Prognostic Significance of p53 Protein Accumulation in Stage pT1 Transitional Cell Carcinoma of the Bladder

Objective: Mutations in the tumour suppressor gene p53 results in the production of a mutant type, dysfunctional p53 protein which can readily be detected in the cell nucleus by immunohistochemical staining. This study aims to investigate the association of nuclear p53 protein accumulation with the clinical outcome of stage pT1 transitional cell carcinoma of the bladder which is renowned for high rates of recurrence and progression. Methods: TUR samples of the tumours from fifty-two patients with primary stage T1 bladder cancer were analyzed immunohistochemically using the standard avidin-biotin peroxidase method for nuclear p53 accumulation. Status of p53 immunostaining was correlated with tumour recurrence, disease progression and three-year survival of each patient. Results: The rate of tumour recurrence in pT1 bladder cancer was 36% in patients with tumours stained negatively for p53 protein and 78% in patients with tumours stained positively for p53 protein. Disease progression was seen in 15% of p53 (-) patients and in 56% of p53 (+) patients. Conclusions: In stage pT1 bladder tumours p53 nuclear accumulation indicates higher rates of tumour recurrence and disease progression. Accordingly, in patients who have pT1 bladder tumours with nuclear p53 accumulation, institution of more aggressive therapy should be considered and early radical therapeutic modalities should be offered to these patients.     

膀胱移行细胞癌EGFr的表达与预后相关性的研究

应用免疫组织化学方法对50例膀膛移行细胞癌中表皮生长因子受体(EGFr)表达进行研究。50例中EGFr表达阳性率为44％(22/50)。结果表明:浸润性肿瘤EGFr的阳性表达明显高于浅表性肿瘤;复发性肿瘤EGFr的阳性表达显著增高。结论;膀胱移行细胞癌EGFr的阳性表达与肿瘤临床分期和复发有相关性(P<0.05)。     

p53, bcl-2, and Bax Expression in Renal Cell Carcinoma

Objectives. Renal cell carcinomas often show a high degree of resistance to chemotherapy and radiation despite expressing normal function of the protein p53. The loss of control of apoptosis may also contribute to progression and resistance to treatment modalities and can be attributed to an interaction between p53 and the apoptotic regulators bcl-2 and Bax. To determine whether the expression of p53, bcl-2, or Bax could be correlated with outcome, we analyzed the expression pattern of these proteins in renal cell tumor samples.Methods. We examined 28 patients with clear cell renal cell carcinomas along with 7 patients with papillary renal cell carcinomas and 4 with renal oncocytomas. All renal cell carcinomas were clinically localized Stage pT2 with tumor size ranging from 4.0 to 10.3 cm (mean 6.23). Immunohistochemistry was performed on all samples and correlated with markers of outcome, including tumor grade, metastasis, recurrence, and overall survival rate.Results. In all clear cell tumors, the detection level of p53 expression was below the sensitivity of the assay, consistent with the reported infrequent incidence of p53 mutations in renal cell cancers. bcl-2 expression showed a significant correlation (P = 0.018) with higher tumor grade but could not be significantly correlated with other parameters examined including tumor recurrence, metastasis, or survival rate. The expression of Bax could similarly be correlated with higher tumor grade but with none of the other parameters.Conclusions. At the present time, the combination of both tumor grade and stage represents the best prognostic markers available. Adjunctive use of bcl-2 and Bax staining currently plays a minimal role in helping to further stratify patients at high risk for disease progression or recurrence.     

Correlation of Nuclear Morphometry and Immunostaining for p53 and Proliferating Cell Nuclear Antigen in Transitional Cell Carcinoma of the Bladder

Background :
In an attempt to determine the biological significance of nuclear morphometric findings, measurements of mean nuclear volume (MNV) and nuclear roundness factor (NRF) were compared to the immunoreactivityof p53 expression and proliferating cell nuclear antigen (PCNA) in human bladder cancer.
Methods :
MNV and NRF were measured using stereological methods. Expression of p53 and PCNA were determined by immunohistochemical staining. Specimens from 111 patients with previously untreated bladder cancer were analyzed.
Results :
The mean MNV was 235.8 ± 1 33.6 μm³ for the 81 patients with p53-labeling index (LI) less than 10% and 337.2 ± 141.0 μn³ for the 30 patients with p53 LI greater than 10% (P = 0.008). There was Resign if icant correlation between NRF and expression of p53. The mean MNV was 220.1 ± 1 20.5 μm³ for the 67 patients with PCNA LI less than 28% (the mean value of PCNA LI) and 328.9 ± 149.2 μm³ in 44 patients with PCNA LI greater than 28% (P= 0.0001). The mean NRF was 80.7 ± 4.2 for the 67 patients with PCNA LI less than 28%, and 82.3 ± 3.4 for the 44 patients with PCNA LI more than 28% (P= 0.04). Conclusion: Nuclear morphometric findings may reflect the proliferative potential of cancer eel Is of the bladder, as indicated by findings of immunostaining for p53 and PCNA.     

联合评估凋亡相关蛋白Survivin和突变型p53在膀胱移行细胞癌中的表达及意义

目的：探讨凋亡相关蛋白Survivin和突变型p53在膀胱移形细胞癌（BTCC）中的表达及其临床意义。方法：应用SP免疫组织化学法检测50例BTCC及10例正常膀胱黏膜组织石蜡切片中Survivin和p53表达的情况,结合临床资料进行分析。结果：Survivin在BTCC的肿瘤标本中的阳性表达率为76％（38／50）,而正常对照组中无一例呈阳性表达;Survivin的表达与BTCC的组织学分级、预后显著相关（二者均P〈0．05）,但与临床病理分期无关（P〉0．05）;p53在13TCC肿瘤标本中的阳性表达率为68％（34／50）,与对照组阳性表达率30％（3／10）相比有统计学意义（P〈0．05）。p53的表达与BTCC组织学分级、临床分期及复发相关（均P％0．05）;相关性分析表明,BTCC肿瘤组织中Survivin的表达与p53表达呈正相关（r=0．317,P〈0．05）。结论：Survivin在BTCC组织中选择性表达,与BTCC的分化程度及复发密切相关;p53蛋白在BTCC中的表达与分级、分期及复发相关,联合评估Survivin和p53蛋白对于判断BTCC预后有重要临床指导意义。     

膀胱癌错配修复基因hMSH2表达的研究

目的 探讨错配修复基因hMSH2在膀胱移行细胞癌中的表达情况及其与肿瘤细胞增殖、凋亡的关系.方法 采用免疫组化法检测101例膀胱移行细胞癌错配修复基因hMSH2以及细胞增殖抗原Ki-67的表达情况,原位末端标记(TUNEL)法检测肿瘤细胞凋亡情况.结果 hMSH2表达于非膀胱肿瘤尿路上皮及部分膀胱移行细胞癌的细胞核,膀胱移行细胞癌组低表达率较非膀胱肿瘤膀胱组织组高(P=0.004,＜0.05);膀胱移行细胞癌pT2-pT4组中hMSH2的低表达率比pTis-pT1组的低表达率高(P=0.016,＜0.05);G1、G2、G3三组间低表达率的总体差别有统计学意义(P=0.033,＜0.05),G1+G2组与G3组之间差别有统计学意义(P=0.036＜0.05);有无淋巴结转移组差别无统计学意义(P=0.317).hMSH2弱表达组与强表达组间凋亡指数(AI)均值差异非常显著(P＜0.01),Ki-67标记指数(Ki-67 LI)均值差异不显著(P＞0.05),AI/KI值差异经统计学分析具有统计学意义(P＜0.05).结论 hMSH2基因突变或功能缺失与膀胱移行细胞癌的发生有关,可能系肿瘤发生过程中的重要事件,并可能与肿瘤细胞凋亡有关,而与增殖活性无关.     

The Prognostic Importance of E-cadherin and p53 Gene Expression in Transitional Bladder Carcinoma Patients

Objective: The clinical course of transitional cell carcinoma is highly variable. The determination of sensitive prognostic factors for transitional cell carcinoma is very important. Therefore e-cadherin and p53 immunohistochemical activity can be used with other prognostic factors. Methods: The study comprised with 61 (4 women and 57 men) selected patients who had transitional cell carcinoma. Paraffin embedded tissue sections were investigated immunohistochemically for e-cadherin normal staining and p53 over expression. Results: It is seen that when grade and stages of illness increased normal staining of e-cadherin decreased and p53 over expressed. Abnormal e-cadherin was significantly associated with disease recurrence (P < 0.001), disease progression (P < 0.001) and bladder specific survival. p53 differentiation was not significant for disease recurrence (P > 0.05) inverse to prognosis of illness. Transurethral resectomy and BCG treatments were not effected e-cadherin and p53 activity within the groups statistically. Conclusion: Significant differences can be helpful to investigate patients more detailed pathologically. These expression rates in different type of transitional cell carcinoma patients may represent a biologically more aggressive cancer, requiring early definitive therapy. This hypothesis should be evaluated in larger studies and prospective clinical trials.     

膀胱癌性激素受体表达与复发率的关系

本文用荧光组织化学法测定了89例膀胱移行细胞癌雌雄激素受体的表达情况,有77例获长期随访,77例中有32例复发,总复发率为41.56％。采用乘积限法计算受体表达阳性各组及阴性组肿瘤复发率并进行比较。结果提示膀胱癌复发率随雌激素受体表达增多有下降趋势,但无统计学显著差异。雄激素受体表达阳性与否亦与肿瘤复发率无关。     

bcl-2 Expression in Prostate Cancer and its Relationship to Cell Cycle and Prognosis

Background: bcl-2 protein is an oncoprotein encoded by J protooncogene bcl-2 which is thought to be a key gene for the regulation of cell life and death. bcl-2 protein has been reported to be expressed in a subset of prostate cancers, and its biological role in this disedse has not yet been elucidated. This present study focused on the cell cycle analysis of bcl-2 immunoreactivity in prostate tumor samples and correlated findings with the prognosis of the patients.
Methods: Archival tissues from 37 prostate cancers were submitted for immunohistochemistry and DNA analysis via flow cytometry. All tissues were obtained before the patients received my treatment. Immunohistochemistry was performed using streptavidin biotin procedures, and DNA flow cytometry was done by J combination of two methods.
Results: Fourteen of 37 prostate cmcers (38%) exhibited bcl-2 immunoreactivity. bcl-2 positive prostate cancers significantly correlated with DNA aneuploidy and higher proliferation indices, but not with histological differentiation. Clinically, there was a poorer prognosis for patients with bcl-2 po sitive prostate cancer.
Conclusions: Our data indicates that bcl-2 protein expression in prostate canctv is associated with cell proliferation and may serve as a predictive factor for the prognosis of prostate cancer.     

Bulky Transitional Cell Carcinoma of Bladder with Inverted Proliferation

Two women, aged 51 and 62 years, had unusual transitional cell carcinomas of the urinary bladder which were > 5 cm and had a structural resemblance to inverted papilloma or Brunn's nest. They were treated by bladder-preserving surgery with no evidence of recurrence after 30 and 1 03 months follow-up, respectively. Our cases show some hitherto unrecognized aspects of transitional cell carcinoma with inverted proliferation because the tumors are usually found in males and tend to be aggressive.     

膀胱癌患者Ⅱ型环氧合酶和血管内皮生长因子的表达及意义

目的:探讨Ⅱ型环氧合酶(Cox-2)和血管内皮生长因子(VEGF)的表达与膀胱移行细胞癌(BTCC)生物学行为的关系。方法:应用免疫组化方法对139例BTCC以及36例正常膀胱组织中的Cox-2和VEGF进行检测。结果:Cox-2的阳性率在T_(a～1)和T_(2～4)分别为34.3%和75.0%(P0.001);Ⅰ级和Ⅲ级的表达率分别为33.9%和81.8%(P0.001)。VEGF的阳性表达率在T_(a～1)和T_(2～4)分别为23.9%和79.2%(P0.001);Ⅰ级和Ⅲ级的表达率分别为32.2%和84.8%(P0.001)。BTCC组织中COX-2与VEGF表达呈正相关(r=0.607,P0.05)。结论:Cox-2和VEGF可以作为了解BTCC生物学行为的有效指标。     

人丝氨酸蛋白酶抑制因子HAI-1在膀胱移行细胞癌中的表达及意义

目的 检测HAI-1基因在膀胱移行细胞癌(BTCC)中的表达,探讨与BTCC临床病理参数间的关系及其临床意义.方法 应用免疫组化SP法检测HAI-1在BTCC及正常膀胱黏膜中的表达,并结合临床病理资料分析.结果 HAl-1在BTCC及正常膀胱组织中均有表达;在BTCC中的表达阳性率明显低于正常膀胱组织,差异有统计学意义(P＜0.001);HAI-1表达随肿瘤病理分级、临床分期的升高、肿瘤转移的发生而显著性降低(P＜0.001).结论 HAI-1异常表达在BTCC的发生发展过程中可能具有重要作用,HAI-1蛋白可作为判断BTCC恶性程度及预后的新型生物学标记.     

膀胱移行细胞癌组织环氧化酶2和基质金属蛋白酶2 mRNA的表达及相关性

目的:探讨膀胱移行细胞癌组织环氧化酶2(COX-2)和基质金属蛋白酶2(MMP-2)mRNA的表达及两者的相关性。方法:应用RT-PCR方法检测42例膀胱移行细胞癌组织(其中Ta~T1期18例,T2~T4期24例;G1级12例,G2级19例,G3级11例;有转移26例,无转移16例)和5例正常对照膀胱组织COX-2、MMP-2 mRNA的表达,并分析与肿瘤分级分期和转移的关系以及两者的相关性。结果:COX-2 mRNA在Ta~T1期相对表达量为1.038±0.484,T2~T4期为1.489±0.584,均显著高于正常对照膀胱组织(0.460±0.224,P均<0.05);COX-2 mR-NA在G1、G2、G3级分别为0.920±0.442,1.338±0.584,1.632±0.515,均显著高于正常对照膀胱组织(0.460±0.224,P均<0.05)。MMP-2 mRNA在Ta~T1、T2~T4期分别为1.107±0.384,T2~T4期为1.604±0.425,均显著高于正常对照膀胱组织(0.423±0.227,P均<0.05);MMP-2 mRNA在G1、G2、G3级分别为0.971±0.370,1.445±0.378,1.755±0.387,均显著高于正常对照膀胱组织(0.423±0.227,P均<0.05)。COX-2与MMP-2 mRNA表达在有转移及无转移肿瘤组织中分别为1.591±0.455vs0.815±0.430,1.676±0.339vs0.927±0.228,P均<0.01。COX-2与MMP-2 mRNA的表达呈显著正相关(r=0.703,P<0.01)。结论:COX-2与MMP-2 mRNA在膀胱移行细胞癌组织高表达,且随肿瘤分级分期及转移而表达增加,二者在膀胱移行细胞癌的发生发展过程中可能具有协同作用。     

Exposure to Vinorelbine Inhibits in Vitro Proliferation and Invasiveness of Transitional Cell Bladder Carcinoma

Purpose

To study the effect of vinorelbine (VNR) on in vitro cell proliferation, invasiveness, cell adhesion to substrate, cell motility and metalloproteinase secretion of MB-49, a murine transitional cell carcinoma of the bladder (TCC).

Materials and Methods

The colorimetric MTS assay, which depends upon viable versus nonviable mitochondria, was used to evaluate the effect of graded concentrations of VNR on in vitro MB-49 cell growth. Chemoinvasion and cell motility were studied in TCC cells exposed for 24 hours to a noncytotoxic dose of VNR, through their ability to migrate across Matrigel -coated or Type IV collagen-coated 8-micrometer. pore filters. Zymographic studies in gelatin-embedded polyacrylamide gels were done to investigate gelatinolytic activity in conditioned media from treated and untreated MB-49 cells.

Results

Vinorelbine inhibited MB-49 cell growth in a dose-dependent manner (IC₅₀ 40 ng./ml.). In vitro cell invasive capacity of MB-49 cells pretreated for 24 hours with VNR at noncytotoxic doses (1 and 10 ng./ml.) was significantly lower than that of untreated cells. The decreased invasion of VNR-treated cells was not accompanied by a diminished adhesion to Matrigel (R) or type IV collagen nor by a significant reduced secretion of gelatinolytic metalloproteinases. Instead, motility of MB-49 cells exposed to noncytotoxic concentrations of VNR was inhibited in a dose-response fashion similar to that of invasion.

Conclusion

Vinorelbine proved to be an effective drug to inhibit tumor cell growth and invasion in a transitional cell bladder carcinoma model. The results obtained would justify preclinical studies to evaluate the effectiveness of VNR as a potential treatment of TCC.     

Case report: Microcystic Transitional Cell Carcinoma of the Urinary Bladder

We report a rare case of microcystic transitional cell carcinoma involving the urinary bladder, in a 38-year-old man, and we add our experience in the treatment of this neoplasm. The tumor was muscle invasive, and a radical cystectomy was performed. The patient received no postoperative chemotherapy or radiotherapy, and he has not signs of local recurrence or distal metastasis after 3 years of intense follow up. Even though the number of cases documented so far, is insufficient to draw safe conclusions regarding the optimal treatment of the microcystic variant of transitional cell carcinoma. Our case indicates that even in cases of microcystic transitional cell carcinoma with infiltrative nature, aggressive therapy is associated with good control of the disease locally and distally.     

OPN在膀胱移行细胞癌中的表达及临床意义

目的通过检测骨桥蛋白(osteopontin,OPN)在膀胱移行细胞癌(transitional cell carcinoma of the bladder,TCCB)组织及癌旁正常膀胱组织中的表达情况,探讨其在肿瘤组织中的表达与肿瘤的临床分期、病理分级之间的关系,为临床病理诊断及预后判断提供一定的理论依据。方法收集2010年1月至2015年9月在本院泌尿外科手术切除的TCCB组织标本65例,应用免疫组织化学S-P法对65例TCCB组织以及10例癌旁正常膀胱组织标本进行OPN的检测,结合这些患者的临床病历资料进行分析:(1)OPN在TCCB组织与癌旁正常膀胱组织中的表达差异;(2)OPN在TCCB组织中的异常表达与TCCB的临床分期、病理分级之间的关系。结果 OPN在TCCB组织中的阳性表达率为47.7%,在癌旁膀胱正常组织中不表达,其阳性表达率与TCCB的病理分级和临床分期密切相关(P0.05)。结论 OPN对TCCB的病理诊断有一定的意义,可能与TCCB的发生存在一定的关联,可作为TCCB病理诊断的标记物之一;同时,OPN可作为TCCB临床分期及病理分级的一项客观指标,可能与肿瘤的侵袭及转移密切相关,可以帮助判断患者的预后。     

Detection of C-ERBB-2 Amplification in Transitional Cell Bladder Carcinoma Using Competitive PCR Technique

Purpose

We used competitive PCR to verify retrospectively the prognostic significance of c-erbB-2 oncogene amplification in transitional cell bladder carcinomas as a predictive index of patient survival with a maximum follow-up of nine years, and to investigate the variations of c-erbB-2 amplification during bladder carcinoma recurrence and/or progression from superficial to more invasive states.

Materials and Methods

Oncogene amplification was determined by an accurate and sensitive procedure based on competitive PCR. Measurements were performed in DNA extracted from fresh cancers or from formalin-fixed, paraffin-embedded tumor samples.

Results

The overall mean incidence of c-erbB-2 oncogene amplification was 26 percent (24/92), with a significant relationship with tumor grade (p less than 0.001). We did not find any statistical difference in survival probability between subjects with (20 percent) or without (30 percent) oncogene amplification. During tumor progression we observed a limited increase of tumors carrying oncogene amplification (2 of 20) whereas the mean degree of amplification was not affected.

Conclusions

c-erbB-2 amplification seems to be a genetic event related to the degree of bladder tumor differentiation. However the presence and/or the degree of this genetic alteration do not seem predictive of tumor progression, recurrence and survival probability, at least in patients with advanced transitional cell bladder carcinoma. These data seem to indicate that the amplification of c-erbB-2 in bladder carcinoma could be considered as an epiphenomenon, present in a subset of tumors but apparently not related to the clinical outcome.