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1.

Introduction

Urinary bladder cancer patients who have undergone transurethral resection of bladder tumor (TURBT) are at risk of recurrence. This study aims to correlate the level of bone morphogenetic protein (BMP) expression with urothelial carcinoma invasiveness, TNM stage and time to recurrence after TURBT.

Material and methods

In 33 specimens of healthy transitional epithelium and 42 of urothelial carcinoma, BMP2, BMP4 and BMP7 expression was determined by real-time polymerase chain reaction. Patients who underwent TURBT were followed up for 1 year.

Results

BMP2 and BMP7 were downregulated in infiltrating urothelial carcinoma, the relative expression being 0.76 (p = 0.04) and 0.28 (p = 0.025) respectively, while BMP4 was downregulated in non-invasive tumors. High expression of BMP2 and BMP7 correlated with prolonged time to recurrence (log-rank: p = 0.01 and p = 0.03 respectively).

Conclusions

Low expression of BMP2 and BMP7 is associated with shorter time to recurrence. The BMP expression levels are not indicative of tumor stage.  相似文献   

2.
Background: The Notch signaling pathway is closely related with human organ development and tumorgenisis. Jagged2 is among the most popular topic in Notch studies currently. Recent studies found its vital role in tumor metastasis in breast cancer; however, its expression profile and its prognostic value in urothelial carcinoma of bladder have not been investigated. Methods: Immunohistochemistry was used to detect the expression of Jagged2 in 120 bladder urothelial carcinoma. Moreover, the expression of Jagged2 was analyzed by Western blot in 60 bladder urothelial carcinoma and 20 normal epithelial tissues. MTT assay and flow cytometry and transwell assay were used to examine the proliferative and invasive ability of bladder cancer cells with the treatment of GSIXX (the inhibitor of Jagged2). Prognostic value of Jagged2 expression and its correlation with tumor metastasis and recurrence were evaluated, and the proliferative and invasive ability and cell cycle process of the bladder cancer cells were detected as well. Results: There was a significantly higher Jagged2 expressions in bladder urothelial carcinoma and highly invasive bladder T24 cells than those in bladder normal tissues and the superficial bladder BIU-87 cells. Jagged2 expression was positively correlated with histological grade, p T stage, recurrence, and metastasis. With the increasing concentration of GSIXX, we found that not only the cell proliferation and invasion activity decreased significantly, but also the cell cycle was blocked at G2/M stage. Conclusions: Jagged2 expression status was closely correlated with important histopathologic characteristics (grades and stages) and the recurrence and metastasis of bladder urothelial carcinomas. Furthermore, Jagged2 played an important function on the bladder cancer cells’ proliferation by regulating the cancer cell cycle from G1/S to G2/M and probably promoted the invasion and metastasis of bladder cancer.  相似文献   

3.
About one half of all bladder neoplasms are noninvasive, and in those, the histologic grade is a crucial prognosticator. Few single-center studies have assessed the recurrence, progression, and cancer-related mortality rates of noninvasive high-grade papillary urothelial carcinomas. With this aim, we evaluated the clinicopathologic and outcome features of 85 patients with high-grade papillary urothelial carcinoma. Median age was 68 years, and 80.5% were men. Tumor size ranged from 0.3 to 13.0 cm (median, 1.6 cm). Recurrence was found in 36.5% of the patients, whereas tumor progression, defined as invasion of lamina propria or beyond, was identified in 40% of all cases. When present, lesion reappearance involved mostly 1 to 2 episodes. Metastasis appeared in 20% of the patients, and 15% died of disseminated bladder cancer. All cancer-related deaths occurred in the group of patients with progression, whereas patients with recurrence showed similar outcomes to those with no recurrence. For patients with tumor progression, clinical stage was significantly associated with outcome (P = .002). As for prognosis, tumor size was strongly associated with progression (P < .01). In conclusion, recurrence, progression, and cancer-specific mortality rates were 36.5%, 40%, and 15%, respectively. All the patients who died of cancer had a history of tumor progression. Patients with recurrences showed similar outcomes to those with no recurrence. Tumor size was strongly associated with tumor progression and cancer-specific survival, whereas clinical stage was significantly associated with outcome in the progression group. In light of the high recurrence and progression rates of high-grade papillary urothelial carcinoma, strict clinical surveillance aimed to detect early recurrent lesions, especially in patients with larger tumors, is warranted.  相似文献   

4.
The evaluation of invasion in urothelial carcinomas of the urinary bladder cannot be determined on cytology and can be particularly challenging in biopsy cases with limited sampling. Recent studies of bladder resection specimens suggest that fascin overexpression may be a marker of aggressive urothelial carcinomas and can help facilitate the assessment of invasion. In this study, we evaluated urine cytology and corresponding biopsy specimens with proven invasive urothelial carcinoma for fascin expression by immunohistochemistry. Thirty‐five patients diagnosed with positive urine cytology and biopsy‐proven invasive urothelial carcinoma between January 2003 and February 2009 were identified. We found increased fascin expression in 100% (35/35) of SurePathTM&!trade; urine cytology preparations as well as 100% (35/35) of corresponding biopsy cases with invasive urothelial carcinoma. On urine cytology, cytoplasmic fascin staining was moderate to intense in malignant tumor cell clusters and single cells and not observed in benign urothelial cells. Staining in biopsy cases was generally intense and cytoplasmic and present in both the invasive (100%) and noninvasive (31%) components of the lesion. These findings uphold the association of increased fascin expression in invasive urothelial carcinomas of the urinary bladder. We furthermore demonstrate that fascin staining can be performed successfully on SurePathTM&!trade; urine cytology preparations in which increased fascin expression correlates with invasion on biopsy. While not a definitive marker of invasion, as it is observed in in situ carcinoma, we conclude that the utilization of fascin immunohistochemistry on urine cytology might serve as a useful adjunct in predicting invasiveness in subsequent biopsies. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.  相似文献   

5.
The aim of this study was to evaluate the association between p53, p21, p27 and Rb expression, alone or in combination, with pathological features and clinical outcomes of urothelial carcinoma of the bladder. Immunohistochemical staining for p53, p21, p27 and pRB was performed on tissue microarrays comprising normal urothelium from nine controls, transurethral resection specimens from 74 patients with Ta, Tis and/or T1 bladder urothelial carcinoma, radical cystectomy specimens from 226 consecutive urothelial carcinoma patients, and lymph nodes with tumor invasion from 50 of the 226 cystectomy patients. All nine controls had normal status of biomarkers. The proportion of biomarkers alterations was highest in lymph node metastases. p53, pRB and p27 were associated with pathologic stage, lymphovascular invasion and lymph node metastases (P-values相似文献   

6.
Micropapillary carcinoma is an uncommon variant of urothelial carcinoma with apparent high metastatic potential. The reported cases in the literature were associated with high grade and stage of disease at presentation and a poor prognosis. Micropapillary carcinoma is considered a tumor with an aggressive behavior, even though the morphology may be deceptive. The presence of a micropapillary carcinoma component in bladder biopsies should alert the urologists to the potential of higher stage disease and deep biopsies should be obtained. Two cases of micropapillary carcinoma of the urinary bladder were presented. A 71-year-old woman and a 68-year-old man presented with urinary symptoms. Cystoscopy revealed a papillary tumor on the bladder wall in both cases. Pathologic examination of transurethral resection specimen showed an invasive micropapillary carcinoma; small solid nests lying in small clear spaces that were not stained with antibody CD34. Thus, the lacunar histological pattern did not appear to represent invasion of vascular spaces. Only one case showed an association with urothelial carcinoma. No case showed muscle invasion. No recurrence or metastasis were observed after the initial diagnosis in the two cases.  相似文献   

7.
Few long-term single-center studies have addressed the outcome of patients with papillary urothelial neoplasms of low malignant potential. Our study evaluates the behavior of these tumors occurring as primary urinary bladder lesions. For this purpose, 34 primary in-house cases diagnosed and treated between 1998 and 2008 were identified from our medical records. Upon review, 3 cases were upgraded to noninvasive low-grade urothelial carcinomas and excluded from further evaluation. During follow-up (range, 3-108 months; mean, 42 months), 13 patients developed recurrences; and 9 patients progressed to a noninvasive higher grade lesion (8 to low-grade and 1 to high-grade urothelial carcinomas). None of our patients developed stage progression (>pTa) or died of bladder cancer. Size of the primary tumor was associated with the risk of recurrence (P = .043), whereas the number of episodes of recurrence was associated with the likelihood of grade progression (P = .034). In conclusion, recurrences were observed in 42% of all our patients, with a grade progression rate of 29%. None of our patients developed invasive carcinoma or died as a consequence of their disease. Considering the low but definitive risk of recurrence and grade progression, appropriate clinical follow-up of patients with primary papillary urothelial neoplasm of low malignant potential is warranted.  相似文献   

8.
E-cadherin expression in invasive urothelial carcinoma   总被引:4,自引:0,他引:4  
E-cadherin (E-CD) is a transmembrane glycoprotein involved in intercellular adhesion. A loss or reduction in E-CD expression has been linked to the invasive phenotype of a wide variety of human neoplasms, including bladder tumors. The objective of this study was to compare the E-CD expression at different depths of tumor invasion below the bladder's basement membrane in high- and low-grade urothelial carcinomas to investigate whether deeper tumor invasion and higher-grade invasive urothelial carcinomas are associated with decreased E-CD expression. E-cadherin staining was performed on 29 formalin-fixed, paraffin-embedded sections from high- and low-grade urothelial carcinoma specimens using an automatic immunohistochemical stainer. The sections were divided into three categories according to the depth of invasion below the basement membrane: upper, middle, and lower. The percentage and intensity of E-CD cell membrane staining for the three categories were calculated using a quantitative automated cellular imaging system. The percentage of cells that stained for E-CD was 82.6% +/- 1.4% (mean +/- SD) in the upper layer, 59.6% +/- 2.2% in the middle layer, and 29.4% +/- 2.7% in the lower layer. The intensity of E-CD expression was 64.7 +/- 3.2 units in the upper layer, 43.3 +/- 2.9 units in the middle layer, and 26.1 +/- 3.1 units in the lower layer. There were significant differences between the three layers in both the percentage and intensity of cellular E-CD staining (P<.05). Normal urothelium, high-grade urothelial dysplasia/carcinoma in situ, and superficial noninvasive papillary urothelial carcinoma maintained E-CD expression. However, once malignant cells infiltrated through the basement membrane, E-CD expression decreased. The more poorly differentiated urothelial carcinoma, the deeper the nests, and the smaller the clusters of neoplastic cells within the tumor were, and the more decrease in E-CD expression noted. The degree of decreased E-CD expression was directly proportional to the degree of tumor differentiation and depth of infiltration in invasive urothelial carcinoma. Down-regulation of E-CD may be one of the pathways responsible for tumor differentiation and may promote deeper invasion in urothelial carcinomas.  相似文献   

9.
10.
Bovio I M, Al‐Quran S Z, Rosser C J, Algood C B, Drew P A & Allan R W
(2010) Histopathology 56, 951–956
Smoothelin immunohistochemistry is a useful adjunct for assessing muscularis propria invasion in bladder carcinoma Aims: To prospectively evaluate the utility of smoothelin immunohistochemical expression for the evaluation of muscularis propria (MP) in diagnostic transurethral resection of bladder tumour (TURBT) specimens and cystectomies. Methods and results: Smoothelin immunohistochemistry was performed on a total of 26 TURBT and cystectomy specimens. All but two cases (24/26) demonstrated strong (3+) or moderate (2+) immunoreactivity of the MP with smoothelin. Muscularis mucosae (MM) never displayed strong (3+) reactivity, and in only one case did the MM have moderate (2+) reactivity; in this case the MP had strong (3+) reactivity. MM intensity mirrored the intensity of reactivity of blood vessels in all cases (26/26). Using moderate or strong immunoreactivity as a cut‐off, smoothelin had a sensitivity of 92% for detecting MP and a specificity of 97% for distinguishing between MP and MM. In all unequivocal MP‐invasive and lamina proporia‐invasive cases by haematoxylin and eosin (H&E), smoothelin immunohistochemistry confirmed the original light microscopic diagnosis. In four cases in which there was equivocal MP involvement by H&E, smoothelin helped establish MP invasion. Conclusions: Smoothelin immunohistochemistry has diagnostic utility in the evaluation of MP invasion in urothelial carcinoma. Smoothelin could be used as an adjunct to traditional H&E‐stained light microscopy and may help reduce the number of equivocal diagnoses.  相似文献   

11.
目的:比较2μm激光、钬激光与经尿道膀胱肿瘤切除术(transurethral resection of the bladder tumor,TURBT)治疗非肌层浸润性膀胱癌(non-muscle invasive bladder cancer,NMIBC)的有效性和安全性。方法:2011年6月至2013年6月期间,210例初诊为NMIBC患者被随机分到2μm激光手术组(n=70)、钬激光手术组(n=70)和TURBT手术组(n=70),记录手术时间、相关并发症、术后膀胱冲洗情况、留置导尿时间、住院时间。术后随访2年,定期行表柔比星膀胱灌注化疗和膀胱镜检查,记录膀胱肿瘤复发情况。结果:所有患者均顺利接受相应手术,2μm激光组、钬激光组和TURBT组的平均手术时间和输血率无统计学差异(P>0.05),TURBT组术中闭孔神经反射和膀胱穿孔发生率、术后需要膀胱冲洗病例、留置导尿时间、住院时间均高于2μm激光组与钬激光组,差异有统计学差异(P<0.05),且2μm激光组与钬激光组之间比较无明显差异。术后两年的随访研究中,共有24名患者失访,三组患者肿瘤复发率无统计学差异(P>0.05)。结论:2μm激光和钬激光在治疗NMIBC上优于传统的TURBT,2μm激光与钬激光两者之间临床疗效比较无明显差异。且TURBT、2μm激光和钬激光在术后肿瘤复发方面并无差异,下一步需要更多的病例数和更长的随访时间来验证本研究结果。  相似文献   

12.
BackgroundUrothelial carcinoma of the urinary bladder is the most common malignancy of the urinary system. Patients with low grade papillary urothelial carcinoma (LGPUC) usually have a low risk for tumor recurrence and progression; yet a subset of patients develop recurrence or grade/stage progression to high-grade papillary urothelial carcinoma (HGPUC). The clinicopathological and molecular factors that contribute to this progression are yet to be determined.ObjectivesIn our study, we aimed to assess the incidence and clinicopathological factors associated with tumor recurrence/progression of LGPUC.MethodsUsing a pathological database of surgical specimens from patients who underwent bladder biopsies and/or transurethral resection of bladder tumors (TURBTs) between August 01, 2011, and July 31, 2021, at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed.ResultsOf the total 258 patients included, 157 (60.9 %) had “no recurrence”, 85 (32.9 %) had ≥1 “recurrence of LGPUC”, and 16 (6.2 %) had “grade progression to HGPUC”. The mean follow-up time was 31.5 ± 32 months. Patients with “grade progression” and “recurrence of LGPUC” had larger mean tumor size on initial biopsy and multiple lesions on initial cystoscopy compared to those with “no recurrence.” Interestingly, former smokers had 2.5- and 8.5-times higher risk of recurrence of LGPUC and grade progression, respectively.ConclusionSince the majority of our patients did not develop recurrence, we question whether there is tendency to overclassify the papillomas as LGPUC based on the 2004 WHO/ISUP consensus grading classification.  相似文献   

13.
A proportion of patients under surveillance for recurrent bladder carcinoma with no immediate evidence of bladder tumor recurrence have positive multitarget fluorescence in situ hybridization (FISH; UroVysion, Vysis, Downers Grove, IL) results. The course of these "anticipatory positive" cases and the time to bladder tumor recurrence remains unknown. We followed up 250 patients with urine cytologic results, concurrent multitarget FISH, and cystoscopic examination for recurrent urothelial carcinoma. Of 81 cases (32.4%) with FISH-positive results, tumor recurrence developed in 60 (74.0%). Of 169 (67.6%) FISH-negative cases, recurrent urothelial carcinoma developed in 22 (13.0%). Of 211 patients (84.4%) with negative cystoscopic examination results, 56 (26.5%) had positive FISH results, and in 35 (62.5%) of these patients, recurrent urothelial carcinoma developed. Approximately 27% of patients under bladder carcinoma surveillance without immediate evidence of tumor recurrence will have a positive FISH result, defining the anticipatory positive subset. In about 65% of this anticipatory positive group, recurrent bladder urothelial carcinoma developed within 29 months.  相似文献   

14.
One of the challenging areas in genitourinary pathology is the recognition of early invasion in urothelial neoplasia. Not uncommon, the patterns of invasion into lamina propria are subtle because a desmoplastic response is absent. Tangential sectioning due to inability to orient transurethral resection of bladder tumor specimens, crush and cautery artifacts further compound this problem. This review is presented to familiarize surgical pathologists with the criteria and different patterns of lamina propria invasion by urothelial carcinoma. Problems and pitfalls associated with the recognition of invasion and the clinicopathologic significance of lamina propria invasive urothelial cancer are also discussed.  相似文献   

15.
The nested variant of urothelial carcinoma is a rare urothelial neoplasia which is characterized by relatively bland morphology and early muscle-invasive growth. We report on a 65-year-old male patient with a non-invasive high-grade urothelial lesion (carcinoma in situ and pTa G3). After treatment with BCG an invasive urothelial carcinoma was discovered whereas the carcinoma in situ had disappeared. Examination of the bladder specimen showed a nested-variant urothelial carcinoma. Molecular analyses indicated a de-novo genesis of the invasive urothelial carcinoma.  相似文献   

16.
IntroductionBK polyomavirus is ubiquitous and remains dormant in the urothelial tract, reactivating and replicating in the immunocompromised state especially in the setting of post-renal transplantation where it is believed to be directly oncogenic based on recent reports. Its oncogenic role in the immunocompetent host is controversial. This study aimed to investigate the association of BK polyomavirus in Urothelial Carcinoma.Material and methodsPatients with suspected urothelial carcinoma (UC) admitted under Department of Urology over a period of one year were recruited and transuretheral bladder tumor (TURBT) resection was performed, along with sampling of cystoscopically normal-appearing urothelium away from the tumor. In addition, cystectomy specimens with UC were included, with sampling of grossly normal-appearing urothelium away from the tumor. Immunohistochemistry (IHC) for SV40 T-Antigen and chromogenic in situ hybridization (CISH) using BK polyomavirus specific probe was performed on the paired samples (tumor and normal).ResultsTwenty-three TURBT and 14 cystectomy specimens were assessed. None of the cases showed evidence of BK polyomavirus infection in tumor or in surrounding mucosa by IHC. CISH performed in ten cases were also found to be negative. In comparison, one post-renal transplant urothelial carcinoma in our experience showed diffuse SV40 staining.ConclusionsThis study suggests that BK polyomavirus infection is not associated with urothelial malignancy in the immunocompetent setting unlike in the immunocompromised setting where it should always be investigated for.  相似文献   

17.
The authors designed this study to determine the clinical effectiveness of trimodality treatment, i.e., transurethral resection of a bladder tumor (TURBT) and concurrent chemoradiotherapy (CRT). Twenty patients with a muscle-invasive bladder cancer were treated by TURBT followed by concurrent cisplatin (75 mg/m(2) day), administered on weeks 1 and 4 of radiotherapy. According to residual tumor status after TURBT, patients were classified into patients with a complete TURBT group and incomplete TURBT group. Response to treatment was evaluated by restaging TURBT at 4 weeks after completing CRT (post-CRT). Fifteen patients (75%) achieved complete remission (CR) at restaging; 10 patients (50%) remained continuously free of tumor recurrence. Disease-specific and overall survivals were 51.1% and 38.6% at 5 yr post-CRT, respectively. Of 16 patients in the complete TURBT group, 14 patients (87.5%) achieved CR, which was significantly different from that observed in the incomplete TURBT group, in which only 1 (25%) of 4 patients achieved CR (p=0.032). Five- year disease-specific and overall survivals were 71.6% and 53.5%, respectively. Ten patients (90.9%) maintained their own bladder among the 11 surviving patients. Trimodality treatment was found to be an effective treatment in patients who underwent complete TURBT for a muscle-invasive bladder cancer.  相似文献   

18.
Urothelial carcinoma has numerous histological variants, and these variants may coexist in a single case. Here, we present a case of a 70-year-old man with urothelial carcinoma of the bladder with a maximal diameter of 5 mm that involved micropapillary and plasmacytoid variants, with villoglandular differentiation. The presence of these variants was confirmed by pathological examination of a transurethral resection specimen, and high-grade urothelial carcinoma was found as a minor component. Although this bladder carcinoma was classified as pT1, cystoprostatectomy, urethrectomy, and lymphadenectomy were performed due to the presence of the micropapillary and plasmacytoid variants, which are known to be aggressive. Examination of a surgically resected specimen revealed no carcinoma. A transition between urothelial carcinoma in situ and non-invasive micropapillary carcinoma was found to be a pivot point connecting the diverse morphologies of this bladder carcinoma, from which there existed two pathways. One pathway was from urothelial carcinoma in situ to the plasmacytoid variant through invasive high-grade urothelial carcinoma, and the other was from non-invasive micropapillary carcinoma to urothelial carcinoma with villoglandular differentiation or to the micropapillary variant. This is the 16th reported case of urothelial carcinoma with villoglandular differentiation in the literature. As urothelial carcinoma with villoglandular differentiation is often associated with aggressive variants, as shown in our case, it should be reported whenever encountered in routine pathological practice.  相似文献   

19.
This study is conducted to evaluate prognostic significance of recently introduced WHO (World Health Organization) 1999 grading system for urothelial carcinoma on transurethral resection of urinary bladder tumor (TURBT) specimens reported during the period from 1996 to 2000. Progression free survival estimates were obtained by Kaplan-Meier method on SPSS software with log rank test application. Among 70 cases, progression occurred in 38 patients from which grade I were 3, grade II were 11 and grade III were 24. The mean period from diagnosis to progression was 76.8, 19.2 and 3.5 months for grade I, II, III respectively. The progression free survival rates at one year were 100% for grade I, 42% for grade II and 5% for grade III. (Log rank test: p < 0.001). WHO 1999 grading system can classify urothelial carcinomas into prognostically different groups, which is statistically significant.  相似文献   

20.
We studied 28 cases of lymphoepithelioma-like carcinoma of the bladder, one case in the renal pelvis, and one in the urethra. The mean age of the patients was 67.6 years with 21 (70%) males. Seventeen cases (56.7%) were pure with the remaining mixed with other patterns of carcinoma, including invasive urothelial carcinoma (n=10), invasive adenocarcinoma (n=3), and squamous cell carcinoma (n=2). The surface demonstrated carcinoma in situ (CIS) in six cases, noninvasive high-grade papillary urothelial carcinoma in three cases, and in situ adenocarcinoma in one case. In 19/30 (66%) cases, there was a heavy lymphocytic infiltrate and in the remaining 11/30 (34%) cases a mixed inflammatory infiltrate. None of the 26 cases labeled for EBV-encoded RNA by in situ hybridization. Tumor stages at presentation were: seven cases T1 (23%); 14 cases T2 (47%); seven cases T3 (23%); and two cases T4 (7%). Treatment consisted of radical cystectomy in 13/30 cases (43%); partial cystectomy in 4/30 cases (13%); nephrectomy in one case (3%), and transurethral resection often followed by radiation or chemotherapy in 12/30 (40%) cases. The mean follow up for patients without progression was 31 months. Eight of 27 cases with follow-up (30%) cases had tumor recurrence, with seven patients having metastases. In cases treated with cystectomy, the 5-year actuarial recurrence-free risk was 59% (62 and 57%, for pure and mixed cases, respectively). Lymphoepithelioma-like carcinoma, whether in pure or mixed form, has a similar prognosis to ordinary urothelial carcinoma when treated by cystectomy. Of the three pure cases treated by chemotherapy, two were free of disease at 4 and 65 months and the third had recurrent disease at 17 months. Given the association of lymphoepithelioma-like carcinoma with urothelial carcinoma in 47% of our cases and its propensity for multifocality, partial cystectomy would typically be ill advised for lymphoepithelioma-like carcinoma.  相似文献   

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