Ki-ras mutations were determined by single-strand polymerase chain reaction, and p53 protein staining was studied by immunohistochemistry. For MSI analysis, DNA was amplified by polymerase chain reaction at 7 microsatellite targets (BAT25, BAT26, D17S250, D2S123, D5S346, transforming growth factor receptor II, and BAX). RESULTS: Overall 5-year survival rate was 72%. p53 protein nuclear staining was detected in 39 patients (44%), and MSI was detected in 21 patients (24%). MSI correlated with proximal location (P <.001) and mucinous content (P <.001). In a multivariate analysis, p53 protein expression carried a significant risk of death (relative risk = 4.0, 95% CI = 1.6 to 10.1, P =.004). By comparison, MSI was not a statistically significant prognostic factor for survival in this group (relative risk = 2.2, 95% CI = 0.6 to 7.3, P =.21). CONCLUSIONS: p53 protein overexpression provides better prognostic discrimination than MSI in predicting survival of patients with T3N0 colorectal cancer. Although MSI is associated with specific clinicopathologic parameters, it did not predict overall survival in this group. Assessment of p53 protein expression by immunocytochemistry provides a simple means to identify a subset of T3N0 patients with a 4-times increased risk for death.