FHIT、p21waf1/cip1基因在膀胱移行细胞癌中的表达与意义

目的通过测定脆性组氨酸三联体基因(FHIT)及p21waf1/cip1基因在膀胱移行细胞癌组织、正常膀胱组织中的表达,探讨FHIT基因以及p21waf1/cip1基因与膀胱癌的关系及其临床意义.方法采用免疫组织化学SP法对43例膀胱移行细胞癌(BTCC)组织及14例正常膀胱组织中的FHIT基因及p21waf1/cip1基因的蛋白表达进行检测.结果FHIT蛋白表达与肿瘤的分期、分级无相关性(P＞0.05)而p21waf1/cip1蛋白的表达与之有相关性(P＜0.05);FHIT蛋白的表达在GI肿瘤、浅表性肿瘤中明显低于在正常膀胱组织中的表达(P＜0.05)而p21waf1/cip1蛋白的表达在上述组织比较中无差别(P＞0.05);FHIT蛋白的表达在初发肿瘤中与复发肿瘤中无明显差别(P＞0.05)而p21waf1/cip1蛋白的表达在上述两种组织比较有明显差别(P＜0.05).FHIT蛋白与p21waf1/cip1蛋白的表达没有相关性(P＞0.05).结论FHIT基因可能成为早期诊断膀胱移行细胞癌的指标.p21waf1/cip1基因可能成为估计膀胱移行细胞癌的恶性程度及肿瘤侵袭性、预后的指标.FHIT基因在膀胱移行细胞癌中的作用机制可能与p21waf1/cip1基因没有关系.     

FHIT、p21^waf1/cip1基因在膀胱移行细胞癌中的表达与意义

目的：通过测定脆性组氨酸三联体基因（FHIT）及p21waf1/cip1基因在膀胱移行细胞癌组织、正常膀胱组织中的表达,探讨FHIT基因以及p21waf1/cip1基因与膀胱癌的关系及其临床意义。方法：采用免疫组织化学SP法对43例膀胱移行细胞癌（BTCC）组织及14例正常膀胱组织中的FHIT基因及p21waf1/cip1基因的蛋白表达进行检测。结果：FHIT蛋白表达与肿瘤的分期、分级无相关性（P〉0.05）而p21waf1/cip1蛋白的表达与之有相关性（P〈0.05）;FHIT蛋白的表达在GI肿瘤、浅表性肿瘤中明显低于在正常膀胱组织中的表达（P〈0.05）而p21waf1/cip1蛋白的表达在上述组织比较中无差别（P〉0.05）;FHIT蛋白的表达在初发肿瘤中与复发肿瘤中无明显差别（P〉0.05）而p21waf1/cip1蛋白的表达在上述两种组织比较有明显差别（P〈0.05）。FHIT蛋白与p21waf1/cip1蛋白的表达没有相关性（P〉0.05）。结论：FHIT基因可能成为早期诊断膀胱移行细胞癌的指标。p21waf1/cip1基因可能成为估计膀胱移行细胞癌的恶性程度及肿瘤侵袭性、预后的指标。FHIT基因在膀胱移行细胞癌中的作用机制可能与p21waf1/cip1基因没有关系。     

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.     

膀胱移行细胞癌RASSF1A和Cyclin D1与Bcl-2蛋白的表达及意义

目的:探讨RASSF1A、CyclinD1和Bcl-2蛋白在膀胱移行细胞癌发生发展中的作用,以及RASSF1A和CyclinD1与Bcl-2蛋白之间的关系。方法:免疫组化法(SP法)检测45例膀胱移行细胞癌组织、45例癌旁黏膜及18例正常黏膜组织中RASSF1A、CyclinD1和Bcl-2蛋白的表达。结果:膀胱移行细胞癌组织中RASSF1A、CyclinD1和Bcl-2蛋白表达阳性率分别为46.7%(21/45)、88.9%(40/45)和57.8%(26/45);癌旁组织分别为84.4%(38/45)、42.2%(19/45)和24.4%(11/45);正常组织分别为94.4%(17/18)、38.9%(7/18)和16.7%(3/18)。膀胱移行细胞癌组织中RASSF1A蛋白的表达显著低于癌旁及正常膀胱黏膜,P<0.05;而CyclinD1和Bcl-2蛋白的表达则显著升高,P<0.05。RASSF1A和CyclinD1及Bcl-2蛋白的表达呈负相关性,P<0.05。结论:RASSF1A蛋白的表达降低和CyclinD1、Bcl-2蛋白的过表达可能参与膀胱移行细胞癌的发生发展过程,RASSF1A可能通过某种机制促使CyclinD1和Bcl-2在膀胱移行细胞癌中过表达,从而促进膀胱移行细胞癌的发生发展。     

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。     

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。     

膀胱移行细胞癌p21WAF1／CIP1mRNA及蛋白的表达

目的 研究p21WAF1／CIP1基因在膀胱移行细胞癌中的表达及意义。方法 采用原位杂交及免疫组化技术检测56例膀胱移行细胞癌标本和10例正常膀胱黏膜组织p21WAF1/CIP1mRNA及蛋白的表达。结果 p21mRNA和p21蛋白在膀胱移行细胞癌中的阳性表达率分别为51．8％（29／56）,35．7％（20／56）;在正常膀胱黏膜中的阳性表达率均为10％（1／10）。它们在低分化,浸润性肿瘤的表达明显低于高分化,浅表性肿瘤（P＜0．05）。结论 p21WAF1／CIP1的表达同膀胱移位细胞癌的恶性程度呈负相关,它的低表达是膀胱移行细胞癌发生、发展中的晚期分子事件。综合运用原位分子杂交和免疫组化技术可以客观、准确地评价基因的功能动态。     

脆性组氨酸三联体与肺癌的临床病理学研究

目的:探讨抑癌基因FHIT在肺癌组织中的表达缺失及其与临床病理因素的关系.方法:采用免疫组织化学S-P法检侧40例肺癌组织中FHIT蛋白表达情况,以癌旁组织作对照.结果:FHIT蛋白表达阴性率在肺癌为65.00%(26/40),FHIT蛋白在肿瘤组织中的表达明显低于癌旁正常组织(P<0.05).其中鳞癌为38.46%(5/13),腺癌为77.78%(21/27),其差异有显著性(P=0.01).FHIT与组织学类型、分化程度及性别有相关性(P<0.05).与年龄、肿瘤大小、临床分期、有无淋巴结转移无关(P>0.05).结论:FHIT在肺癌中失表达或表达下降可能与肺癌的发生有相关性.     

凋亡相关蛋白Survivin及Fas在膀胱移行细胞癌中的表达及其临床意义

目的探讨凋亡相关蛋白Survivin及Fas在膀胱移形细胞癌表达及其临床意义。方法应用S-P免疫组织化学法检测45例膀胱移行细胞癌及10例正常膀胱黏膜组织石蜡切片中Survivin和Fas表达的情况,结合临床资料进行分析。结果Survivin在膀胱移形细胞癌标本中的表达阳性率为68.9%(31/45),而正常对照组中无一例呈阳性表达;Fas在膀胱移行细胞癌标本中的表达阳性率为46.7%(21/45),与对照组阳性率100.0%(10/10)相比,差异有显著性(P<0.05)。Survivin的表达与膀胱移行细胞癌的组织学分级、初发和复发显著相关(P<0.05),但与临床病理分期、肿瘤数目无关;Fas的表达与膀胱移行细胞癌的组织学分级、肿瘤数目、初发和复发相关,但与临床分期无关。相关性分析表明,膀胱移行细胞癌中survivin的表达与Fas表达呈负相关。结论Survivin在膀胱癌组织中选择性表达与膀胱移行细胞癌的分化程度密切相关,Fas蛋白在膀胱移行细胞癌中表达下降,survivin及Fas蛋白对于判断膀胱移行细胞癌预后有重要临床指导意义。     

膀胱肿瘤组织中Rb、E2F-1及P21的表达及其意义

目的:检测膀胱肿瘤组织中Rb、E2F-1及P21蛋白的表达,探讨三者在膀胱肿瘤组织发生和发展中的作用及临床价值.方法:采用免疫组织化学方法检测122例膀胱肿瘤组织中Rb、E2F-1及P21蛋白的表达.结果:在膀胱移行细胞乳头状瘤和膀胱移行细胞癌中Rb蛋白表达的阳性率分别为93.3%(28/30)和68.5%(63/92),膀胱癌组低于乳头状瘤组,组间差异有统计学意义(P=0.007).E2F-1、P21蛋白在膀胱癌与乳头状瘤组中阳性表达率分别为70.7%(65/92)、46.7%(14/30)和72.8%(67/92)、50.0%(15/30),膀胱癌组高于乳头状瘤组,组间差异有统计学意义(P=0.017;P=0.021).E2F-1和P21蛋白在膀胱癌组织中阳性表达率随组织分化程度的降低而升高.Spearman等级相关分析显示膀胱肿瘤组织中Rb与E2F-1、P21蛋白表达呈负相关(r=-1.000,P<0.05,r=-1.000,P<0.05);E2F-1和P21蛋白表达呈正相关(r=1.000,P<0.05).结论:Rb、E2F-1及P21蛋白的表达异常可能与膀胱移行细胞癌的发生发展有关,Rb、E2F-1及P21蛋白的联合检测可为诊断膀胱移行细胞癌及临床判断组织恶性程度提供参考.     

p27kip1、CyelinD1、CyelinE在膀胱移行细胞癌中表达的意义

目的探讨p27kip1、CyclinE、CyclinD1在膀胱移行细胞癌（BTCC）中的表达与意义,为认识BTCC发生、发展机制提供线索。方法应用免疫组织化学SP法检测41例BTCC和12例膀胱炎中p27kip1、CyclinE、CyclinD1的表达。结果p27kip1在BTCC中阳性表达随临床分期和病理分级的增高而降低（P〈0．05）,有淋巴转移组与无淋巴转移组比较差异无统计学意义（P〉O．05）。CyclinD1在不同BTCC临床分期和病理分级中的阳性表达差异无统计学意义（P〉0．05）。CyclinE在BTCC中阳性表达随临床分期和病理分级的增高而增高（P〈0．05）,有淋巴转移组明显高于无淋巴转移组（P〈0．05）。结论p27kip1对BTCC的发生、发展可能起抑制作用,CyclinD1过表达可能在膀胱移行细胞癌发生的早期起作用,不参与膀胱移行细胞癌的浸润转移过程。CyclinE可能参与BTCC的发生、发展过程。     

p21WAF1、Cyclin D1和PRb在膀胱移行细胞癌中的表达及其意义

目的 :探讨 p2 1WAF1、细胞周期蛋白 D1 (Cyclin D1 )和 PRb在膀胱移行细胞癌(BTCC)中的表达及相互关系及其意义。方法 :应用免疫组织化学 SP法检测 5 7例 BTCC患者癌组织中 p2 1WAF1、Cyclin D1 和 PRb的蛋白表达。结果 :p2 1WAF1、Cyclin D1 和 PRb的阳性表达率分别为36 .8%、49.1%和 45 .6 % ,p2 1WAF1随病理分级升高阳性率显著下降 ,Cyclin D1 和 PRb的表达与BTCC的病理分级、临床分期和有无转移均相关 ,p2 1WAF1与 PRb的表达呈负相关 ,Cyclin D1 和PRb的表达呈正相关 ,而 p2 1WAF1与 Cyclin D1 的表达无关。结论 :p2 1WAF1/ Cyclin D1 / PRb通路异常与 BTCC的发生发展密切相关 ,p2 1WAF1的改变可能为癌变的早期事件 ,联合检测 p2 1WAF1、Cyclin D1 和 PRb可较准确地评价 BTCC的生物学特性 ,估计预后 ,指导治疗     

Expression of p53 and p21waf1/cip1 in gastric carcinoma: lack of inter-relationship or correlation with prognosis.

AIMS: The cell cycle regulators p53 and p21waf1/cip1 are expressed variably in human cancers. We investigated their expression in gastric carcinoma and determined their inter-relationship and prognostic significance. METHODS: Immunohistochemistry was used to determine their expression in material from 100 resected specimens of gastric carcinoma, and comparison was then made of the degree of expression between each, with conventional clinicopathological indices and with survival. RESULTS: Positivity was found with p53 (40%) and p21 (75%). There was no significant correlation between the expression of each individual marker, nor between each marker and 5-year survival. There appeared to be an association between p53 expression and lymph node metastases, and a higher frequency of p21waf1/cip1 expression in males. CONCLUSIONS: The expression of p53 and p21waf1/cip1 as detected by immunohistochemistry were of no value in predicting the prognosis of patients with gastric carcinoma.     

Prognostic impact of p21/waf1/cip1 in colorectal cancer

In addition to the tumor suppressor gene p53, Cyclin Dependent Kinases (CDK) are well known to influence the cell cycle in normal human tissues and various neoplasias as well. The purpose of our present study was to evaluate the expression of the CDK-inhibitor p21/waf1/cip1 in colorectal cancer with special emphasis on the prognostic impact. Between 1985 and 1991, 294 patients (median age, 65 years) underwent surgical operative therapy for colorectal cancer. Formalin-fixed and paraffin-embedded tumor specimens were investigated. For immunohistochemistry the Catalysed Reporter Deposition (CARD) technique was performed. The survival probability was calculated and possible prognostic risk factors were tested using multivariate analysis. The p21/ waf1/cip1 staining pattern was positive in 197 (67%) specimens and negative in 97 (33%) samples. No significant correlation could been calculated between p21/waf1/cip1 expression and other variables such as age, sex, WHO-Classification, localisation, grading, TNM-classification or UICC-stage. Patients with a positive staining reaction had a significantly better survival (p < 0.0052). Moreover, p21/waf1/cip1 was shown to be an independent prognostic parameter by multivariate analysis (p < 0.022). In contrast with these findings, the p53 tumor status had no impact on survival. P21/ waf1/cip1 appears to be an independent prognostic parameter in colorectal cancer and is associated with a favorable survival. This feature may be related to a cell cycle arrest in the G1 phase induced by p21/waf1/cip1, resulting in lower tumor cell proliferative activity.     

Paradoxical correlations of cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1 in metastatic colorectal carcinoma.

The cyclin-dependent kinase inhibitors (CDIs) p27kip1 and p21waf1/cip1 are key cell cycle-negative regulatory enzymes. The objective of this study was to correlate expression of p27kip1 and p21waf1/cip1 with survival, chemotherapy responsiveness, and expression of the proliferation marker Ki-67 in patients with advanced colorectal cancer. Immunohistochemistry was performed with antibodies to p27kip1, p21waf1/cip1, and Ki-67 on samples from 66 patients with metastatic colorectal carcinoma. Interpretation was performed by visual inspection and automated image analysis. Patients who obtained a response to chemotherapy had greater p21waf1/cip1 tumor staining with a mean of 10.0 positive cells/high-powered field, compared with 4.5 positive cells/high-powered field for nonresponders (P = 0.03). A positive Spearman correlation was seen between Ki-67 and p27kip1 (r = 0.48; P = 0.0001), as well as between Ki-67 and p21waf1/cip1 (r = 0.48; P = 0.0001). A trend toward shorter survival was seen in patients with positive specimens (median survival of 10 months for patients with both p27kip1- and p21waf1/cip1-positive specimens, compared with 22 months for patients with neither p27kip1- nor p21waf1/cip1-positive specimens). In contrast to that previously reported in normal colonic mucosa or early-stage colorectal cancer, we observed positive correlations of Ki-67 with both p27kip1 and p21waf1/cip1, a trend toward greater CDI staining indicating worse prognosis, and greater p21waf1/cip1 staining in tumors that were chemosensitive. These findings suggest that in the metastatic setting, CDIs may show altered function, compared with their role in the normal cell cycle.     

Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival.

We have studied 118 renal cell carcinomas to analyse the expressions of cyclins A and D1 and p21(waf1/cip1), and their relationship to clinical and histopathological parameters as well as to clinical outcome. Cyclins A and D1 and cyclin-dependent kinase inhibitor p21 (waf1/cip1) were not expressed in normal renal tissue. Staining signals of cyclin D1 and p21(waf1/cip1) were always nuclear but cyclin A was also expressed in the cytoplasm of the tumour cells. The mean (range) fractions of cyclin A, cyclin D1 and p21(waf1/cip1)-positive tumour cells were 2.2% (range 0-20%), 23.3% (range 0-90%) and 6.8% (range 0-70%) respectively. The expression of cyclin A was related to venous invasion, high nuclear grade, high mitotic rate, high Ki-67 and high PCNA expressions (P < or = 0.006 for all). The expression of cyclin D1 was linked with age over 65 years, low nuclear grade and high p53 expression (P < or = 0.05 for all). An inverse correlation was present between p21(waf1/cip1) and cyclin D1 (P = 0.011). Cyclin A predicted survival in the entire study group (P = 0.0014), in T1-4/N0-2/M0 (P = 0.0007) and in T1-2/N0/M0 tumours (P = 0.0007). Cyclin A was also a powerful predictor of disease-free survival in T1-4/N0/M0 (P = 0.0027) tumours (P = 0.0007). Cyclin D1 and p21(waf1/cip1) were not significantly related to survival or disease-free survival in any of the groups. In the entire material the independent prognostic factors were the presence of distant metastases (relative risk (RR) 5.16, P < 0.001), T category (RR 2.68, P < 0.001), Ki-67 expression (RR 1.02, P = 0.026) and cyclin A expression (RR 1.12, P = 0.001). The independent predictors in T1-4/N0/M0 tumours were T-category (RR 2.67, P = 0.001) and cyclin A (RR 1.21, P < 0.001), and in T1-2/N0/M0 tumours the only significant predictor was cyclin A (RR 1.19, P = 0.0002). In renal cell carcinoma, cyclin A is a powerful and independent prognostic factor in all clinical stages of the disease, whereas cyclin D1 and p21(waf1/cip1) have no prognostic value.     

PTEN与FHIT在膀胱移行细胞癌中的表达及其临床意义

目的：探讨PTEN与FHIT在膀胱移行细胞癌（bladder transitional cell carcinoma,BTCC）组织中的表达及其临床意义。方法：应用免疫组化技术（SP法）检测62例膀胱移行细胞癌和13例正常膀胱黏膜标本中PTEN与FHIT蛋白的表达情况。结果：PTEN、FHIT蛋白在BTCC表达率分别为56.5%和51.6%,明显低于二者在正常膀胱黏膜中的表达,差异有统计学意义（P〈0.05）;在BTCC中PTEN与FHIT蛋白表达均与肿瘤病理分级和分期密切相关（P〈0.05）,在BTCC标本中PTEN蛋白表达与FHIT蛋白表达呈正相关（r=0.448,P〈0.05）。结论：PTEN、FHIT在BTCC的发生、发展中发挥了重要作用。PTEN、FHIT联合检测可作为预测BTCC生物学行为和预后判断的重要指标。     

p27kip1在膀胱移行细胞癌中的表达及其与肿瘤细胞增殖的关系

目的：探讨p27^kip1在膀胱移行细胞癌（BTCC）中的表达及其与肿瘤细胞增殖之间的关系。方法：应用鼠抗人p27^kip1和Ki-67单克隆抗体对65例BTCC和12例正常黏膜进行免疫组化S－P法染色。结果：p27^kip1在BTCC中表达随着临床分期和病理分级的增高而降低（P＜0．05），有淋巴结转移组明显低于无淋巴结转移组（P＜0．05）。p27^kip1阳性表达率与Ki-67呈负相关。结论：p27^kip1对BTCC的分化、增殖、浸润和转移可能起抑制作用。检测BTCC组织中p27^kip1和Ki-67蛋白表达对评价BTCC的生物学行为和判断预后具有重要意义。     

Cyclin E和p27~(kip1)在膀胱移行细胞癌中的表达及其意义

目的　探讨CyclinE和p2 7kip1在膀胱移行细胞癌 (BTCC)中的表达 ,并评价其相关性和意义。方法　应用鼠抗人CyclinE和 p2 7kip1单克隆抗体对 65例BTCC和 12例正常粘膜进行免疫组化SP法染色。结果　CyclinE在BTCC中阳性表达率随着病理分级 (P <0 .0 5 )和临床分期 (P <0 .0 1)的升高而增高 ,有淋巴结转移组非常显著高于无淋巴结转移组 (P <0 .0 1) ;而p2 7kip1在BTCC中的阳性表达率随着临床分期和病理分级的增高而降低 (P <0 .0 5 ) ,有淋巴结转移组显著低于无淋巴结转移组 (P <0 .0 5 )。CyclinE和 p2 7kip1在BTCC中表达具有负相关性 (r =-0 .2 62 ,P <0 .0 5 )。结论　CyclinE对BTCC的分化、增殖、浸润和转移可能起促进作用 ;而p2 7kip1则对BTCC的分化、增殖、浸润和转移可能起抑制作用 :两者在细胞周期进展中的共同表达失调 ,可能是导致BTCC发生发展和向恶性表型转化的机制之一。