膀胱移行细胞癌Mta-1基因与蛋白表达及其临床意义

目的:检测膀胱移行细胞癌(BTCC)中Mta-1mRNA与蛋白表达,分析其与BTCC临床分期、病理分级、转移及复发的关系。方法:原位杂交、免疫组化方法检测42例BTCC组织Mta-1mRNA与蛋白的表达;CD34标记血管内皮细胞,计数肿瘤组织微血管密度(MVD);结合临床病理资料,分析Mta-1与BTCC的侵袭转移、血管生成及复发间的关系。结果:①Mta-1mRNA与蛋白在BTCC中高度表达,其表达阳性率分别为78.6%、73.8%,与正常组织比较差异有统计学意义(P<0.01),且随BTCC临床分期及病理分级的升高而增加,肿瘤复发组高于无复发组,肿瘤转移组高于无转移组(P<0.05)。②经非参数相关分析发现,Mta-1蛋白与Mta-1mR-NA表达呈高度正相关,Rs为0.945,P=0.000;CD34标染的微血管密度(MVD)与Mta-1mRNA与蛋白表达亦呈正相关,相关系数分别为0.712、0.683,P=0.000。结论:①Mta-1在膀胱移行细胞癌中高度表达,并随着肿瘤临床分期和病理分级的升高而增加,与肿瘤的转移及复发密切相关。②Mta-1参与膀胱移行细胞癌的侵袭、转移,可能与促进血管生成有关。     

Interleukin-4 gene intron-3 polymorphism is associated with transitional cell carcinoma of the urinary bladder

OBJECTIVE: To evaluate whether polymorphism of the interleukin-4 gene exon 3, and of the interleukin-1beta gene exon 5 and promoter region, are associated with transitional cell carcinoma (TCC) of the urinary bladder, as cytokines are hypothesized to be important in cancer formation. PATIENTS, SUBJECTS AND METHODS: The study included 138 patients with TCC of urinary bladder and 105 healthy controls living in the same area. Each genetic polymorphism was typed using polymerase chain reaction-based restriction analysis. Genotype distribution and allelic frequencies between patients and controls were compared. RESULTS: There were significant differences in genotype and allelic distribution of intron 3 RP1/RP2 polymorphism (P < 0.001), but no significant difference in genotype distribution or allelic frequencies of the interleukin-1beta gene polymorphism between patients with bladder cancer and controls. CONCLUSION: The interleukin-4 gene intron 3 polymorphism is associated with bladder cancer and is a potential genetic marker in screening for the possible causes of bladder cancer.     

Clinical study of transitional cell carcinoma of the prostate associated with bladder transitional cell carcinoma

BACKGROUND: Transitional cell carcinoma of the prostate in patients with bladder cancer appears to influence the prognosis and affects the decision about therapeutic modality. Therefore, it is important to characterize transitional cell carcinoma associated with bladder cancer. METHODS: From April 1980 to December 1998, 81 male patients underwent total cystoprostatectomies for transitional cell carcinoma of the bladder. The 81 cystoprostatectomy specimens were examined to clarify the characteristics of prostatic involvement by transitional cell carcinoma. The extent, origin, mode of spread and risk factor of prostatic involvement as well as the prognosis were investigated. In 13 of 15 patients with prostatic involvement the prostate was examined by sequential step sections. RESULTS: Prostatic involvement was observed in 15 of 81 patients (18.5%). Prostatic urethral involvement, invasion to prostatic duct/acinus, prostatic stromal invasion and extraprostatic extension and/or seminal vesicle involvement were recognized in 12 (80%), 14 (93.3%), six (40%), and five (33.3%) of the 15 patients, respectively. Twelve of the 15 patients (80%) with prostatic involvement had papillary or non-papillary tumors (i.e. carcinoma in situ) both in the prostatic urethra and prostatic duct. In 10 of these 12 patients (88.3%), there was contiguity between prostatic urethral and ductal tumors. Seven of the 23 patients (30.4%) with carcinoma in situ of the bladder showed prostatic involvement, which increased to 50% in the presence of carcinoma in situ of the trigone or bladder neck. CONCLUSIONS: Eighty per cent of the patients with prostatic involvement showed papillary or non-papillary tumors both in the prostatic urethra and prostatic duct. There was a high level of contiguity between both tumors. Patients with carcinoma in situ of the trigone or bladder neck revealed significantly higher incidence of prostatic involvement.     

膀胱移行细胞癌Id-1表达的实验研究

目的　探讨正常膀胱移行上皮和不同分化程度膀胱移行细胞癌 (BTCC)Id 1的表达 ,分析膀胱癌生物学行为与Id 1的关系。方法　免疫组化ABC法检测 111例BTCC和 12例正常膀胱组织Id 1表达。结果　Id 1正常膀胱组织 3例表达阳性 ,阳性率 2 5 % ;BTCC 97例表达阳性 ,阳性率 87.38% ,膀胱癌G1、G2 、G3 阳性率分别为 88.89%、87.5 %、85 .72 % ,与对照组比较均有显著性差异 (P <0 .0 1) ,病理分级间无显著性差异 (P >0 .0 5 ) ;表浅性膀胱癌与浸润性膀胱癌表达阳性率分别为 82 .76 %、92 .4 5 % ,两者比较具有统计学意义 (P <0 .0 5 )。结论　膀胱移行细胞癌Id 1过表达 ;Id 1与膀胱癌发生和侵袭性有一定关系 ;Id 1可能作为膀胱癌的一种肿瘤标记物为膀胱癌的筛查、早期诊断和术后随访提供帮助。     

Human DNA topoisomerase-IIalpha expression as a prognostic factor for transitional cell carcinoma of the urinary bladder

OBJECTIVE: To investigate the immunohistochemical expression of topoisomerase II-alpha (TII-alpha, a nuclear enzyme, the expression of which increases rapidly at the end of the S to G2/M phase and declines when mitosis ends) in bladder urothelial neoplasms (transitional cell carcinoma), and its correlation with grade, stage and survival. PATIENTS AND METHODS: Histological sections from 57 urothelial neoplasms were stained immunohistochemically for TII-alpha expression; the percentage of positive cells in the area of greatest staining was recorded as the TII-alpha index. RESULTS: TII-alpha nuclear staining was positive in all the samples except one. The mean (sd) TII-alpha index was 10.7 (5.9) in urothelial neoplasms of low malignant potential (grade 1), 15.5 (5.0) in low-grade (grade 2) and 42.1 (13.4) in high-grade urothelial carcinoma (grade 3). The mean TII-alpha index was 10.7 (5.9), 26.3 (14.8) and 44 (19) in stages pTa, pT1 and pT2, respectively. The TII-alpha index was significant for predicting death from cancer, independently of the stage or grade of the disease (P = 0.019, hazard ratio 1.1). CONCLUSIONS: A higher TII-alpha index indicates a greater probability of recurrence of disease and lower overall survival. Therefore TII-alpha expression has prognostic value in bladder carcinoma.     

细胞角蛋白20表达与膀胱移行细胞癌复发的关系

目的　探讨细胞角蛋白 2 0 (CK2 0 )在膀胱移行细胞癌 (TCC)中的表达及临床意义。方法　应用免疫组化及图像分析技术检测 5 4例TCC中CK2 0的表达 ,并进行分组比较。结果　CK2 0的表达在有否复发组之间差异有极显著性意义 (P <0 .0 0 1)。结论　CK2 0的表达与TCC生物学行为密切相关 ,为临床预测TCC复发开辟了新方法。     

Extensive cutaneous metastasis of transitional cell carcinoma of the bladder

Cutaneous metastasis of bladder carcinoma is extremely rare. Iatrogenic implantations have been the main cause in the majority of cases of transitional cell carcinoma with cutaneous metastasis. Otherwise, primary cutaneous metastasis is accepted as the late manifestation of systemic spread. The present paper describes a case of relatively early and extensive skin metastasis of transitional cell carcinoma in a 78-year-old man. The patient had a histopathological diagnosis of poorly differentiated (grade III) muscle invasive transitional cell carcinoma with a staging of T2NOMO 6 months prior to presenting. He presented to our outpatient clinic with a 3-month history of skin lesions as multiple, rubbery subcutaneous nodules. Radiological reinvestigation revealed no other metastatic site (including bone and lung), except for a metastatic nodule in the liver. The present paper reports an interesting and rare case of extensive skin metastasis of transitional cell carcinoma as the primary complaint.     

糖蛋白(MUC1与MUC7)基因在膀胱移行细胞癌的表达研究

目的 探讨糖蛋白MUC1与MUC7基因在膀胱移行细胞癌（BTCC）组织及细胞株中的表达及意义。方法 采用MUC1与MUC7特异性巢式逆转录-聚合酶链反应（RT—PCR）对分离的4种组织标本及3种细胞株的mRNA样本进行检测。结果 所有4种组织标本及3种膀胱癌细胞株的MUC1基因表达均为阳性。MUC7基因表达仅见于3种膀胱癌细胞株和侵袭性移行细胞癌标本。半定量结果显示MUC1 mRNA基因表达在正常膀胱黏膜同腺性膀胱炎及各期膀胱癌之间差异有统计学意义（P〈0．05）。浅表性膀胱癌与侵袭性膀胱癌之间差异有统计学意义（P〈0．05）。不同细胞系BIU-87与T24之间表达差异无统计学意义（P〉0．05），耐药细胞株BIU-87／A同敏感细胞株BIU-87与T24之间表达差异有统计学意义（P〈0．05）。MUC7 mRNA基因表达在3种细胞株及侵袭性膀胱癌组织之间差异无统计学意义（P〉0．05）。结论 MUC1基因的上调表达与MUC7基因的差异性表达可能影响膀胱癌细胞的生物学行为，导致相应的临床后果-恶性转变、侵袭转移、耐药。MUC7基因表达是尿路上皮恶性侵袭性转化的开始。     

DNA芯片技术筛选膀胱移行细胞癌信号转导相关基因

目的探讨人膀胱移行细胞癌信号转导相关基因的表达变化。方法使用人肿瘤基因表达谱芯片检测11例膀胱移行细胞癌组织基因表达谱的变化，以寻找与细胞信号转导相关的差异表达基因。结果以正常膀胱黏膜组织为对照，11例膀胱肿瘤组织中有87个基因表达明显下调，102个基因表达明显上调。其中与细胞信号转导相关的差异表达基因有35个，明显上调基因13个，明显下调基因22个。结论膀胱肿瘤的发生与发展与多种细胞信号转导相关基因的异常表达有关。     

腹腔镜治疗上尿路移行细胞癌合并膀胱前列腺疾病

目的探讨腹腔镜治疗上尿路移行细胞癌合并膀胱前列腺疾病的临床效果。方法腹腔镜行肾输尿管全长、膀胱袖状切除和膀胱疾病处理及前列腺摘除术共10例。结果10例手术全部成功,术后无并发症,效果良好。随访3个月~3年未见局部复发和远处转移。结论该法不仅具有腹腔镜创伤小、恢复快的优点,且处理合并症简单,适合治疗上尿路移行细胞癌合并膀胱前列腺疾病。     

人膀胱浅表性移行细胞癌基因表达变化的基因芯片研究

目的研究人膀胱浅表性移行上皮细胞癌（TCC）和正常膀胱组织差异表达基因。方法应用基因芯片技术对6例膀胱浅表性TCC癌组织和正常膀胱组织的总RNA进行检测。结果在13939条目的基因中共发现差异表达基因720条。在癌组织中234条表达增加，486条表达降低；678条能在GeneBank中登录。结论膀胱浅表性TCC的发生、发展足多基因异常引起多条传导通路异常致使细胞恶性转化的结果，基因芯片技术可同时定量研究大量基因表达水平，是一种稳定、高效的方法。     

膀胱癌组织中程序性死亡配体-1的表达及其意义

目的：探讨程序性死亡配体-1（PD-L1）在膀胱移行细胞癌（BTCC）的表达及其意义。方法：采用免疫组织化学染色法,检测59例BTCC患者的癌组织及10例BTCC患者距离肿瘤组织3cm以外的正常膀胱粘膜组织中PD-L1的表达,逆转录聚合酶链反应技术（RT-PCR）检测30例BTCC患者的癌组织及其中10例距离肿瘤组织3cm以外的正常膀胱粘膜组织中PD-L1mRNA的表达,并对其表达水平与临床病理组织学参数之间的关系进行相关性分析。结果：正常膀胱粘膜组织中不表达PD-L1分子,而BTCC癌组织中免疫组化PD-L1阳性表达率为62．7％（37／59）,RT-PCR检测PD-L1 mRNA的阳性表达率为66．6％（20／30）。PD-L1的表达与肿瘤分期及淋巴结转移明显相关（P〈0．05）,但与患者的年龄、性别及分级无明显相关。结论：PD-L1BTCC组织中的高表达,可能在肿瘤的发生发展中起到一定的作用,有希望成为膀胱癌免疫治疗的一个新靶点．     

错配修复基因hMLH1在膀胱移行细胞癌中的表达及其意义

目的 观察错配修复基因hMLH1在膀胱移行细胞癌中的表达,探讨hMLH1与膀胱移行细胞癌的关系.方法 通过免疫组织化学方法 测定hMLH1在80例膀胱移行细胞癌中及20例正常膀胱组织中的表达.结果 hMLH1在膀胱移行细胞癌中的低表达率(32.5%)明显高于在正常膀胱组织中的低表达率(0%),差异有统计学意义(P＜0.05),且hMLH1在膀胱移行细胞癌中的低表达与肿瘤的分期分级有关(P＜0.05).结论 hMLH1的低表达与膀胱移行细胞癌的发生有关,与肿瘤的高分期和高分级有关,hMLH1的低表达在浸润性及分化差的膀胱移行细胞癌多见.     

Upper urinary tract transitional cell carcinoma: location is not correlated with prognosis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Tumour location has been shown to be of prognostic importance in UUT‐TCC, with tumours of renal pelvis having a better prognosis than ureteral tumours. Patients from Balkan Endemic Nephropathy (BEN) areas had a higher frequency of pelvis tumours. Also, we found that belonging to a BEN area is an independent predictor of disease recurrence.

OBJECTIVE

• ? To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT‐TCC).

PATIENTS AND METHODS

• ? A single‐centre series of 189 consecutive patients who were treated surgically for UUT‐TCC between January 1999 and December 2009 was evaluated.
• ? Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT‐TCC were excluded.
• ? In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour.
• ? Recurrence‐free probabilities and cancer‐specific survival were estimated using the Kaplan–Meier method and Cox regression analyses.

RESULTS

• ? The 5‐year recurrence‐free and cancer‐specific survival estimates for the cohort in the present study were 66% and 62%, respectively.
• ? The 5‐year bladder‐only recurrence‐free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P= 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non‐Balkan endemic nephropathy areas; 95% confidence interval, 1.37–5.98; P= 0.005) were associated with disease recurrence
• ? Tumour location was not associated with disease recurrence in any of the analyses.
• ? There was no difference in cancer‐specific survival between renal pelvis and ureteral tumours (P= 0.476).
• ? Using multivariate analysis, pT classification (HR, 8.04; P= 0.001) and lymph node status (HR, 4.73; P= 0.01) were the only independent predictors associated with a worse cancer‐specific survival.

CONCLUSION

• ? Tumour location is unable to predict outcomes in a single‐centre series of consecutive patients who were treated with radical nephroureterectomy for UUT‐TCC.

     

MMP2及MMP9在膀胱移行细胞癌尿液中的表达及与侵袭转移关系的研究

目的探讨MMP2及MMP9在膀胱移行细胞癌患者尿液中的表达,并研究它们与膀胱移行细胞癌侵袭转移之间的关系。方法采用酶联免疫吸附法(ELISA)定量检测尿液中MMP2及MMP9的含量,并分析其表达水平与膀胱移行细胞癌临床分期和病理分级之间的关系。结果MMP2在膀胱移行细胞癌患者尿液中的含量明显高于非癌症患者,二者差异有统计学意义(P<0.01);MMP9在膀胱移行细胞癌患者尿液中的含量也明显高于非癌症患者(P<0.01)。MMP9在膀胱移行细胞癌患者尿液中的含量与肿瘤临床分期呈显著正相关(r=0.51361,P<0.01);与肿瘤病理分级也呈显著正相关(r=0.47378,P<0.01)。MMP2在膀胱移行细胞癌者尿液中的含量与肿瘤临床分期呈正相关(r=0.32271,P<0.01);而与肿瘤病理分级不相关(r=0.29818,P>0.05)。MMP2和MMP9在膀胱移行细胞癌患者尿液中的含量呈显著正相关(r=0.55674,P<0.01)。结论膀胱移行细胞癌患者尿液中增高的MMP2及MMP9与肿瘤细胞侵袭能力密切相关。进一步研究对指导临床治疗、判断预后有重要意义。     

膀胱移行细胞癌患者RASSF1A蛋白表达和启动子区甲基化的研究

目的:探讨RASSFlA(RAS association domain family1A)蛋白表达水平与启动子甲基化的关系.方法:应用免疫印迹技术(western-blot)检测10例正常膀胱组织和23例膀胱移行细胞癌(Badder transitional cell carcinoma,BTCC)组织中RASSFlA蛋白表达水平;用甲基化特异性PCR(Methylation-Specific PCR,MSP)方法检测正常膀胱组织,BTCC组织中RASSF1A基因启动子CPG岛甲基化状态.结果:RASSF1A蛋白在正常膀胱组织中全部表达,在BTCC组织中表达率为30.4%(7/23),二组间表达差异有统计学意义(P＜0.05),但各肿瘤分期、病理分级间的表达差异无统计学意义(P＞0.05).在正常膀胱组织中,RASSF1A基因启动子未发生甲基化;在BTCC组织中,RASSF1A基因启动子甲基化频率为60.9%(14/23),二组间表达差异有统计学意义(P＜0.05).在14份启动子异常甲基化的BTCC标本中,13份同时伴有RASSFIA蛋白表达缺失或下调,两者存在明显相关性(P＜0.05).结论:RASSFlA基因启动子在BTCC组织中发生异常甲基化,使RASSF1A蛋白表达缺失,推测RASSFIA基因启动子CPG岛异常甲基化导致RASSF1A基因失活从而引起肿瘤的发生,而与肿瘤的进展可能无关.     

Oncological outcome of retroperitoneoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma

OBJECTIVE: To report the oncological outcome of retroperitoneoscopic nephroureterectomy (RNU) with bladder cuff excision for upper urinary tract transitional cell carcinoma (TCC), and to compare the outcome with that of the traditional open nephroureterectomy (ONU). PATIENTS AND METHODS: From January 2001, 48 patients with upper urinary tract TCC were enrolled in the study; 25 had RNU and 23 had ONU. Oncological parameters (disease-free survival and disease-specific survival) were calculated from the time of surgery to the date of last follow up and were analysed by the Kaplan-Meier method. RESULTS: Mean follow up was 24.3 months in the RNU group, significantly shorter than in the ONU group. Bladder recurrence was identified in two patients with grade 3 pathological stage pT3, one patient with grade 3 stage pT2 disease and two patients with grade 2 stage pT2 disease. Multiple organ metastases in the lung, liver and lymph nodes were associated with bladder recurrence in two cases (grade 2 stage pT3, and grade 3 stage pT3). The recurrence rate was 20% (5 of 25 cases) and mean time to recurrence was 9.5 months. In the ONU group, bladder recurrence and metastases developed in four and three patients, respectively. The recurrence rate was 17% (4 of 23 cases) and mean time to recurrence was 23.4 months. No significant difference was detected in the disease-free survival rate and cancer-specific survival rate between the two groups (P=0.759 and P=0.866, respectively). CONCLUSION: The oncological outcome of RNU appears to be equivalent to that of ONU. Moreover, long-term follow up is necessary to evaluate the oncological outcome in comparison to ONU.     

A comparison of the pathology of transitional cell carcinoma of the bladder and upper urinary tract

OBJECTIVE: To clarify the histopathological patterns of upper and lower urinary tract transitional cell carcinomas (TCCs), as previous reports suggest that upper urinary tract TCCs have a greater tendency towards high-grade disease than bladder TCCs, of which most are low-grade and low-stage tumours. PATIENTS AND METHODS: All patients presenting with TCC of bladder or upper urinary tract between February 1991 and December 2001 at one institution were identified. Further patient information was obtained from the hospital database and case-note review. RESULTS: In all, 164 patients with upper urinary tract TCC and 2197 with bladder TCC were identified. There was a correlation between grade and stage of both upper urinary tract and bladder TCCs. 35% of the upper tract TCCs were classified as grade 2 and 44% as grade 3, while for bladder TCCs, 31% of lesions were classified as grade 2 and 35% as grade 3 (P = 0.003). Of the upper urinary tract lesions 33% were stage pT2-T4, compared with only 20% of bladder TCCs (P = 0.001). CONCLUSIONS: Upper urinary tract TCC is a higher grade and stage disease than bladder cancer, a finding that emphasizes the need for aggressive treatment of upper urinary tract TCC. If endourological management of upper urinary tract TCC is considered, histopathological determination of tumour grade before treatment is essential.     

Contemporary management of stage T1 transitional cell carcinoma of the bladder

PURPOSE: Transitional cell carcinoma involving the lamina propria (stage T1) is associated with a high recurrence and progression rate with implications for patient survival and quality of life. A better understanding of the natural history of and treatment alternatives for this tumor may improve the outcome in patients with this stage of bladder cancer. MATERIALS AND METHODS: Literature of the last decade was comprehensively reviewed in regard to clinical and pathological diagnosis, adjuvant treatments, prognosis, and the role and timing of cystectomy. The information was gathered from MEDLINE, current urology journals, abstracts from recent urological meetings and personal experience. RESULTS: High grade and the depth of lamina propria invasion are important prognostic factors. Early diagnosis and accurate pathological assessment are essential for determining the most adequate treatment pathway. Initial treatment consists of complete transurethral resection and adjuvant treatment with intravesical instillation of bacillus Calmette-Guerin (BCG). Immediate postoperative instillation of mitomycin C decreases the risk of recurrence possibly related to tumor implantation. Intravesical treatment does not substantially decrease the chance of progression. Lack of a complete response to BCG at 3 to 6 months, high grade, the depth of lamina propria invasion, the association of carcinoma in situ and prostate mucosa or duct involvement represent significant predictors for progression. Cystectomy should be suggested for recurrent stage T1 tumor after BCG, new onset or persistent carcinoma in situ, tumor located at a difficult site for resection, prostatic duct or stromal involvement and muscle invasion. CONCLUSIONS: High grade stage T1 transitional cell carcinoma is a highly malignant tumor. Complete resection followed by immediate mitomycin C instillation and 6 weekly BCG instillations results in an acceptably low recurrence and progression rate. Rigorous long-term surveillance and continuous reconsideration of radical cystectomy in concordance with the evolution of the disease are essential.