Second primary malignancies associated with renal cell carcinoma histological subtypes

PURPOSE: Renal cell carcinoma has been linked to numerous secondary malignancies. We evaluated the risk of secondary malignancies by renal cell carcinoma histological subtype in patients with clear cell, papillary and chromophobe renal cell carcinoma. MATERIALS AND METHODS: We studied 2,722 patients who underwent nephrectomy for sporadic renal cell carcinoma at our institution between 1970 and 2000. All specimens were reviewed by a single urological pathologist for histological subtype. Associations of second primary malignancies by histological subtype were evaluated using the chi-square and Fisher exact tests. RESULTS: Of the patients studied 2,188 (80.4%) had clear cell, 378 (13.9%) had papillary and 128 (4.7%) had chromophobe renal cell carcinoma. Patients with papillary renal cell carcinoma were significantly more likely to have colon cancer (p = 0.041), prostate cancer (p = 0.003), any second malignancy (p <0.001) and multiple malignancies (p <0.001) compared with patients with clear cell renal cell carcinoma. In addition, patients with chromophobe renal cell carcinoma were significantly more likely to have colon cancer than patients with clear cell renal cell carcinoma (p = 0.020). Although patients with papillary renal cell carcinoma were more likely to have bladder cancer, the incidence did not differ significantly compared with that in patients harboring clear cell and chromophobe renal cell carcinoma (p = 0.193). We did not find a significant difference in the incidence of breast cancer, lung cancer, rectal cancer or lymphoma among histological subtypes. CONCLUSIONS: Our data indicate that patients with papillary renal cell carcinoma are more likely to harbor secondary malignancies, including colon and prostate cancer, than patients with clear cell renal cell carcinoma. These results may have important implications for patient education and followup evaluation, and they should prompt mechanistic investigations.     

The predictive value of muscularis mucosae invasion and p53 over expression on progression of stage T1 bladder carcinoma

PURPOSE: We determine the significance of muscularis mucosae invasion and nuclear p53 over expression on the progression of stage T1 transitional cell bladder cancer. MATERIALS AND METHODS: The pathological findings in 149 cases of T1 tumors diagnosed between 1973 and 1996 were reviewed. Diagnosis was stage T1 in 94 tumors in which the muscular layer was clearly identifiable and disease-free. Mean followup was 64.9 months (range 5 to 288). T1 bladder cancers were subclassified into 2 groups, with (T1b) or without (T1a) muscularis mucosae invasion. The p53 nuclear antibody immunoreactivity was determined with antibody D07 and a cutoff point at 15%. RESULTS: T1 subclassification was possible in all 94 patients. Of all tumors 37.2% expressed p53 nuclear over expression. Univariate statistical analysis showed that p53 expression (p <0.05) and tumor invasion depth (p <0.001) significantly correlated with progression. However, on multivariate analysis only invasion depth (p <0.0001) and associated carcinoma in situ (p <0.03) remained independently significant as predictors of progression. CONCLUSIONS: In our study the depth of tumor invasion was a significant independent predictor of progression in patients with T1 bladder cancer. This result suggests that the depth of invasion in stage T1 should be included in the histopathological report.     

p53,CD34,E-钙粘蛋白在膀胱癌中的表达及判断预后的价值

目的　探讨 p5 3、CD3 4 、E 钙粘蛋白 (E cadherin)在膀胱移行细胞癌中的表达及判断膀胱癌预后的价值。　方法　采用免疫组化方法检测 4 6例膀胱移行细胞癌和 8例正常膀胱粘膜标本p5 3、CD3 4 、E cadherin的表达情况。　结果　 4 6例膀胱癌标本中p5 3、E cadherin的异常表达率分别为2 1.7%和 4 5 .6 %。p5 3异常表达在表浅型膀胱癌为 9.1% ,浸润型为 33.3% ,差别有显著性意义 (P <0 .0 5 ) ;病理Ⅰ～Ⅱ级异常表达 7.1% ,Ⅲ级 4 4 .4 % ,差别有显著性意义 (P <0 .0 0 5 ) ;复发组异常表达89 % ,未复发组 15 % ,差别有显著性意义 (P <0 .0 0 5 )。E Cadherin的异常表达率在浅表型膀胱癌为77.3% ,浸润型为 33.3% ,差别有显著性意义 (P <0 .0 0 5 ) ;在Ⅰ、Ⅱ级膀胱癌为 71.4 % ,Ⅲ级为2 7.8% ,差别有显著性意义 (P <0 .0 0 5 ) ;在复发组与未复发组分别为 18.0 %和 6 1.0 % ,差别有显著性意义 (P <0 .0 1)。CD3 4 在膀胱癌中的异常表达率为 4 1.3% ,在不同分期分级及复发与未复发组之间的表达差别均无显著性意义。　结论　p5 3和E Cadherin的异常表达与膀胱癌的恶性程度及复发密切相关 ,可作为判定肿瘤预后和复发的分子生物学指标     

Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2

PURPOSE: We investigated the association of the apoptosis related proteins Bcl-2, Bcl-x, Bax and Bak, p53, the adhesion molecule E-cadherin, the receptor proteins epidermal growth factor receptor and c-erbB-2, and the proliferation markers proliferating cell nuclear antigen and Ki-67 with the clinical outcome of bilharzial related transitional cell carcinoma and squamous cell carcinoma. MATERIALS AND METHODS: Cystectomy specimens from 109 patients with organ confined, muscle invasive stage, pT2pN0M0, bilharziall positive bladder cancer were examined, including 60 with squamous cell carcinoma and 49 with transitional cell carcinoma. Immunohistochemical results were correlated with tumor progression. RESULTS: In squamous cell carcinoma but not in transitional cell carcinoma the loss of epidermal growth factor receptor, Bax and Bak was significantly associated with higher histological grade (p = 0.02, 0.006 and 0.01, respectively). On univariate analysis patients with transitional cell carcinoma had a poorer prognosis than those with squamous cell carcinoma. p53 Over expression and the loss of Bak positivity were associated with shortened progression-free survival in transitional cell carcinoma (p = 0.006 and 0.04, respectively), and squamous cell carcinoma (p = 0.00001 and 0.04, respectively). In squamous cell carcinoma high tumor grade (p = 0.02) and in transitional cell carcinoma high labeling indexes for MIB-1, Bcl-x expression and c-erbB-2 positivity (p = 0.03, 0.02 and 0.04, respectively) were associated with a poorer prognosis. On multivariate analysis p53 emerged as a significant prognostic factor for each condition. Additional independent prognostic factors were proliferating cell nuclear antigen for squamous cell carcinoma, and MIB-1, Bcl-x and Bax for transitional cell carcinoma. CONCLUSIONS: Bilharzial related transitional cell carcinoma and squamous cell carcinoma of the bladder differ in interims of protein expression and prognosis. Independent prognostic factors were p53, MIB-1, Bcl-x, and Bax in the former disease, and p53 and proliferating cell nuclear antigen in the latter disease.     

Synchronous triple urogenital cancer (renal cancer,bladder cancer,prostatic cancer): a case report

A case of synchronous triple urogenital cancer, which was comprised of renal cell carcinoma of the left kidney, transitional cell carcinoma of the urinary bladder, and adenocarcinoma of the prostate, is reported. A 72-year-old Japanese male patient was referred to our outpatient clinic with the complaint of asymptomatic hematuria. At that time, his serum of level of PSA was elevated to 20 ng/ml. Cystourethroscopy showed a papillary bladder tumor and coagula through the left urinary orifice. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass lesion measuring about 6 cm by 5 cm in the left kidney. Angiography showed a hypervascular lesion measuring about 6 cm by 5 cm at the same site. Double cancer, consisting of renal cell carcinoma and transitional cell carcinoma of the urinary bladder, was suspected and we performed left total nephroureterectomy, hilar lymphadenectomy, and transurethral rection of the bladder tumor, one month later. At the same time, we performed a biopsy of the prostate. Histological diagnosis was renal cell carcinoma, clear cell carcinoma and transitional cell carcinoma of urinary bladder. Histological diagnosis of the prostate biopsy was moderately differentiated adenocarcinoma. Since this case fulfilled the criteria of Warren and Gates, it was classified as synchronous triple urogenital cancer. A review of the literature revealed 17 authentic cases of triple urogenital cancer, of which 14 and 10 cases were reported as a combination of renal cancer, bladder cancer and prostatic cancer, in the world and in Japan, respectively. Furthermore, he had been exposed to the atomic bomb explosion in Hiroshima in 1945. This carcinogenic precursor may be related to the development of the triple cancer.     

A case of synchronous triple primary carcinomas of the kidney,bladder and prostate

A case of synchronous triple carcinomas arising in the kidney, bladder and prostate is reported. An 82-year-old man had gross hematuria. Urine cytology was positive and intravenous pyelography showed right hydronephrosis with a filling defect in the bladder. Computed tomography revealed a 4 cm mass in the bladder, enlarged prostate and 6 cm renal mass at the left kidney. Cystoscopy demonstrated a papillary broadbased tumor with some small satellite tumors in the bladder, and magnetic resonance imaging revealed muscle invasion of the bladder tumor. This patient underwent left radical nephrectomy and total cystoprostatectomy with ileal conduit urinary diversion as radical treatment. Histological diagnosis was renal cell carcinoma, transitional cell carcinoma of the bladder. Furthermore, well-differentiated adenocarcinoma was found incidentally in the prostate. Immunohistochemical staining with anti-p53 antibody for the three tumors showed positive staining only for the bladder cancer.     

Familial papillary renal cell tumors and subsequent cancers: a nationwide epidemiological study from Sweden

PURPOSE: Familial risks in papillary renal cell carcinoma and association with second primary malignancies were studied using the nationwide Swedish Family Cancer Data Base. MATERIALS AND METHODS: Cancer data obtained from the Swedish Cancer Registry from 1961 to 1998 included 1,733 cases of papillary renal cell carcinoma. The standardized incidence ratio was used to measure cancer risk. RESULTS: Only 5 families were identified in which a parent had papillary renal cell carcinoma and an offspring had kidney cancer (nonsignificant SIR 1.51 for offspring). Discordant tumor sites associated with papillary renal cell carcinoma in the 2 generations were the upper aerodigestive tract and bladder (SIR 2.53, 95% CI 1.08 to 4.58 and 2.14, 95% CI 1.02 to 3.68, respectively). There was an overall increase in the risk of second primary malignancies of the lung, prostate and bladder and for non-Hodgkin's lymphoma and leukemia in patients with papillary renal cell carcinoma. The risk for a second primary tumor of the bladder associated with papillary renal cell carcinoma during the followup of 1 to 10 years was about 15 times higher than that associated with adenocarcinoma, which is the most common histological type of kidney cancer. The SIR was significantly higher in females than in males (59.67, 95% CI 40.23 to 82.94 versus 18.76, 95% CI 14.51 to 23.56). CONCLUSIONS: In addition to the familial association of these 2 cancer sites, the high risk of a second primary cancer of the bladder in patients with papillary renal cell carcinoma may reflect a common genetic alteration.     

MDM2、p53基因在膀胱癌中的表达及其临床价值

目的　探讨癌基因ＭＤＭ２ 和抑癌基因ｐ５３ 在膀胱癌中的表达及其临床价值。　方法　采用免疫组织化学方法对２３ 例膀胱癌标本进行检测。　结果　ＭＤＭ２ 、ｐ５３ 基因蛋白在肿瘤中阳性表达为３９ ％ 和４８ ％ ,与肿瘤分级分期,肿瘤复发性相关,两者异常表达呈负相关（ｒ＝ － ０ ．２ ９４６ ,Ｐ＜０ ．０５）。两者在癌旁组织中亦有一定表达率。　结论　ＭＤＭ２ 、ｐ５３ 基因的异常表达是膀胱癌中的基因事件,与膀胱癌发生发展密切相关,可作为临床判断肿瘤进展及可能预后的瘤标。     

A case of synchronous double primary cancers of prostate, and bladder in a hemodialysis patient: a case report

A 60-year-old male, who had been maintained on hemodialysis for 4 years, visited our hospital to receive living renal transplantation. He complained of macrohematuria, and preoperative examination showed elevation of psostate specific antigen (PSA). Cystoscopy revealed papillary tumors on the right lateral bladder wall. Transurethral resection of bladder tumor (TUR-Bt) was performed and histopathological examination showed transitional cell carcinoma, G2, pTa. The histologic diagnosis of the transrectal needle prostate biopsy specimen was moderately differentiated adenocarcinoma. Combined androgen blockade as a neoadjuvant therapy and radical prostatectomy were performed. A case of synchronous double primary cancers, comprised of adenocarcinoma of the prostate and transitional cell carcinoma of the urinary blader in a hemodialysis patient has never been previously reported in the Japanese literature.     

P53，C—erbB—2和bcl—2基因在膀胱癌中的表达及意义

目的：研究癌基因和抑癌基因蛋白产物在膀胱移行细胞癌组织中异常表达与肿瘤病理分级和临床分期之间的关系。方法：应用免疫组织化学方法检测96例膀胱移行细胞癌标本中P53,C－erbB-2和bcl-2基因的表达水平。结果：96例膀胱移行细胞癌标本中P53,C－erbB-2,bcl-2基因的阳性表达率分别为60．4％,66．7％和81．3％,P53,C－erbB-2和bcl-2异常表达与膀胱癌的病理分级和临床分期之间的差异有统计学意义（P＜0．01）,结论：P53,C－erbB-2和bcl-2基因异常表达在膀胱癌发生发展中起重要作用。肿瘤的多基因分析比单基因分析更有价值,为临床病理诊断及估计预后和复发提供了参考指标。     

Pretreatment p53 nuclear overexpression as a prognostic marker in superficial bladder cancer treated with Bacillus Calmette-Guérin (BCG)

INTRODUCTION: Altered p53 gene product correlates with the stage and grade of bladder tumor, but its value as a predictor of BCG response has been disappointing. In order to revisit the prognostic value of pretreatment p53 nuclear overexpression for the BCG response, we studied a large cohort of consecutive patients with superficial bladder cancer treated with BCG. METHODS: From 1988 to 2001, 102 patients with a history of multifocal, recurrent, and/or high-risk papillary transitional cell carcinoma or carcinoma in situ, were treated for the first time with BCG. p53 immunostaining was performed on paraffin-embedded tissues using monoclonal antibody DO7 and an automated immunostainer. Special attention was paid to the conditions of tumor fixation. p53 overexpression was defined as more than 20% tumor cells with p53-stained nuclei. RESULTS: Immunostaining was significantly higher for Ta/T1 G3 +/- Cis (p < 0.001), tumoral substage T1b (p = 0.001), grade 3 (p = 0.0001), and Cis (p = 0.002). Times to recurrence, progression and cancer death were shorter among patients with p53 overexpression (p = 0.03; p < 0.0001; p = 0.0003). In multivariate analysis, p53 overexpression was an independent predictor of recurrence (p = 0.0003) [RR = 0.15; 95%CI, 0.06 to 0.42]. CONCLUSION: Pretreatment p53 nuclear overexpression in superficial bladder tumors is associated with a high risk of disease recurrence, progression and cancer death after BCG therapy. Applying antibody DO7 with an automated immunostainer and stringent fixative conditions, p53 nuclear immunostaining yields clinically relevant information and may be a useful tool for selecting patients with superficial bladder cancer who might be resistant to BCG.     

Detection of p53 tumor-suppressor-gene protein in bladder tumors and prostate cancer: possible clinical implications

Summary For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumorsuppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (T_a) tumors to 83.3% of muscle-invasive (T₃/T₄) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G₁ tumors to 75% of G₃ tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T₁) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10). After a median follow-up period of 54 months, 7 of 8 patients for whom more than 20% of cells stained positively for p53 had disease progression as compared with only 1 of 33 patients who were negative for p53 detection (P<0.01; chi-square test). For other urological tumors such as prostate cancer, the results of immunohistochemistry are more difficult to interpret and require definite confirmation on the DNA level.     

Evaluation of p53 nuclear accumulation in low- and high-grade (WHO/ISUP classification) transitional papillary carcinomas of the bladder for tumor recurrence and progression

OBJECTIVES: To evaluate the association of p53 nuclear accumulation with recurrence and progression in transitional cell carcinomas of the bladder and to examine the distribution of p53 in low-grade and high-grade transitional cell carcinomas according to the World Health Organization/International Society of Urological Pathology classification. PATIENTS AND METHODS: Nuclear accumulations of p53 were examined in a total of 99 patients with transitional cell carcinoma between May 1995 and October 1999. The mean age was 64 years. There were 94 (95%) men and 5 (5%) women. Following resection, surgical specimens were examined, and p53 accumulation with a 20% cutoff value was accepted as positive staining. Of the 99 patients, 52 (53%) had histologically superficial bladder tumors, and 47 (47%) had invasive tumors. Data concerning grade, stage, number of recurrences, and disease progression were available for each patient. RESULTS: The median follow-up period was 55 months. 60 of the 99 patients (61%) had p53 overexpression. The difference for p53 overexpression between low-grade and high-grade tumors was significant (p < 0.05). In low- and high-grade tumors, there was no significant relationship for recurrence between p53-positive and p53-negative groups. But there was a statistically significant relationship between progression and histological grade of the tumors. p53 had no significant relationship with tumor recurrences (p > 0.05), but its relationship with progression was statistically significant (p < 0.05). CONCLUSIONS: We did not find a correlation between tumor recurrence and p53 overexpression, but p53 overexpression has a predictive value in determining tumor progression. High-grade tumors had higher p53-positive values than low-grade tumors. This group of patients should be considered for radical therapies on the basis of other prognostic parameters.     

Clinical Significance of Nuclear p53 Protein Accumulation in Bladder Cancer

Objectives: To investigate the correlation of nuclear p53 accumulation with disease outcome in a cohort of patients with transitional cell carcinoma of the bladder. Methods: A total of 90 patients (11 female, 79 male) with transitional cell carcinoma of the bladder were included in this study. Tumour samples from the primary tumour were analysed by immunohistochemistry for nuclear accumulation of p53 protein. Outcome of each patient was recorded and investigated for a possible relation with p53 status. Results: Nuclear p53 deposition was determined in 22 specimens. The nuclear p53 deposition was seen in less than 20% of the nuclei examined in 13 and more than 20% in 9 cases. No stromal staining was observed. Nuclear p53 deposition was present in 15.2% (7/46) of grade 2 tumours, and 34% (15/44) of grade 3 tumours (p=0.037). Stage distribution revealed 15.5% (5/33) positivity in stage pTa, 25.8% (8/31) in pT1 and 34% (9/26) in stage pT2–3 tumours. Tumours with p53 nuclear accumulation had a higher rate of recurrence and progression and shorter survival. Conclusion: Results of the current study indicate p53 as an important factor in determination of biological behaviour of bladder cancer.     

肾移植术后并发泌尿系统肿瘤的相关因素与临床干预

目的:探讨肾移植术后并发泌尿系统肿瘤的相关因素与临床干预措施.方法:报告9例(10次)此种患者的临床资料.9例肾移植术后均行免疫抑制治疗.肿瘤均发生在自体肾、输尿管和膀胱:肾透明细胞癌、肾肉瘤和膀胱腺癌各1例,肾盂输尿管膀胱移行细胞癌6例,其中1例先发生膀胱腺癌后又发生肾盂输尿管移行细胞癌.肿瘤发生于移植术后8～146个月,且8例发生在应用新型免疫抑制剂之后.患者均有服用龙胆泻肝丸或冠心苏合丸史.8例接受了根治性手术,1例未能手术切除.结果:9例随访8～44个月,未能手术切除1例于术后5个月肝转移死亡.1例肉瘤复发后放弃治疗后死亡.1例膀胱肿瘤复发,行膀胱全切腹壁造瘘术,1例腺癌已出现肺和胸膜转移.另5例最后随访时存活良好.结论:肾移植术后并发泌尿系统肿瘤以移行细胞癌为多;可能与服用含马兜铃的中药和应用新型免疫抑制剂有关;根治性手术治疗、减少免疫抑制剂用量和更换免疫抑制剂种类是主要临床干预措施.     

Expression of the cyclin-dependent kinase inhibitor p27 in transitional cell bladder cancers: Is it a good predictor for tumor behavior?

OBJECTIVES: Progression of the cell cycle is regulated by the interactions of cyclins, cyclin dependent kinases (CDKs) and CDK inhibitors (CDKIs). p27 is a member of the universal cyclin-dependent kinase inhibitor family. The level of p27 protein expression decreases during tumor development and progression in some epithelial, lymphoid and endocrine tissues. It has been suggested that p27 is an independent prognostic factor in various human cancers. The prognostic value of p27 protein expression is not completely understood in bladder cancer yet. AIMS: To investigate the immunohistochemical expression of p27 in transitional cell bladder cancers and its relationship with clinicopathological data, proliferating cell nuclear antigen (PCNA) and p53 oncoprotein immunoreactivity. METHODS: The expression of p27 protein was immunohistochemically analyzed in paraffin-embedded specimens of 75 patients with transitional cell carcinoma of the bladder. p27 expression was compared with tumor grade, stage, growth pattern, disease-free survival, progression, PCNA and p53 immunoreactivity. RESULTS: Expression of p27 was not significantly related to clinicopathologic parameters, disease-free survival, progression, PCNA and p53 immunoreactivity. CONCLUSION: The results indicate that p27 is not a good predictor for outcome of transitional cell carcinoma of the bladder.     

p53 in noncancerous bladder mucosa as a marker of disease recurrence in patients with superficial transitional cell carcinoma of the bladder

We investigated the prevalence and clinical relevance of p53 nuclear overexpression in histologically benign bladder mucosa in patients with superficial transitional cell cancer (TCC) of the bladder to look for "premalignant" lesions as the source of tumor recurrence. p53 Accumulation in representative tumor and normal-looking bladder mucosa was studied in 53 patients with Ta and T1 TCC. Histologically normal bladder specimens from 20 prostate cancer patients served as controls. We used a biotin streptavidine-peroxidase system to stain deparaffinized tissue sections with the p53 monoclonal antibody DO7. Specimens from 42 (79%) of the 53 TCC patients stained for p53 in the tumor area. There was no statistically significant difference between pTa and pT1 lesions (pTa, 71.4%; pT1, 87.5%), and staining correlated weakly with tumor grade (G1, 62%; G2, 82%; G3, 100%). Evaluation of histologically normal bladder mucosa showed positive p53 staining in 13 (24.5%) of the 53 patients. Disease recurred in 20 patients. Among them, 12 had positive staining in the normal bladder mucosa. Although p53 expression in tumor areas showed only slight correlation with tumor recurrence (p = 0.043, Cochran-Armitage test), p53 accumulation in healthy bladder mucosa correlated strongly with disease recurrence (p < 0.0001, Fisher's exact test). p53 Overexpression in histologically normal bladder mucosa in patients with TCC might identify premalignant alterations in tumor-surrounding areas. Our data suggest that p53 accumulation in histologically benign bladder mucosa of TCC patients is a possible marker of disease recurrence.     

Expression of cyclooxygenase-2 in normal urothelium, and superficial and advanced transitional cell carcinoma of bladder

PURPOSE: We compared the differential expression of cyclooxygenase-2 in normal bladder tissue, primary bladder transitional cell carcinoma and transitional cell carcinoma metastases to lymph nodes, and determined whether cyclooxygenase-2 expression is associated with molecular alterations commonly found in bladder transitional cell carcinoma and clinical outcomes after radical cystectomy. MATERIALS AND METHODS: Immunohistochemical staining for cyclooxygenase-2, survivin (Novus Biologicals, Littleton, Colorado), p21, p27, pRB, p53, MIB-1, Bax, Bcl-2, cyclin D(1) (Dakotrade mark), cyclin E (Oncogene, Cambridge, Massachusetts) and caspase-3 (Cell Signaling, Beverley, Massachusetts) was performed on archival bladder specimens from 9 subjects who underwent cystectomy for benign causes, 21 patients who underwent transurethral resection and 157 consecutive patients after radical cystectomy, and on 41 positive lymph nodes. RESULTS: Cyclooxygenase-2 was expressed in none of the 9 normal bladder specimens (0%), 52% of transurethral resection specimens, 62% of cystectomy specimens and 80% of lymph nodes involved with transitional cell carcinoma. Cyclooxygenase-2 expression was associated with higher pathological stage, lymphovascular invasion and metastases to lymph nodes (p=0.001, 0.045 and 0.002, respectively). Cyclooxygenase-2 expression was associated with altered expression of p53 (p=0.039), pRB (p=0.025), cyclin D1 (p=0.034) and caspase-3 (p=0.014). On univariate analysis cyclooxygenase-2 expression was associated with an increased risk of disease recurrence and bladder cancer specific mortality (p=0.0189 and 0.0472, respectively). However, on multivariate analysis only pathological stage and metastases to lymph nodes were associated with disease recurrence (p<0.001 and <0.001) and survival (p<0.001 and 0.015, respectively). CONCLUSIONS: Cyclooxygenase-2 is not expressed in normal bladder urothelium. Cyclooxygenase-2 over expression is associated with pathological and molecular features of biologically aggressive disease, suggesting a role for cyclooxygenase-2 in bladder cancer development and invasion.     

wt-p53对小鼠膀胱移行细胞癌生物学影响的研究

目的　探讨膀胱肿瘤的基因治疗途径。　方法　利用Lipofectamine将外源性野生型p5 3基因导入小鼠膀胱移行细胞癌MBST739细胞中 ,并得到表达 ,检测多项生物学指标。　结果　被转染的细胞在体外标准条件下 ,生长增殖率降低。细胞周期分析显示G0 和G1细胞比例明显增高 ,凋亡指数升高 ,细胞生长速度减低 ,代表细胞增殖能力的AgNORs计数下降 ,体内接种致瘤性下降 ,对丝裂霉素和阿霉素的敏感性提高。　结论　增加肿瘤细胞内野生型 p5 3基因表达能抑制恶性肿瘤细胞生长 ,提高肿瘤细胞对化疗药的敏感性