表浅膀胱癌Pgp与突变p53蛋白表达的相互关系及其共表达的意义

目的探讨表浅膀胱移行细咆癌中Pgp与突变p53蛋白表达的相互关系及其共表达情况在预测复发方面的价值.方法应用免疫组织化学SP法,检测46例随访3年以上、术前未经化疗的原发性表浅膀胱移行细胞癌中Pgp、突变p53蛋白表达情况.结果Pgp、突变p53蛋白的阳性表达率分别为45.7%、58.7%,PgP与突变p53蛋白的表达密切相关(P＜0.01);其中二者均阳性、其中之一阳性或均阴性表达率分别为34.8%、34.8%、30.4%,单因素Kaplan-Meier生存分析示Pgp与突变p53蛋白共表达情况与术后复发密切相关(P＜0.05).结论Pgp与突变p53蛋白共表达情况是判定原发性表浅膀胱移行细胞癌复发的重要指标.     

表浅膀胱癌Pgp、突变P53蛋白、bcl-2表达的预测复发价值

目的探讨Pgp、突变P53蛋白、bcl-2表达在预测表浅膀胱癌复发方面的价值.方法应用免疫组化SP法,检测46例随访3年以上、术前未经化疗的原发性表浅膀胱移行细胞癌中Pgp、突变P53蛋白和bcl-2表达情况.结果Pgp、突变P53蛋白、bcl-2的阳性表达率分别为45.7%、58.7%、37.0%,单因素Kaplan-Meier生存分析示Pgp、突变P53蛋白、bcl-2表达与术后复发相关(P值均<0.01);多因素COX回归分析示术后复发与Pgp、突变P53蛋白表达有关(P值均<0.05),而与bcl-2表达无关(P值>0.05).结论Pgp、突变P53蛋白表达是判定原发性表浅膀胱移行细胞癌术后复发的独立预后指标.     

膀胱癌中PGP、MDM2、p53基因表达的意义

目的探讨膀胱癌组织中Pgp、MDM2、p53基因表达的意义。方法采用免疫组织学方法检测83例膀胱移行细胞癌中Pgp、MDM2、p53基因表达的情况。结果Pgp阳性表达率为71.08%,p53阳性表达率为50.6%,MDM2阳性表达率59.03%,MDM2阳性表达与膀胱癌病理分级及临床分期呈负相关(γ=-0.263,P=0.016及γ=-0.388,P=0.001);p53阳性表达与膀胱癌病理分级呈正相关(γ=0.492,P=0.001);Pgp阳性表达与其病理分级及临床分期无相关性;Pgp、MDM2、p533种蛋白表达间无相关性。AI、p53、MDM2表达与患者5年生存率有关。结论检测Pgp可指导膀胱癌化疗药物的选择;运用膀胱癌临床分期及病理分级并检测其p53、MDM2表达,可判断膀胱移行细胞癌的预后。     

膀胱移行细胞癌P—gp表达与凋亡相关蛋白p53、bcl—2的关系

目的探讨膀胱移行细胞癌组织中MDR1基因产物P-gp表达与凋亡相关蛋白p53、bcl-2的相互关系及其临床意义.方法采用免疫组化S-P法检测107例原发性膀胱移行细胞癌组织中P-gp、p53、bcl-2蛋白的表达情况.结果P-gp、p53、bcl-2蛋白的阳性表达率分别为63.6%、72.9%、54.2%,三者的过度表达均与膀胱癌的病理分级、临床分期和术后腔内化疗后复发有关;P-gp表达与p53、bcl-2蛋白的表达密切相关(P＜0.01或P＜0.05).结论P-gp、p53、bcl-2蛋白的过度表达不仅是判定原发性膀胱移行细胞癌恶性程度和预后的重要指标,而且凋亡相关蛋白p53、bcl-2可能参与膀胱移行细胞癌多药耐药的形成.     

P33ING1、p53在膀胱移行细胞癌中的表达及与细胞凋亡的相关性

目的:探讨抑癌基因P33ING1在膀胱移行细胞癌(BTCC)中的表达及其与p53蛋白表达及细胞凋亡的相关性.方法:利用免疫组化S-P法和TUNEL.法检测83例BTCC及11例正常膀胱黏膜组织P33ING1、p53的表达及细胞凋亡指数(AI).结果:83例膀胱移行细胞癌组织中,P33ING1蛋白的阳性表达率为59.03%,而正常膀胱黏膜组织中P33ING1蛋白阳性表达率为90.9%.P33ING1蛋白表达与膀胱移行细胞癌的WHO肿瘤分级有相关性.spearman相关分析表明P33ING1蛋白表达与p53蛋白表达正相关(P<0.05).AI与P33ING1及p53蛋白表达无相关性.结论:P33ING1在膀胱移行细胞癌中表达下降可能在膀胱移行细胞癌的发生、发展过程中起重要作用,P33ING1与p53基因具有协同作用,同时检测p53的状态和P33ING1表达水平,对于膀胱癌的诊断、治疗和预后判断可能具有积极意义.     

P33ING1、p53在膀胱移行细胞癌中的表达及与细胞凋亡的相关性

目的：探讨抑癌基因P33ING1在膀胱移行细胞癌（BTCC）中的表达及其与p53蛋白表达及细胞凋亡的相关性。方法：利用免疫组化S-P法和TUNEL法检测83例BTCC及11例正常膀胱黏膜组织P33ING1、p53的表达及细胞凋亡指数（AI）。结果：83例膀胱移行细胞癌组织中,P33ING1蛋白的阳性表达率为59.03%,而正常膀胱黏膜组织中P33ING1蛋白阳性表达率为90.9%。P33ING1蛋白表达与膀胱移行细胞癌的WHO肿瘤分级有相关性。Spearman相关分析表明P33ING1蛋白表达与p53蛋白表达正相关（P〈0.05）。AI与P33ING1及p53蛋白表达无相关性。结论：P33ING1在膀胱移行细胞癌中表达下降可能在膀胱移行细胞癌的发生、发展过程中起重要作用,P33ING1与p53基因具有协同作用,同时检测p53的状态和P33ING1表达水平,对于膀胱癌的诊断、治疗和预后判断可能具有积极意义。     

P33ING1、p53基因在膀胱移行细胞癌中的表达及其意义

目的探讨抑癌基因P33ING1在膀胱移行细胞癌中的表达及其与p53蛋白表达的相关性。方法采用免疫组化S-P法,检测83例膀胱移行细胞癌及11例正常膀胱黏膜组织中P33ING1、p53的表达。结果83例膀胱移行细胞癌组织中P33ING1蛋白阳性表达率为59．03％,而正常膀胱黏膜组织中P33ING1蛋白阳性表达率为90．90％。P33ING1蛋白表达与膀胱移行细胞癌的WHO肿瘤分级相关。根据Spearman相关分析表明P33INGI蛋白表达与p53蛋白表达呈正相关关系（P〈0．05）。结论P33ING1基因可能在膀胱移行细胞癌的发生、发展过程中起重要作用,P33ING1与p53基因具有协同作用,同时检测p53和P33ING1表达水平,对膀胱癌的诊断、治疗和预后判断可能具有积极意义。     

环氧合酶-2与HER-2、p53在膀胱移行细胞癌中的表达及其相关性

目的探讨COX-2、HER-2和p53在膀胱移行细胞癌（BTCC）发生发展中其蛋白产物表达情况以及它们可能存在的相关性。方法采用免疫组织化学方法检测56例膀胱癌组织及10例正常膀胱组织中COX-2、HER-2和p53的表达情况。结果(1)56例膀胱移行细胞癌组织中COX-2、HER-2和p53阳性表达率分别为57.1%（32/56）、51.8%（29/56）和50%（28/56）,与正常膀胱黏膜组织中阳性表达率相比较,差异均有统计学意义(P <0.05),COX-2、p53和HER-2蛋白在膀胱移行细胞癌中的阳性率在肿瘤病理分级和临床分期间差异有统计学意义( P <0.05)。(2)COX-2的表达与HER-2、p53的表达呈正相关性( P <0.05)。结论COX-2、p53和HER-2的异常表达可能在膀胱移行细胞癌的发生发展中起一定的作用,膀胱移行细胞癌COX-2表达可能和HER-2、p53的异常表达具有密切关联性。     

Livinα在膀胱移行细胞癌组织中表达的研究

目的：研究膀胱癌相关Livin基因在膀胱移行细胞癌组织中的表达以及Livin基因表达与膀胱移行癌生物学行为的关系;研究抑癌基因p53在膀胱癌组织中突变以及Livin表达与p53基因突变的关系。方法：100例膀胱移行细胞癌组织,设计Livinα引物,以半定量RT—PCR的方法,检测膀胱癌组织LivinαmRNA,以免疫组化法检测癌组织中p53蛋白。将膀胱肿瘤病理分级、临床分期、是否复发等生物学行为及p53蛋白染色强度分别量化,与组织LivinαmRNA RT-PCR产物量进行等级相关分析。并以10例正常膀胱黏膜作为对照。结果：100例膀胱移行细胞癌,67例检测到LivinαmRNA表达,10例正常膀胱黏膜组织未检测到LivinαmRNA表达,LivinαmRNA在膀胱移行细胞癌组织中表达率高于正常膀胱黏膜,x^2=14．4,P=0．000。LivinαmRNA在膀胱癌组织中表达与p53蛋白阳性（rs=0．465,P=0．002）及肿瘤病理分级（rs=0．463,P=0．002）有相关性。结论：膀胱移行细胞癌组织中可见LivinαmRNA高表达,LivinαmRNA表达与膀胱癌病理分级及癌组织中p53蛋白呈正相关。     

膀胱癌细胞凋亡、P-gP、MDM2、p53基因表达的意义

目的:研究膀胱癌细胞凋亡、P-gp、MDM2、p53基因表达的意义。方法:采用免疫组化法及TUNEL法检测11例正常膀胱黏膜和83例膀胱移行细胞癌中P-gp、MDM2、p53基因的表达及细胞凋亡指数(AI)。结果:83例膀胱移行细胞癌中P-gp阳性71.08%,p53阳性50.6%,MDM2阳性59.03%,AI=1.4335±0.3863。MDM2阳性表达与病理分级及临床分期呈负相关(r=-0.263,P=0.016及r=-0.388,P=0.001);p53阳性表达与病理分级及临床分期呈正相关(r=0.492,P=0.001;r=0.341,P<0.01);P-gp阳性表达与病理分级及临床分期无相关性;P-gp、MDM2、p53 3种蛋白间表达无相关性;AI与MDM2呈负相关(r=-0.226,P=0.042);AI与病理分级及临床分期呈正相关(r=0.642,P=0.000;r=0.455,P=0.000);AI与P-gp、p53无相关性。AI、p53、MDM2的表达与5年生存率有关。结论:检测P-gp可指导膀胱癌化疗药物的选择;联合运用临床分期及病理分级并检测p53、MDM2可用于判断膀胱移行细胞癌的预后。     

P糖蛋白在胰腺癌中的表达及其与p21^ras和p53蛋白表达的关系

为了解Ｐ糖蛋白在原发和复发胰腺癌组织中的表达及其临床意义，并分析其表达与Ｐ２１＾ｒａｓ和Ｐ５３蛋白表达的关系，采用免疫组化泽４８例原发胰腺导管癌和１５例复发胰腺癌的石蜡包埋标本进行Ｐｇｐ，ｐ２１＾ｒａｓ蛋白和ｐ５３蛋白单抗的免疫组化染色。     

P-glycoprotein is not expressed in a majority of colorectal carcinomas and is not regulated by mutant p53 in vivo.

Overexpression of the MDR1 product, P-glycoprotein (Pgp), has been shown to be one of the mechanisms underlying the development of multidrug resistance (MDR). Recently, one mutant p53 has been shown to stimulate the MDR1 gene promoter in vitro, whereas wild-type p53 repressed this activity. We measured Pgp and p53 expression by immunoblotting in 34 colorectal tumours, and performed mutation analyses on the p53-positive tumours to confirm the presence of mutant p53 protein. Tumour DNA indices (DIs) were also measured using flow cytometry. Pgp was detected in 44% (15/34) of the tumours and in 100% (13/13) of the normal mucosas (P = 0.0005), with highest levels of expression seen in normal mucosa, suggesting that initial drug resistance in colorectal tumours is not caused by Pgp. Highly DNA aneuploid tumours demonstrated the lowest levels of Pgp expression relative to moderately aneuploid and diploid colorectal tumours. p53 protein was detected in 53% (18/34) of the tumours, and 12 of 14 p53-positive tumours had p53 gene mutations, p53-negative tumours had approximately twice the level of Pgp expression of p53-positive tumours. Pgp expression was not associated with either p53 expression (P = 0.73) or incidence of p53 gene mutation (P = 0.70), suggesting that mutant p53 does not induce Pgp overexpression in colorectal carcinomas.     

肺腺癌组织EGFR突变与p53和COX-2表达相关性及其临床意义

目的 针对表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变的酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗已成为肺癌精准治疗的典范,但多数患者在EGFR-TKI治疗有效后的8～16个月不可避免会出现获得性耐药.本研究探讨p53和COX-2在EGFR突变型晚期肺腺癌组织中的表达及其与患者临床特征的关系,并观察其表达对EGFR-TKI疗效的影响.方法 选取2014-03-01-2016-01-31于郑州大学第二附属医院病理确诊为EGFR突变型晚期肺腺癌并接受EGFR-TKI治疗的43例患者,利用免疫组织化学法检测p53和COX-2在EGFR突变型晚期肺腺癌组织中的表达;x2检验分析其与临床特征之间的相关性;生存分析采用Kaplan-Meier法;并进一步对影响患者无进展生存期(progression-free survival,PFS)的因素采用Cox比例风险回归模型分析.结果 43例EGFR突变型晚期肺腺癌患者中,p53、COX-2表达阳性率分别为41.8％和53.4％.p53表达随年龄增长(x2=3.939,P=0.047)及肿瘤分化程度减低(x2=4.182,P=0.041)而升高.COX-2表达与年龄、性别、吸烟史、肿瘤分化程度、临床分期及EGFR基因突变类型均未见明显相关性(P＞0.05).p53与COX-2表达无明显相关性,P＞0.05.患者接受EGFR-TKI治疗后,p53阴性组和阳性组中位PFS分别为12.0和7.5个月,差异有统计学意义,x2=4.726,P=0.030;COX-2阴性组和阳性组中位PFS分别为12.0和10.0个月,差异有统计学意义,x2=5.578,P=0.018.进一步行多因素Cox比例风险回归模型分析显示,p53 (HR=0.450,P=0.046)和COX-2(HR=0.424,P=0.021)表达均为EGFR突变型晚期肺腺癌患者PFS的独立影响因素.结论 EGFR突变型晚期肺腺癌组织中,p53和COX-2表达可能促进肿瘤进展,有望成为EGFR-TKI疗效的预测因子.     

P‐glycoprotein is positively correlated with p53 in human oral pre‐malignant and malignant lesions and is associated with poor prognosis

P‐glycoprotein (Pgp) encoded by the MDR1 gene, a predictor of chemoresistance, may also serve as a prognosticator of clinical outcome in cancer patients. The mutant tumour‐suppressor p53 protein has been shown to activate the MDR1 promoter, whereas the wild‐type p53 represses this activity in cultured cells. We have described the differential expression of Pgp and p53 proteins in betel‐ and tobacco‐related oral tumorigenesis in the Indian population. Herein, Pgp expression was analysed in relation to p53 protein accumulation in pre‐malignant and malignant oral lesions by immuno‐histochemical and flow‐cytometric analyses. The relationship between Pgp and p53 protein accumulation and clinico‐pathological parameters as well as prognosis was determined. Expression of Pgp was observed in 81% of oral squamous cell carcinomas (SCCs) and 71% of pre‐malignant lesions. Sixty‐five of 75 p53‐positive oral SCCs and 21/24 p53‐positive pre‐malignant lesions showed expression of Pgp. Significant correlation between Pgp and p53 expression was found not only in oral SCCs but also in pre‐malignant lesions. Co‐expression of Pgp and p53 proteins was indicative of poor prognosis. Follow‐up studies of 35 patients showed that 7 of 10 oral SCCs with accumulation of Pgp and p53 proteins also exhibited shorter disease‐free survival (recurrence/metastases). Our findings provide clinical evidence for a significant association between Pgp and p53 protein expression in oral tumorigenesis and may account for the aggressive nature of the tumour and poor prognosis. Int. J. Cancer (Pred. Oncol.) 84:80–85, 1999. © 1999 Wiley‐Liss, Inc.     

P-Glycoprotein Is Positively Correlated with p53 Protein Accumulation in Human Colorectal Cancers

To explore the relationship between mutant p53 and Pgp expression, we have examined the levels of both proteins in human colorectal adenocarcinomas. Serial frozen sections of 40 surgical samples were stained with an anti-Pgp (MRK16) and two different anti-p53 protein antibodies (Abs), PAb421 and Pabl80l. Nineteen (47.5%) of 40 samples examined were positive for Pgp, and 18 (45%) of 40 were positive for p53. The samples that stained positively with PAb421 also stained positively with Pahl80l. Pgp expression was detected in 13 (76.5%) of 17 samples that were positive for p53 using PAb421 and in 15 (83.3%) of 18 samples that were positive for p53 using Pabl80. Thus, we found that p53 and Pgp were co-expressed in a significant number of samples ( P < 0.002). There was no relationship between Pgp or p53 protein accumulation and histologic grade or stage. The present results demonstrate that Pgp expression is closely associated with p53 protein accumulation in human colorectal cancers. These data provide evidence to support the idea that mutant p53 activates the MDR1 gene in vivo .     

Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: a report from the Radiation Therapy Oncology Group

PURPOSE: Erb-1 (epidermal growth factor receptor, EGFR) and Erb-2 (Her-2) are two of the best characterized members in the EGFR pathway. In many tumor types, overexpression of these proteins is associated with enhanced malignant potential. Our objective in this study was to investigate the clinical relevance of EGFR and Her-2 expression in bladder cancer cases from four prospective Radiation Therapy Oncology Group (RTOG) bladder preservation trials using cisplatin-containing chemoradiation (RTOG 8802, 8903, 9506, and 9706). METHODS AND MATERIALS: Tumors from 73 cases from patients with muscle-invading T2-T4a bladder cancers had slides interpretable for EGFR staining; 55 cases had slides interpretable for Her-2 staining. Additionally, the respective prognostic values of p53, pRB, and p16 immunostaining were concomitantly examined. Staining and interpretation of staining were done in a blinded manner, without knowledge of clinical outcome. Staining was judged as positive or negative. Subsequently, staining was correlated with clinical outcome. RESULTS: On univariate analysis, EGFR positivity was significantly associated with improved overall survival (p = 0.044); disease-specific survival (DSS) (p = 0.042); and DSS with intact bladder (p = 0.021). There was also a trend for association between EGFR expression and reduced frequency of distant metastasis (p = 0.06). On multivariate analysis adding tumor stage, tumor grade, whether a visibly complete transurethral resection of bladder tumor (TURBT) was done or not, and patient age to the model, EGFR positivity was significantly associated with improved DSS. On univariate analysis, Her-2 positivity was significantly associated with reduced complete response (CR) rates (50% vs. 81%, p = 0.026) after chemoradiation which remained significant on multivariate analysis. The other markers examined in this study were not found to have any prognostic value in this setting. CONCLUSION: Epidermal growth factor receptor expression appears to correlate significantly with improved outcome in bladder cancer, whereas Her-2 expression is significantly associated only with reduced CR rates after chemoradiation. Further investigations are warranted into how EGFR family members regulate response to chemoradiation in bladder cancer and their potential therapeutic implications.     

Comparison of the expression of P-glycoprotein, Ki-67, and P-53 to technetium-99m tetrofosmin mammoscintigraphic findings

Adjuvant and neoadjuvant chemotherapy is being used increasingly in the treatment of breast cancer patients. However, drug resistance plays an important role in the failure of chemotherapy in breast cancer. The aim of this study was to compare technetium-99m tetrofosmin (Tc-TETRO) mammoscintigraphic findings with the expression of drug resistance proteins (p-glycoprotein [Pgp], Ki-67 and mutant p53) in human breast cancer tissues. Thirty patients diagnosed with infiltrating ductal breast cancer underwent Tc-TETRO mammoscintigraphy before surgery or biopsy. Protein expression was investigated by immunohistochemical analyses on multiple nonconsecutive sections from surgery or biopsy specimens. Tumor to background (T/B) ratios calculated by Tc-TETRO mammoscintigraphic findings were correlated with protein expression determined by immunohistochemical analyses. The Tc-TETRO T/B ratios were significantly lower for tumors in 12 patients with positive Pgp expression than for those in 18 patients with negative expression (1.19 +/- 0.13 and 1.94 +/- 0.33, p value < 0.01). However, differences in Tc-TETRO T/B ratios between the patients with positive and negative Ki-67 or mutant p53 expression were not found in this study. Our data confirmed that Tc-TETRO mammoscintigraphic findings are useful for determination of the presence of Pgp expression in breast cancer patients, but no significant relations between Tc-TETRO mammoscintigraphic findings and Ki67 or mutant p53 were found.     

The survival outcomes of patients with resected non-small cell lung cancer differ according to EGFR mutations and the P21 expression

The aims of this study were to evaluate the prognostic implications of patients with epidermal growth factor receptor (EGFR) mutations and a p21 expression, and to determine their associations in resected non-small cell lung cancer (NSCLC) patients. We sequenced exons 18-21 of the EGFR tyrosine kinase domain by performing mutation analysis of tissues from patients that suffered with NSCLC and who also had undergone surgical resection. The expressions of p21 and p53 were analyzed using immunohistochemistry. We detected EGFR mutations in 24 of 97 patients (25%). EGFR mutations were more frequent in the people who had never smoked than in the smokers (33% versus 14%, respectively; P=.028). The presence of EGFR mutations had no effect on survival. The expression of p21 in the patients with wild-type EGFR tended to be associated with better survival. However, the expression of p21 in the patients with EGFR mutations was associated with poor overall survival (P=.006). The five-year survival rates were 17% for the patients with EGFR mutations and p21 positivity (Group I), 44% for the patients with wild type EGFR (Group II), and 75% for the patients with EGFR mutation and no p21 positivity (Group III) (P=.036). Multivariate analysis that was corrected for age, gender and cancer stage revealed different overall survival outcomes according to the three groups (P=.004). There was no significant correlation between the expressions of p21 and p53. Survival outcomes in the patients with resected NSCLC may be correlated with the presence of a p21 expression and EGFR mutations.     

Supratentorial glioblastoma in adults: Identification of subsets and their clinical correlation

The concept of different genetic pathways leading to glioblastoma multiforme (GBM) has gained considerable acceptance, and two major groups are now described, primary or de novo GBM and secondary GBM. The present study was undertaken to elucidate whether additional pathways exist and to determine whether there is any correlation between these different variants and clinical parameters, such as age, duration of symptoms, and outcome. For this purpose, immunophenotyping was performed to study the simultaneous expression of p53 protein and epidermal growth factor receptor (EGFR) in 58 cases of adult supratentorial GBM. By this method, four variants of GBM could be distinguished: 34% were p53 positive only, 38% were EGFR positive only, 14% were double negative (p53 negative/EGFR negative), and 14% were double positive (p53 positive/EGFR positive). Interestingly, all nine cases of secondary GBM in which there was clinical and histological evidence of progression from a preexisting low-grade lesion were p53 positive. Differences were observed with regard to the age distribution of the four variants, in that the p53 negative/EGFR negative tumors occurred most frequently in the younger age group (21–40 years). In the elderly group (61–80 years), two-thirds of the tumors were p53 negative/EGFR positive primary GBMs, and no case of the double positive or double negative variant was encountered. The differences in duration of symptoms and symptom-free survival according to age group and genetic subset were not statistically significant. There were no differences in outcome within each age category for any GBM variant, although the longest mean symptom-free survival was noted among patients aged 41–60 years with the p53 positive/EGFR negative variant. This study therefore indicates that at least four subsets of GBM exist, but despite different genotypes, the biologic behavior remains similar. Other genetic alterations therefore need to be investigated to identify prognostic makers.