卵巢癌p^53基因248,249位密码子点突变的研究

卵巢癌ｐ５３基因２４８、２４９位密码子点突变的研究姚桂梅康志海李佩玲刘海燕胡双玖应用聚合酶链反应－限制性片段长度多态性方法（ＰＣＲ－ＲＦＬＲ），分析卵巢恶性肿瘤中ｐ５３基因第２４７／２４８、２４９／２５０、ＭｓｐＩ、ＨａｅⅢ酶切位点的突变情况，探讨其...     

P53基因在卵巢癌中的研究进展

Ｐ５３基因是一种肿瘤抑制基因，位于人的染色体１７Ｐ１３．１，编码３９３个氨基酸组成的核磷酸蛋白，参与细胞的生长调控和ＤＮＡ的修复过程，Ｐ５３基因点突变频率为２９％－７９％。点突变的位点较集中在５、６、７、８外显子，但在卵巢癌中并未发现Ｐ５３基因的突变“热点”。     

妇科肿瘤p53基因突变及临床意义初步探讨

检测妇科肿瘤Ｐ５３基因第５－８外显子的突变并探讨其临床意义。方法用聚合酶链反应－单链构象多态性分析银染技术,检测了１４８例子宫平滑肌瘤１６例子宫内膜癌,１５例宫颈癌、１７例卵巢癌的新鲜肿瘤组织Ｐ５３期第５－８外显子的突变。结论人子宫平滑肌瘤存在Ｐ５３基因突变,但不是子宫平滑肌瘤的特征改变。     

p53抑癌基因与卵巢癌

ｐ５３抑癌基因与卵巢癌李广大，焦书竹抑癌基因，又称肿瘤抑制基因、隐性癌基因和肿瘤易感基因。现代分子生物学研究表明，肿瘤发生是正常细胞基因组多重损伤的过程。在此过程中，既可出现原癌基因，即细胞癌基因的激活，也可出现抗癌基因的缺失和失活，从而引起细胞生长...     

p53基因与白细胞介素6对卵巢癌生物学行为的影响

卵巢癌死亡率居女性生殖系统恶性肿瘤之首，恶性肿瘤的生长与转移，往往是患者死亡的直接原因，也是恶性肿瘤研究中最重要的问题。基础研究证明，癌基因的过度表达、抑癌基因的失活及细胞生长因子调节的异常，是患者体内正常组织癌变并导致其生物学行为一系列改变的基本原...     

野生型p53基因cDNA转染对卵巢癌细胞系SKOV—3生物学行为的…

目的：研究野生型ｐ５３基因ｃＤＮＡ转染对卵巢癌细胞系ＳＫＯＶ－３生物学行为的影响，方法：用脂质体介导的转染技术，将含有全长人野生型ｐ５３ｃＤＮＡ的真核重组质粒和空载体质粒，分别导入不表达ｐ５３的ＳＫＯＶ－３细胞，观察细胞生物学行为的改变。结果；（１）共获２个ｐ５３ｃＤＮＡ转染克隆（ｐＣ５３）和２个空载体转染克隆（ｐＮｅｏ）；（２）ｐＣ５３和ｐＮｅｏ细胞形态学与ＳＫＯＶ－３无显著差别，（３）ｐＣ５３     

卵巢上皮性癌p53基因突变的检测和序列分析

目的了解卵巢上皮性癌ｐ５３基因突变的特点及其与临床分期的关系。方法采用聚合酶链反应－单链构象多态性检测（ＰＣＲ－ＳＳＣＰ）和序列分析的方法对４６例卵巢上皮性癌进行外显子５、６、７突变的检测和分析。结果ｐ５３基因突变８例并得到证实。包括８个点突变（６个错义突变,１个静息突变和１个内含子突变）和１个碱基对插入突变（在下游产生终止信号）。突变中碱基转换突变占总突变的８８．９％（８／９）,并以Ｇ→Ａ的转换突变为主,占转换突变的８７．５％（７／８）。１７５、２４５位密码子的突变占总突变的６２．５％。临床Ⅰ、Ⅱ期的突变率为２０．０％,临床Ⅲ、Ⅳ期为１６．７％,差异无显著性（Ｐ＞０．０５）。结论卵巢上皮性癌ｐ５３基因突变是自发性突变,是由于ＤＮＡ合成和修复过程中的随机错误所致。１７５与２４５位密码子可能是卵巢上皮性癌ｐ５３基因突变的主要位点。ｐ５３基因突变与临床分期无关,故认为ｐ５３基因突变于卵巢癌早期就有所发生,并持续于肿瘤发展的全过程。     

野生型p53基因对人卵巢癌细胞株的生长抑制作用

目的：探讨野生型ｐ５３(ｗｔ ｐ５３)基因对人卵巢癌细胞株的生长抑制作用。方法：利用脂质体介导,将含有人全长ｗｔ－ｐ５３基因ｃＤＮＡ的真核表达载体质粒ｐＣＥＰ４／ｐ５３和空载体质粒ｐＣＥＰ４分别转染卵巢癌ＳＫＯＶ３细胞株,分别命名为ＳＫＯＶ３－ｐＣＥＰ４／ｐ５３细胞(C组)、ＳＫＯＶ３－ｐＣＥＰ４细胞(B组),另设ＳＫＯＶ３细胞为正常对照组（Ａ组）。观察细胞体外生长情况和凋亡变化。结果：外源性ｐ５３基因在Ｃ组细胞中获表达,细胞生长曲线显示ｐ５３的导入使ＳＫＯＶ３细胞生长受到明显抑制,Ｃ组平均细胞集落数（１８．６±１．８个）少于Ａ组（２４．３±２．２个）和Ｂ组（２２．７±２．６）,差异有显著性（Ｐ（005）。ＭＴＴ法检测C组细胞活力明显低于Ａ、Ｂ组。Ｃ组细胞Ｇ０～Ｇ１期百分比（５７．７９％）及凋亡细胞百分比（13．９1％）均高于Ｂ组（４６．０２％、２．０８％）和Ａ组（４３．６２％、０）。结论：ｗｔ－ｐ５３基因可介导ＳＫＯＶ３细胞Ｇ１期停滞和细胞凋亡,抑制细胞体外生长。     

上皮性卵巢癌中p53蛋白表达与患者预后关系的探讨

上皮性卵巢癌中ｐ５３蛋白表达与患者预后关系的探讨荣风年１孙德刚１吴彩志１汤春生２（１山东省千佛山医院２山东省立医院）ｐ５３是临床上研究较早的一种抑癌基因，其对患者预后的意义尚有争论。虽有用ｐ５３作患者预后指标，结合治疗后患者的生存率曲线，研究ｐ５３蛋...     

抑癌基因p53在上皮性卵巢癌中的过度表达及临床意义

用免疫组织化学方法检测１１０例上皮性卵巢癌中抑癌基因ｐ５３蛋白的过度表达，以探讨其在上皮性卵巢癌发生及演进中的作用及其临床意义。结果显示：ｐ５３蛋白过度表达在上皮性卵巢癌中为５２．７％，而在正常及良性肿瘤中为阴性。不同期别卵巢癌中，ｐ５３蛋白过度表达阳性率不同，早期癌（Ｉ￣Ⅱ）中为２７．９％，晚期癌（Ⅲ￣Ⅳ）中为７０．６％，差异非常显著（Ｐ〈０．０１）。ｐ５３蛋白过度表达在不同分化程度的卵巢癌中的     

p53 Expression as a Prognostic Indicator of 5-Year Survival in Endometrial Cancer

BACKGROUND: One of the most common genetic alterations to occur in human cancers is an alteration of the p53 tumor suppressor gene. The purpose of this article was to build upon the authors' previous work with p53 and determine whether p53 was a prognostic indicator of 5-year survival. METHODS: One hundred thirty-seven consecutively surgically treated patients with endometrial cancer had their p53 expression studied by immunoperoxidase staining and quantified by image analysis. All patients were evaluable for 5-year survival. RESULTS: One hundred three patients had endometrioid adenocarcinoma; 6, adenosquamous carcinoma; 14, papillary serous carcinoma; 10, clear cell carcinoma; and 4, undifferentiated carcinoma. p53 expression ranged from 0.0 to 58.2% positive nuclear area with a mean of 11.5% (median 2.6%) for the cohort. For the patients with endometrioid carcinoma, the mean p53 expression was 7.1% while for the nonendometrioid tumors it was 24.6% (P<0.001). Fifty-nine of the 103 endometrioid tumors (57.3%) stained positive for p53 while 32 of the 34 nonendometrioid (94.1%) tumors stained positive (P<0.001). Increasing histologic grade correlated with an increasing p53 expression (P = 0.003). The percentage of tumors expressing p53 was found to be higher in FIGO stage II, III, and IV than in FIGO stage I cancer (P = 0.003). However, mean p53 expression did not differ between early (stage I) and advanced (stage II, III, and IV) cancers (P = 0.088). Utilizing 5-year survival as the endpoint for multivariate analysis, FIGO stage (P = 0.0028) and p53 expression (P<0.001) were the only independent prognostic indicators found. CONCLUSION: p53 expression is more commonly found in nonendometrioid than in endometrioid adenocarcinoma of the endometrium. It, along with FIGO stage, is an independent prognostic indicator of 5-year survival.     

子宫内膜癌p53抑癌基因蛋白表达及其与预后的关系

为研究抑癌基因ｐ５３与子宫内膜癌的关系，本研究用免疫组化ＡＢＣ法检测了２３例正常子宫内膜、４４例子宫内膜增殖症及１０３例子宫内膜癌组织中抑癌基因ｐ５３的表达情况。结果表明：突变型ｐ５３蛋白在于宫内膜癌组织中的阳性率为４７．６％，而在正常子宫内膜及各类型子官内膜增殖症中均为阴性。突变型ｐ５３的表达与子宫内膜癌的病理类型、组织分化、脉管浸润情况及ＤＮＡ异倍体等因素有关。ｐ５３表达阳性者的生存率明显低于无表达者，５年生存率分别为５９．９％及８３．４％。用Ｃｏｘ比例风险模型计算，结果表明ｐ５３表达阳性者的死亡危险度为阴性者的６．３４倍。突变型ｐ５３蛋白的出现与子宫内膜癌的恶性生物学行为有关。     

Phenotypic features with p53 alterations related to human papillomavirus and prognostic evaluation in cervical cancer

Cervical cancer is one of the most common tumor affecting women worldwide. Human papillomavirus (HPV) was found to have a causal relationship with cervical cancer and its precursors. The interaction between HPV E6 protein and p53 was identified in in vitro studies. The aim of the study was to evaluate the prevalence of p53 alterations related to HPV infection and the prognostic significance of p53 alterations in cervical cancer. Studies were identified by a MEDLINE search, and all relevant articles were retrieved from 1991 to March 2004. The prevalence of p53 mutations is a rare event in cervical cancer. The correlation between p53 mutations and HPV or prognosis is controversial. Loss of heterozygosity (LOH) of p53 is more commonly found in cervical cancer and is related with the prognosis of this disease. There is no significant correlation between p53 polymorphism and development of cervical cancer. The p53 mutations were not commonly found in cervical cancer. LOH of p53 may contribute to the progression of this malignancy. p53 polymorphism failed to be an independent prognostic factor in predicting the outcome of patients with cervical cancer. Further, epidemiologic surveys should be undertaken in larger populations and in different geographical regions.     

宫腔诊刮组织中p16、p53病理表达与子宫内膜癌的高危因素及预后的关系

目的:探讨宫腔诊刮组织中p16、p53表达与子宫内膜癌的高危因素及预后的关系.方法:分析118例子宫内膜癌患者术前宫腔诊刮组织中及术后病理标本中p16、p53的免疫组化病理表达,并对其长期随访.结果:118例子宫内膜癌患者中p16及p53的病理表达率分别为26.3%和25.4%,两者的病理表达与高的FIGO分期,浆液性/透明细胞性癌组织学亚型相关.p53的病理表达还与绝经状态,高的病理分级有关.p53、p16在诊刮组织中的表达与子宫切除术后标本中的表达明显相关.p53与p16两者均正常表达者的5年生存率为84%,p53及p16病理表达的5年生存率分别为50%及52%,两者均病理表达的5年生存率仅为13%.结论:宫腔诊刮组织中p16、p53的病理表达可作为术前对高危型子宫内膜癌进行预测评估的有效生物学指标之一.     

采用组织阵列技术检测卵巢肿瘤组织中p53蛋白的表达

目的　采用组织阵列 (tissuearray)技术检测p5 3蛋白在卵巢肿瘤中的表达情况。方法　采用组织阵列技术结合链霉菌抗生物素蛋白 过氧化物酶连接 (SP)法对 5 2例不同卵巢组织进行p5 3蛋白检测。结果　卵巢癌中p5 3蛋白的表达率为 33% ,正常卵巢、卵巢良性肿瘤及卵巢交界性上皮肿瘤中表达率为 0 % (P <0 0 0 5 ) ;p5 3蛋白的过度表达与患者的不同年龄、病理分化程度无显著相关性 (P >0 0 5 ) ,而与不同组织类型具有显著相关性 (P <0 0 5 )。结论　组织阵列技术是研究肿瘤基因的一种新方法 ,具有高效、简便及标准化的特点。p5 3蛋白在卵巢癌中的表达率较其他类型的卵巢组织明显升高     

p53 is correlated with low BMI negative progesterone receptor status and recurring disease in patients with endometrial cancer

Objective

P53 tumor suppressor gene plays a role in endometrial carcinogenesis. Former studies described correlations between p53 protein overexpression in endometrial cancer and prognostic factors, measured by immunohistochemistry. But data is still controversial. The aim of this study was to measure p53 and phospho-p53 overexpression by Western blot and evaluate correlations between overexpression and prognostic and clinical factors. Phospho-p53 seems to be the functional p53 protein and was examined for the first time in endometrial cancer.

Methods

40 patients with endometrial cancer were included in the study. A control group of 20 patients with normal endometrial tissue samples was used. Western blot was performed for detection of p53 and phospho-p53. Clinical and pathological parameters were obtained from medical records. Statistical analysis was performed using the log-rank test, the Mann-Whitney test for two independent groups and the Fisher’s exact test for dichotomous groupings.

Results

In 17.5% of the patients with endometrial cancer a p53 overexpression could be evaluated. There was a correlation between a p53 overexpression and recurring disease (p: 0.014), a negative progesterone receptor status (p: 0.021) and a low BMI (p: 0.022). Only one of 40 patients had a phospho-p53 expression.

Conclusion

Western blot is a valid method for the detection of p53 overexpression. As other authors described before, p53 overexpression seems to correlate with negative prognostic factors. The correlation between p53 overexpression and a low BMI may underline the relationship between p53 alterations and biological aggressive endometrial carcinomas.     

卵巢克鲁根勃瘤p53蛋白表达的研究

分析胃肠道粘液腺癌转移至卵巢后Ｐ５３蛋白的表达。方法应用免疫组织化学ＢＳＡ法检测３２例卵的克鲁根勃瘤。结果阳性表达率４０．９％,且以３０岁以下,双侧肿瘤术后存活期短患者的高表达,有统计学意义。结论Ｐ５３蛋白作为独立因素影响卵巢克鲁根勃瘤的生物学行为患者的预后。     

p53 gene mutation is rare in human cervical carcinomas with positive HPV sequences

Chromosome 17p allelic losses and concurrent p53 mutations have been demonstrated in various human cancers. We therefore investigated the presence of chromosome 17p allelic loss and possible concurrent p53 mutation in 29 Korean cases of cervical carcinoma by restriction fragment length polymorphism (RFLP) analysis and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) over the region from exon 4 to exon 9 of the p53 gene. We also examined the expression of p53 in paraffin tissues by immunohistochemical staining and determined the incidence of human papillomavirus (HPV) sequences in the same tissues by multitype PCR analysis to correlate them to the allelic loss on chromosome 17p13 and p53 mutation. In the analysis of 29 cases, loss of heterozygosity (LOH) was observed in eight (40%) cases out of 20 informative cases and p53 mutation was observed in only one case (3.4%) at exon 5. So in the majority of cases with LOH on 17p in this series, mutation of p53 gene appeared to be rare. But we obtained three cases (10.3%) of positive immunoreactivity from 29 cases. Those cases may carry mutations outside of the regions examined by PCR-SSCP. HPV DNA was detected in 27 of 29 cases (93.1%). HPV types 8, 11, 16, and 18 were detected in the samples we tested, while only two (7.4%) out of 27 HPV positive cases exhibited overexpression for p53 without any demonstrable p53 mutation upon PCR-SSCP. These results suggest that HPV infection may play a role in inactivating wild-type p53 protein in cervical carcinomas. In conclusion, mutation and overexpression of p53 gene appear to be rare, particularly in cases of cervical carcinoma associated with positive HPV sequence.