Livin基因在浅表性膀胱癌中的表达及其与肿瘤复发的关系

目的检测凋亡抑制蛋白Livin在人浅表性膀胱移行细胞癌组织中的表达,并分析其与肿瘤分期、分级以及复发的关系。方法采用免疫组织化学法检测浅表性膀胱移行细胞癌(TCCB)组织标本中Livin蛋白的表达情况。结果Livin阳性表达率为57.5%,G1级阳性表达率53.8%,G2级阳性表达率59.3%,不同的病理分级组间表达差异无统计学意义(P0.05)。Ta期肿瘤阳性表达率为46.2%,T1期肿瘤阳性表达率为63.0%,不同临床分期组间表达差异无统计学意义(P0.05)。Livin表达与肿瘤是否多发无关。平均随访21.9个月,肿瘤复发率为55%,其中Livin表达阳性组的复发率为73.9%,平均复发时间为14.7个月,Livin表达阴性组复发率为29.4%,平均复发时间为31.58个月,二者之间差异显著(P0.05)。结论Livin在TCCB中高表达,Livin的表达与TCCB分级、分期及是否多发无关,与TCCB复发密切相关。     

survivin和环氧化酶-2在膀胱移行细胞癌组织中的表达及其相关性

目的 探讨膀胱移行细胞癌组织中凋亡抑制蛋白survivin和环氧化酶-2（cox-2）的表达与肿瘤生物学行为之间的关系及其二者的相关性。方法应用免疫组化Envision法，检测42例膀胱移行细胞癌组织标本和10例非肿瘤正常膀胱组织（正常对照组）中survivin和cox-2的表达。结杲42例膀胱移行细胞癌组织中survivin和COX-2表达的阳性率分别为78．6％和81．0％，正常对照组中均未见表达；survivin表达强度与肿瘤分期及复发呈正相关关系（P〈O．05），而与肿瘤分级无关（P〉O．05）；cox-2表达强度与肿瘤分级和分期呈正相关关系（P〈0．05），而与肿瘤复发无关（P〉0．05）；survivin和cox-2在膀胱移行细胞癌中的表达密切相关（rs=0．327，P〈0．05）。二者的表达与患者的性别、年龄、术时肿瘤的大小、数目及部位无关（P〉0．05）。结论Survivin和cox-2在膀胱移行细胞癌组织中普遍表达，且表达密切相关，二者可能在膀胱癌的发生、发展过程中起重要作用，并与浸润关系密切。     

基质金属蛋白酶2,9及金属蛋白酶组织抑制剂1在肾盂移行细胞癌中的表达及意义

目的 探讨基质金属蛋白酶2（MMP-2），9（MMP-9）及金属蛋白酶组织抑制剂1（TIMP-1）表达与肾盂移行细胞癌分级、分期及预后的关系。方法 采用免疫组化SP法检测117例肾盂移行细胞癌标本MMP-2，MMP-9发TIMP-1表达水平。患者中男97例，女20例。平均年龄59岁。肿瘤病理分级：G123例、G273例、G321例；TNM病理分期：Ta22例、T127例、T221例、T325例、T422例。结果 肾盂癌组织MMP-2表达阳性率81．2％（95例），MMP-9表达阳性率72．6％（85例），TIMP1表达阳性率72．6％（85例），阳性表达强度和阳性细胞分布不均匀，主要位于肿瘤细胞的胞质，随肿瘤分级、分期增加，MMP-2、MMP-9阳性表达率呈递增趋势，FL与预后相关，差异有统计学意义（P〈0．05）。TIMP-1阳性表达率随分级、分期增加呈递减趋势，但其差异无统计学意义（P〉0．05），TIMP-1表达强度与患者的生存时间无明显相关性。单因素方差分析发现MMP-9／TIMP-1比值与肿瘤临床病理分级、分期密切相关，随着分级、分期增加呈递增趋势（P〈0．05）。结论 MMP-2及MMP-9检测在肾盂癌病理分级、分期中有重要价值。MMP-2、MMP-9及MMP-9／TIMP-1比值在肾盂癌的预后判断中有重要意义。     

原肌球蛋白1在膀胱移行细胞癌中的表达及其临床意义

目的:探讨原肌球蛋白1(TM1)在膀胱移行细胞癌中的表达及其临床意义。方法:采用免疫组织化学SP法对48例膀胱移行细胞癌及8例正常膀胱组织黏膜中TM1的表达进行观察。结果:8例正常对照组织中,TM1呈高水平表达;而48例膀胱移行细胞癌组织中,44例(91.7%)TM1呈低水平表达。两者间TM1表达差异有统计学意义(P<0.01),但是TM1的表达与肿瘤分级分期无明显相关性。结论:TM1在肿瘤组织中的表达明显降低,但与肿瘤分级分期无关,有可能成为早期诊断膀胱癌的一个新标志物。     

手助腹腔镜在上尿路移行细胞癌治疗中的应用

目的：探讨手助腹腔镜在肾输尿管全长切除术加膀胱袖套状切除术中的应用价值。方法：采用手助腹腔镜行肾输尿管全长切除术，加膀胱袖套状切除术治疗上尿路移行细胞肿瘤7例(其中经腹腔途径5例，经腹膜后途径2例)。病理类型均为移行细胞癌(肾盂移行细胞癌5例，输尿管移行细胞癌1例，肾盂和输尿管多发性移行细胞癌1例)。结果：7例手助腹腔镜手术均获成功。手术时间50～150min，平均97．5min；术中出血50～300ml，平均111．4ml；术后住院时间7～53d。结论：采用手助腹腔镜行肾输尿管全长切除术加膀胱袖套状切除术治疗上尿路移行细胞癌，是一种可选择的新的手术方式，与开放手术相比，具有损伤小、出血少、术后恢复快等优点。     

EphB4在膀胱移行细胞癌中的表达及其与肿瘤微血管密度的关系

目的：研究EphB4在膀胱移行细胞癌组织中表达的意义及其与肿瘤微血管密度（MVD）的关系。方法：应用免疫组织化学方法检测44例膀胱移行细胞癌组织中EphB4蛋白的表达，同时采用CD34标记微血管进行肿瘤MVD计数。结果：EphB4的表达与膀胱移行细胞癌的病理分级和临床分期呈正相关（P〈0．05）；EphtM阴性组与EphB4阳性组之间肿瘤MVD计数的差异具有统计学意义（P〈0．01）；EphB4阳性程度不同的两组间的差异无统计学意义（P〉0．05）。结论：EphB4的表达与膀胱移行细胞癌的恶性程度以及与肿瘤血管的形成均密切相关，有可能成为膀胱移行细胞癌靶向治疗的新靶点。     

环氧化酶-2基因在膀胱移行细胞癌组织中的表达及其意义

目的　探讨环氧化酶 2 (COX 2 )基因在膀胱移行细胞癌组织中的表达及其临床意义。方法　采用免疫组织化学酶标记链霉素亲和生物素法 (LSAB)对 78例膀胱移行细胞癌组织进行COX 2基因表达的检测。结果　在膀胱癌中COX 2主要呈胞核表达 ,染色阳性率为 5 6.41% ;COX 2表达与膀胱移行细胞癌组织分级、分期和预后呈高度正相关 (P <0 .0 1)。结论　膀胱移行细胞癌中COX 2异常表达与肿瘤分级、分期和疾病进展等生物学行为密切相关。     

维甲酸受体β在膀胱移行细胞癌中的表达及意义

目的探讨维甲酸受体β（retinoic acid receptor-beta,RAR-β）在膀胱移行细胞癌中表达的意义。方法应用免疫组织化学方法检测80例膀胱移行细胞癌组织标本中RAR-β的表达。病理分级：Ⅰ级26例,Ⅱ级22例,Ⅲ级32例;临床分期：T120例,T220例,T322例,T418例;其中复发性膀胱癌46例。以10例正常膀胱组织作为对照。结果10例正常膀胱粘膜组织中RAR-β均为强阳性表达。80例膀胱移行细胞癌中RAR-β阳性表达28例（35.0%）。RAR-β表达在病理分级Ⅰ级以及临床分期T1、T2期膀胱癌中表达较高;在复发性与非复发性膀胱移行细胞中的表达分别为17.4%和58.9%,差异显著（P〈0.05）。结论RAR-β在膀胱移行细胞癌组织中存在表达缺失,其表达缺失程度与肿瘤病理分级、临床分期及复发相关,有作为膀胱移行细胞癌预后指标的可能。     

血栓调节蛋白在肾脏肿瘤组织中的表达及临床意义

目的研究血栓调节蛋白（TM）在肾盂移行细胞癌及肾细胞癌中的表达及临床意义。方法选择40例不同分期、不同分级的肾盂移行细胞癌及20例不同分期、不同分级的肾细胞痛标本，应用免疫组织化学SP法研究TM的表达。结果40例肾盂移行细胞癌，TM表达者37例（92．5％），20例肾细胞癌，TM表达1例（5％），其两组表达率明显不同（P〈0．01）。肾盂移行细胞癌组织TM表达阳性细胞百分数随病理分级、临床分期的上升而下降（P〈0．01或P〈0．05）。另外TM表达阴性者再发膀胱癌发生率为66．7％，TM表达细胞百分数小于41．7％的患者中再发膀胱癌发生率为62．5％，TM表达细胞百分数大于41．7％的患者中再发膀胱癌发生率为3．4％，前两者与后者相比，其再发膀胱癌发生率明显升高（P〈0．01）。结论TM表达量与肾盂移行细胞癌的恶性程度、病程情况等生物学行为有关。TM表达阴性及TM表达阳性细胞百分数小于41．7％的肾盂移行细胞癌再发膀胱癌可能性大，应对此类肾盂移行细胞癌患者术后按膀胱肿瘤对待。TM可以作为一种瘤标来鉴别诊断肾盂移行细胞癌与肾细胞癌。     

凋亡抑制因子Livin在膀胱移行细胞癌组织中的表达及意义

目的：研究凋亡抑制蛋白家族(IAP家族)新的凋亡抑制因子Livin在膀胱移行细胞癌(BTCC)中的表达及其与肿瘤分级、分期、复发之间的关系。方法：采用免疫组织化学SP法,对54例BTCC和8例正常膀胱组织中Livin的表达情况进行检测,分析其在膀胱癌组织和非膀胱癌组织中的表达及其与肿瘤病理学分级、临床分期和患者复发情况的关系。结果：Livin在8例正常膀胱组织中均不表达,而在54例膀胱移行细胞癌组织中表达率为85．2%(P＜0．01)。Livin的表达和膀胱移行细胞癌的病理分级、临床分期、是否复发无明显相关(P＞0．05)。结论：细胞凋亡抑制因子Livin在BTCC组织中表达上调,提示Livin可能通过抑制细胞凋亡,对BTCC的发生发展起重要作用;Livin在膀胱癌中的高表达有望成为一种有效、敏感的瘤标,并为BTCC的基因治疗提供新的靶点。     

Apoptotic cell death and Smad4 expression in transitional cell carcinoma of the renal pelvis and ureter

PURPOSE: To investigate the frequency of apoptosis and the expression of Smad4 protein as well as their roles in transitional cell carcinoma (TCC) of the renal pelvis and ureter. METHODS: Apoptosis was detected by using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) technique in 34 formalin-fixed and paraffin-embedded specimens of renal pelvic and ureteral TCC. The expression of Smad4 was immunohistochemically studied. RESULTS: The incidence of apoptosis ranged from 1.10 to 3.75% with a median of 2.50% in TCC of the renal pelvis and ureter. The incidence of apoptosis was noted to be closely related to histologic grade but not to pathologic stage of the cancer. The expression of Smad4 was detected in six of 34 cases (17.6%). Regarding subcellular distribution, Smad4 protein was localized both in cytoplasm and nucleus of the cancer cells. In comparing the incidence of apoptosis with the expression of Smad4, no significant associations were seen between them. The expression of Smad4 was not related to the tumor grade nor stage of the cancer. CONCLUSIONS: The present study demonstrated close association of the incidence of apoptosis with the tumor grade of TCC of the renal pelvis and ureter. Significance of Smad4 expression was not noted in the study. It suggests that apoptotic cell death may play an important role in the tumor progression of renal pelvic and ureteral TCC.     

Prognostic variables in patients with transitional cell carcinoma of the renal pelvis and proximal ureter

Recent technological advances in urological endoscopic surgery of the renal pelvis and proximal ureter via ureteroscopy or percutaneous nephroscopy have made it possible to consider parenchymal-sparing procedures in patients with transitional cell carcinoma. To define the role of these procedures in the management of renal pelvic or proximal ureteral transitional cell carcinoma we analyzed retrospectively 31 patients who underwent nephroureterectomy for transitional cell carcinoma of the renal pelvis and/or proximal ureter. High grade upper urinary tract transitional cell carcinoma and a history of metachronous or synchronous bladder transitional cell carcinoma were independent adverse prognostic factors. However, patients with low grade upper urinary tract transitional cell carcinoma and no evidence of a urothelial field change had a 100 per cent 5-year survival rate. It would appear that parenchymal-sparing endoscopic techniques should be regarded with caution in patients with either high grade transitional cell carcinoma of the renal pelvis and proximal ureter or a history of bladder cancer.     

Estimations of the S phase fraction in situ in transitional cell carcinoma of the renal pelvis and ureter with bromodeoxyuridine labelling

This report concerns the estimation of the S phase fraction (SPF) in situ and its value in predicting the malignant potential of transitional cell carcinoma of the renal pelvis and ureter. Eighteen patients with transitional cell carcinoma of the renal pelvis and ureter were given a 0.5 h intravenous infusion of the thymidine analogue bromodeoxyuridine (BrdU) (500 mg) at the time of surgery to label tumour cells in the DNA synthesis phase. The tumour specimens were stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody as the first antibody. The BrdU labelling index, S phase fraction, was determined by counting the number of bromodeoxy-uridine labelled cells in the tissue sections. All grade 1 tumours had an S phase fraction lower than 10%. The average S phase fraction for non-invasive tumour (12 cases) and invasive tumour (6 cases) were 9.7 and 20.9%, respectively. Two patients with rapid spread of ureteric tumour showed an S phase fraction of 18.4 and 22.3%. The results obtained with the S phase fraction were comparable with histological tumour grade and invasive potential. The higher S phase fraction may indicate greater biological malignancy. We believe that determination of the S phase fraction of transitional cell carcinoma of the renal pelvis and ureter offers a new objective and quantitative assay of the biological potential of individual tumours and might have practical value in their management.     

Squamous cell carcinoma of the renal pelvis: nuclear deoxyribonucleic acid ploidy studied by flow cytometry

From 1944 to 1987, 28 patients with squamous cell carcinoma of the upper urinary tract were treated and also had tumor specimens that were fully evaluable by flow cytometric nuclear deoxyribonucleic acid ploidy analysis: 22 had squamous cell carcinoma of the intrarenal collecting system, 4 had tumors of the ureter, and 2 had tumors of the renal pelvis and ureter. Eight patients (29%) had deoxyribonucleic acid diploid, 11 (39%) tetraploid and 9 (32%) aneuploid ploidy patterns. Ploidy pattern significantly correlated with histological grade and tumor stage. Almost all tumors were histologically of high grade; among the patients with high grade tumors ploidy analysis separated fair and poor prognosis groups. Pathological stage was the dominant clinical variable. A total of 14 patients (50%) had advanced stage disease and all died within 12 months of diagnosis. Nearly all of these patients showed abnormal ploidy patterns and ploidy analysis was not useful prognostically for this group. In contrast, all 3 patients with squamous cell carcinoma of the renal pelvis who were long-term survivors had deoxyribonucleic acid diploid tumors. However, there is no clear statistical evidence from this study that ploidy analysis provides important prognostic information independent of stage and grade for patients with squamous cell carcinoma of the renal pelvis.     

Recurrence and prognosis of renal pelvic and ureteral carcinoma

Eighty-three patients with renal pelvic and ureteral carcinoma operated in Chiba University Hospital were followed. Age ranged between 23 and 79 years old (average 61.8 years) with the male-to-female ratio of approximately 2:1. Localization of tumors was in renal pelvis in 41 (49.4%), ureter in 29 (34.9%) and both in 13 (15.7%). Significant correlation in prognosis was obtained with macroscopic hematuria, histological classification, grade, stage and regional lymph node involvement. Recurrence was found on 49 cases (59%), 21 had intra-vesical tumor and 28 showed retroperitoneal recurrence or distant metastasis. In the former the mean tumor free interval was 14.8 months and 5 year survival rate was 62.1%. In the later the mean tumor free interval was 6.5 months and 3 year survival rate was 5%. 8 (38.1%) in 21 cases with low stage papillary transitional cell carcinoma showed recurrence and it was all intra-vesical tumor. 25 (56.8%) in 44 cases with high stage papillary transitional cell carcinoma showed recurrence. Retroperitoneal recurrence or distant metastasis was recognized in 12 cases. On the other hand 14 (87.5%) in 16 cases with non-papillary transitional cell carcinoma showed recurrence, which was all retroperitoneal recurrence or distant metastasis.     

The study on cell surface antigens in epithelial tumor of the upper urinary tract: ABH-isoantigen and Thomsen-Friedenreich antigen

ABH-isoantigen (ABH-Ag) and Thomsen-Friedenreich antigen (T-Ag) were investigated by the Avidin-Biotin-Peroxidase Complex (ABC) method on 47 patients with epithelial tumor of the upper urinary tract (all patients underwent nephroureterectomy including the cuff of the bladder; 30 patients were diagnosed as transitional cell carcinoma of renal pelvis and 17 ureteral organs). The correlations between ABC expression for ABH-Ag and T-Ag with histological grade, stage and prognosis (5 year survival rate) were studied. A correlation was observed between grade (p less than 0.05) and deletion of the antigenicity of ABH-Ag, but no correlation was evident with stage and prognosis. A high correlation was evident, however, between grade (p less than 0.01), stage (p less than 0.01) and prognosis (p less than 0.01) and deletion of the antigenicity of T-Ag. The analysis of ABC expression for ABH-Ag and T-Ag may therefore be valuable for predicting the malignant potential in transitional cell carcinoma of the upper urinary tract. T-Ag determination in particular may provide a useful prognostic probe should it find clinical application.     

Carcinoma of the renal pelvis and ureter. An investigation of 384 registered cases in the Tokai Urological Cancer Registry

Registration of renal pelvic and ureteral tumor was done from 1980 through 1986, in the Tokai Urological Tumor Registry. Among the 404 cases of the carcinoma, 384 cases (210 renal pelvis, 174 ureter) were subjected to the present study. A total of 319 cases (83.1%) showed a complete cure, while 20 cases (5.2%) were considered as partial cure, and 45 cases (11.7%) were classified to progressive disease group. Chemotherapy was performed on 151 patients including systemic administration to 141 patients (33.9%) and 11 patients received combined intravesical instillation therapy. Irradiation was performed on 49 patients (12.8%). Degree of histological and morphological differentiation of renal pelvis and ureter tumor were studied in 341 cases of transitional cell carcinoma (88.8%); G0, 0.3%, G1, 12.9%, G2, 49.3%, Gx, 5.2%. Stage of the tumor were T1, 33.6%; T2, 12.5%; T3, 14.6%; T4, 13.3%; Tis, 0.3%; Tx, 24.7%. Five-year relative survival for carcinoma of the renal pelvis was 46.6%, and for the ureter it was 53.1%. Five-year survival according to histological differentiation of transitional cell carcinoma and according to the stage of the tumor were as follows; G1, 91.6%; G2, 58.5%; G3, 27.2%; Ta, 84.6%; T1. 74.2%; T2, 48.5%; T3, 24.1%, T4, 7.3%. The rate of survival was correlated with histological differentiation of the tumor cells. The survival was poor in cases who had the components of squamous cell carcinoma and/or adenocarcinoma. Overall survived case were 177, 122 patients died of cancer, 20 patients died of other causes than cancer, and 1 patient died from immediate surgical effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simultaneous bilateral renal pelvic tumors: a case report]

A case of simultaneous bilateral renal pelvic tumors is reported. A 64-year-old man with the chief complaint of gross hematuria and left flank pain was admitted. Clinical investigations revealed a tumor in the right pelvis and ureter, and another tumor in the left renal pelvis. The right ureteral tumor had invaded the bladder. Right nephroureterectomy, total cystectomy, left partial pyelectomy and ureterocutaneostomy were performed. By pathological examination, right renal pelvic and ureteral tumors were non-papillary transitional cell carcinoma, grade 3, pT4, and the left renal pelvic tumor was papillary transitional cell carcinoma, grade 2, pT1. To our knowledge, this is the 16th case of simultaneous bilateral urothelial tumors of the upper urinary tract in Japan.     

Squamous cell carcinoma of the renal pelvis and ureter: incidence, symptoms, treatment and outcome

PURPOSE: Squamous cell carcinomas of the renal pelvis and ureter are rare. We report a large series of patients and compare it to patients with urothelial carcinoma. MATERIALS AND METHODS: The initial material was comprised of 808 patients with renal pelvis or ureteral cancer. A review of the histopathological material and clinical records was performed. RESULTS: Only 2 (4%) of 65 patients with squamous cell carcinoma had stage pTa/pT1/pT2 tumors compared to 460 (62%) of 743 patients with urothelial carcinoma. Median survival was much shorter for surgically treated patients with squamous cell carcinoma compared to those with urothelial carcinoma (7 vs 50 months). However, there was no significant difference in the disease specific 5-year survival rate between patients with squamous cell carcinoma and urothelial carcinoma in the same disease stage. Vascular invasion, microscopic solid tumor pattern and large tumor size had negative prognostic significance in multivariate analyses. Histopathological tumor type (squamous cell carcinoma or urothelial carcinoma) had no prognostic significance. CONCLUSIONS: The prognosis for squamous cell carcinoma is poor, but stage for stage the prognosis is not different between patients with urothelial carcinoma and squamous cell carcinoma of the renal pelvis and ureter. It can be presumed that high stage squamous cell carcinoma and urothelial carcinoma become symptomatic first at a time when the tumors already are large, deeply invasive and most often incurable. New treatment modalities are urgently needed to improve the poor prognosis in patients with advanced stage squamous cell carcinoma and urothelial carcinoma of the upper urinary tract.