Grade Transitional Cell Carcinoma Research Articles

Outcome of Post-resection Intravesical BCG and Mitomycin C Therapy on Non-muscle Invasive High- Grade Transitional Cell Carcinoma of Urinary Bladder

Objective: This study aimed to compare the outcome of postoperative intravesical BCG and Mitomycin C therapy on non-muscle invasive high grade superficial bladder tumor. Methods: This prospective quasi experimental study was carried out among the patients with non-muscle invasive high grade transitional cell carcinoma (TCC) of urinary bladder, who underwent complete transurethral resection of bladder tumor of primary tumor attended at the urology department of DMCH, during March 2017 to August 2019. After pre-operative evaluation and counselling, 70 patients with histologically documented high grade superficial bladder tumor were included and divided in two groups. We instilled intravesical BCG in one group and Mitomycin C (MMC) therapy in other group. The patients were followed up at 3rd ,6th , 9th , 12th and 18th month. Results: The mean age of BCG group was 55.8 years while 60.2years in MMC group with majority between 45 to 65 years (>80%). Sex distribution in both groups were almost equal (p=0.062). There were equal number of TaG3 and T1G3 disease in each group (p=0.809). Local adverse reactions were significant in BCG group (p= 0.016), among them UTI, between two groups, was statistically significant (p=0.039). Incidence of hematuria (p=0.324), voiding frequency (p=0.163) and local rash (P=0.642) had no statistically significant difference. The incidence of post-instillation systemic adverse reactions between two groups were statistically significant (p=0.034). Fever (p=0.028) was significant among them. Intavesical BCG was significantly more effective than MMC in terms of disease recurrence (p=0.047) and progression (p=0.008). Conclusions: We analysed the efficacy and safety of intravesical BCG and MMC in two groups, showing that BCG was more effective in terms of disease recurrence and progression but local and systemic side effects were higher in BCG group. Bangladesh J. Urol. 2021; 24(1): 62-71

Expression of Luteinizing Hormone-Releasing Hormone (LHRH) and Type-I LHRH Receptor in Transitional Cell Carcinoma Type of Human Bladder Cancer

Bladder cancer (BC) is the tenth most frequently detected cancer in both sexes. Type-I luteinizing hormone-releasing hormone (LHRH) receptor (LHRH-R-I) is expressed not only in the pituitary, but also in several types of cancer disease. There are few data about LHRH-R-I expression in human BC. This study aimed to investigate the expression of LHRH and LHRH-R-I in the transitional cell carcinoma (TCC) type of human BC. RNA was extracted from 24 human bladder tumor specimens and three BC cell lines. RT-PCR was performed to detect mRNA for LHRH and LHRH-R-I. The protein of LHRH-R-I was further studied by immunohistochemistry (IHC), ligand competition assay, and Western Blot. PCR products of LHRH were found in 19 of 24 (79%) specimens and mRNA of LHRH-R-I was detected in 20 of 24 specimens (83%). Positive immunostaining for LHRH-R-I with different expression intensity was found in all samples examined, showing negative correlation with TCC grade. Radioligand binding studies also showed the presence of specific LHRH-R-I and high affinity binding of LHRH analogs. The high incidence of LHRH-R in BC suggests that it could serve as a molecular target for therapy of human BC with cytotoxic LHRH analogs or modern powerful antagonistic analogs of LHRH.

Chemopreventive Potential of Myrtenal against Nitrosamine-Initiated, Radiation-Promoted Rat Bladder Carcinogenesis

The present study was undertaken to evaluate the chemopreventive activity of myrtenal, a natural monoterpene, against bladder carcinoma in rats induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and promoted with γ-ionizing radiation (γ-IRR) as well as to assess the involvement of inflammation, apoptosis and oxidative damage in tumor development. Histopathological examination of rat bladder revealed the presence of noninvasive papillary transitional cell carcinoma (Grade 2) in sections from BBN group indicating the credibility of the applied carcinogenesis model. Myrtenal treatment caused improvement in urinary bladder mucosa with cells more likely in Grade 1. Administration of myrtenal to BBN-treated rats exhibited downregulation in the expressions of COX-2, NF-kB and STAT-3 associated with suppression of inflammatory cytokines levels of TNF-α and IL-6 as well as biomarkers of oxidative damage (MDA & NO). In addition, myrtenal treatment caused a significant increase in caspase-3 activity and Bax/Bcl-2 ratio. Data obtained suggested that the anti-inflammatory effect and the induction of apoptosis contributed largely to the beneficial antitumor effects of myrtenal in rats with BBN/γ-IRR-induced bladder carcinoma. Present findings, in addition to benefits described in other pathologies, indicated myrtenal as a potential adjuvant natural compound for the prevention of tumor progression of bladder cancer.

Adaptive genetic algorithms combined with high sensitivity single cell-based technology derived urine-based score to differentiate between high-grade and low-grade transitional cell carcinoma of the bladder.

572 Background: We previously showed that adaptive genetic algorithms (AGA), in combination with single-cell flow cytometry technology, can be used to develop a noninvasive urine-based score to detect bladder cancer with high accuracy. Our aim in this analysis was to investigate if that same score can differentiate between high grade (HG) and low grade (LG) transitional cell carcinoma of the bladder (BC). Methods: We collected urine samples from cystoscopy confirmed HG and LG superficial bladder cancer patients and healthy donors in an optimized urine collection media. We then examined these samples using an assay developed from AGA in combination with single-cell flow cytometry technology. Results: We examined 50 BC and 15 healthy donor urine samples. Patients were majorly White (59.2%), males (61.2%), and had HG BC (66.7%). AGA derived score of 1.1 differentiated between BCa and healthy patients with high precision (AUC 0.92). The median score was 2.8 for LG BC and 6 for LG BC. Mann-Whitney Rank Sum Test indicated that the difference between the median score of HG and LG BC was significant at P value = 0.003. The score performed well independent of patients’ sex or smoking history. Conclusions: Using single-cell technology and machine learning, we developed a new urine-based score that can potentially differentiate between HG and LG bladder cancer. Future studies are planned to validate this score.

Expression of FOXA1 and GATA3 correlates with invasivity and pathological stage a grade of primary transitional cell carcinoma of the bladder

Bladder cancer is the fifth most common malignancy in men and the second most commonly diagnosed urogenital tumor. Approximately 400,000 new patients with this disease occur each year in the world. Incidence rates are 4 times higher in men than in women. Diagnosis is based on cystoskopy, radiological examination and histological examination. Histological evaluation provides definitive diagnosis and also provides information about pathological stage and grade. Recently, methods of molecular biology are used to predict biological behavior an prognosis more precisely. In this study we evaluated 73 patients with primary transitional cell carcinoma (TCC) of urinary bladder (39 patients pTa and 34 pT1 TCC). Total RNA was extracted from bladder tissue samples using GeneJET RNA Purification Kit (Thermo Scientific, USA) according to the manufacturer's recommendations. First‐strand cDNA was synthesized from total RNA with Maxima First Strand cDNA Synthesis Kit for RT‐qPCR (Thermo Scientific, USA). Reaction was performed according to protocol recommended by manufacturer. Obtained cDNA was used as a template for quantitative PCR to determine the expression level of selected genes (TP53, BCL2, FOXA1 and GATA3). The PCR reactions were performed on Eco Real‐Time PCR System (Illumina, USA). Expression of all analyzed genes was normalized to housekeeping gene, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH). Obtained results showed that expression levels of TP53 and BCL2 showed no significant differences in both groups. Conversely, significantly lower expression of FOXA1 and GATA3 were detected in pT1 TCC when compared to pTa TCC. Moreover, significantly higher expression of FOXA1 and GATA3 was detected in high grade TCC when compared to low grade tumors. Based on our findings, expression of FOXA1 and GATA3 correlates with invasivity and pathological stage a grade of primary bladder TCC, and may be used for further research in prospective studies.Support or Funding InformationVEGA No. 1/0207/16.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Correlation of epidermal growth factor receptor score with prognostic variables in transitional cell carcinoma of urinary bladder among north-eastern Indian population

Background: Epidermal growth factor receptor (EGFR) has demonstrated over expression in bladder tumours and correlation with stage and grade of tumours. The aim of present study was to find the relation between score of the EGFR in Transitional Cell Carcinoma (TCC) of bladder and its various prognostic variables.Methods: This is a retrospective study conducted in Dept of Urology, Gauhati Medical College Hospital between Dec 2016 and July 2017. Forty cases of TCC bladder that were operated either by TURBT or radical cystectomy have been taken. However, patients with CKD, pre-existing systemic disease and UTI were excluded from the study. Presence of EGFR and its score were analysed. The rating was done as 0 (non-immunoreactive), 1+ (weak), 2+ (moderate) and 3+ (strong). The correlation between EGFR score and the various factors like age, sex, stage, size of tumour, presence of CIS, tumour grade, muscle invasion, number of tumours and type of stalk were evaluated statistically using chi square tests.Results: Average age is 59.825 years and male to female ratio is 5.6:1. EGFR score is not significantly related with age, sex, stage of disease, muscle invasiveness or number of tumours whereas size of tumour, presence of CIS changes, grade of TCC and type of tumour stalk bears statistically significant relation with EGFR score.Conclusions: Studies have shown EGFR positivity to be associated with high tumour stage, tumour progression, and poor clinical outcome. Authors have found size >3cm, CIS changes, high grade tumours and broad-based stalks to be significantly associated with higher EGFR scores among patients with TCC of bladder.

Role of coagulation factors in urological malignancy: A prospective, controlled study on prostate, renal and bladder cancer.

To study the behavior of specific coagulation factors in different types of non-metastatic urological cancers, and to identify their possible role as diagnostic and prognostic markers. This was a prospective controlled study, which included three cancer patient groups and a control group of healthy individuals. The cancer subgroups consisted of renal (n = 44), prostate (n = 56) and bladder cancer (n = 47). We excluded patients receiving anticoagulant therapy, or with significant comorbidity. In all patients, certain coagulation parameters were measured (prothrombin time, international normalized ratio, partial thromboplastin time, D-dimers, fibrinogen, F1 + 2, thrombin-antithrombin complex). Statistical analysis was carried out to explore the association of hemostasis markers with tumor-nodes-metastasis stage, Gleason score, transitional cell carcinoma grade, Fuhrman grade and prostate-specific antigen. Our final sample consisted in 58 control patients and 147 patients with urological cancer. We found specific patterns of increased coagulation factors in the different cancers that were statistically significant. Renal cancer showed increased levels of D-dimers, partial thromboplastin time and fibrinogen. D-dimers and fibrinogen were increased in prostate cancer; whereas in bladder cancer, only fibrinogen was elevated. Correlations were found between certain factors and tumor stage and grading, with D-dimers being independently associated with higher tumor grade. Thrombin-antithrombin complex was associated with Gleason score. Furthermore, D-dimers, fibrinogen and F1 + 2 were associated with higher tumor stages (II-IV). The coagulation pathway seems to be activated in urological malignancies. Specific panels of coagulation factors might play a role as screening or prognostic tools in earlier stages of renal, prostate and bladder cancer. Further research should also focus on their role in the association of cancer with thromboembolic events.

ETS-1 oncoprotein expression is decreased in aggressive papillary transitional cell carcinoma of the urinary bladder: An immunohistochemical study

IntroductionETS-1 proto-oncogene is a transcription factor that plays multiple roles in the process of oncogenesis and helps in the process of tumor invasion. ETS-1 oncoprotein correlation with high grade and invasive tumors is controversial; as it is found to be upregulated with some tumors and down regulated with others. Expression of ETS-1 in urinary bladder carcinoma (UBC) and its correlation with tumor differentiation and invasiveness are still under-investigated. So far, there is no reliable prognostic marker has been proved for detection of the tumor progression and recurrence. ObjectivesTo analyze the correlation between ETS-1 oncoprotein immunohistochemical expression and the different stages and grades of the primary papillary transitional cell carcinoma of the urinary bladder. Patients and methodsThis is a retrospective cross sectional study that included archival material from 150 cancer cases and 24 control biopsies. ResultsThere was a decreased ETS-1 oncoprotein expression with increasing stage and grade of the tumor with a highly significant statistical correlation (P=0.001). With the quantitative assessment of the immunohistochemical results and using ROC (receiver operating characteristics) curve, cut-off values were found, that were associated with high grade and muscle invasive tumors (≤30% and ≤20%, respectively). ConclusionETS-1 oncoprotein is down regulated with high grade and highly invasive urinary bladder papillary transitional cell carcinomas. This oncoprotein may be used as an independent prognostic marker to predict the aggressive papillary transitional carcinomas with high invasive potential. More studies are needed to confirm our results.

Ovarian Brenner Tumors Revisited: Do We Have Space for Malignant Tumorsvand Methanol

Summary We present a case of a 75-year-old female who underwent a total abdominal hysterectomy with bilateral salpingooophorectomy for an ovarian tumor. Hematoxylin-eosin- stained slides from tumor specimen revealed 1) focci of benign Brenner tumor; 2) mucinous cysts and 3) intracystic papillary projections resembling low-grade papillary transitional cell carcinoma (Grade 1-2) with squamous differentiation and comedo-type necrosis; 4) focal areas resembling noninvasive papillary transitional cell carcinoma Grade 3. Immunohistochemical investigation with a panel of antibodies (p63, p53, Ki-67, Wilms Tumor 1 - WT1, pi 6) was initiated. Areas resembling urothelial carcinoma showed diffuse nuclear positive reaction for p63 and wild-type expression of p53. Ki-67-nuclear positivity varied from less than 5% up to 30% in areas resembling high-grade urothelial carcinoma. WT1 expression was not seen. Weak but still exceeding background staining was observed in predominantly cytoplasmic fashion with few scattered positive nuclei in transitional cell nest of the benign component. No reactivity, however, was seen within the proliferative component. The histopathological diagnosis was a borderline/atypical proliferative Brenner tumor. The patient has been regularly followed up and is at present disease-free 5 years after diagnosis. In this paper, the authors describe the morphological characteristics of Brenner tumors and address some debatable issues in the light of recent immunohistochemical and molecular studies.

Long noncoding RNA HOTAIR is a prognostic biomarker and inhibits chemosensitivity to doxorubicin in bladder transitional cell carcinoma.

In this study, whether HOTAIR is a prognostic biomarker will be detected, and its regulative effects of chemosensitivity to doxorubicin in TCC cells will be examined. The expression of HOTAIR was detected by quantitative real-time PCR. Overall survival rate was calculated by Kaplan-Meier method with the log-rank test for comparisons. MTT assay was used to detect cell proliferation ability and chemosensitivity. Dual-color flow cytometric method was used to detect cell apoptosis. HOTAIR was up-regulated in bladder transitional cell carcinoma (TCC) tissues and cell lines compared with normal bladder transitional cell (NBTC) tissues and bladder epithelial immortalized SV-HUC-1 cells, and its expression level had positive correlation with histological grades of TCC. Moreover, HOTAIR was an independent prognostic biomarker of overall survival for TCC patients. The expression and silence vector for HOTAIR were transfected into T24 and J82 cells to up-regulate and silence the HOTAIR expression, respectively. In T24 and J82 cells, HOTAIR over-expression promoted cell proliferation and inhibited chemosensitivity to doxorubicin and cell apoptosis induced by doxorubicin; silence of HOTAIR showed opposite regulative effects. In summary, lncRNA HOTAIR was an independent prognostic biomarker of overall survival in TCC patients and could regulate chemosensitivity to doxorubicin of human TCC cells. HOTAIR might provide a new potential therapeutic target and stratagem for TCC.

Sensitivity and specificity of urinary hyaluronic acid and hyaluronidase in detection of bladder transitional cell carcinoma.

To the assess sensitivity and specificity of urinary levels of hyaluronic acid (HA) and hyaluronidase (HAase) as an individual or a combined test to diagnose bladder transitional cell carcinoma (TCC). One hundred and ninety-four urine specimens were collected from individuals between July 2007 and March 2008. The urinary level of hyaluronic acid (HA) was measured by Enzyme-linked immunosorbent assay. Thereafter, the urinary levels of HA and HAase were normalized to urinary creatinine level and expressed as ng/mg and μ/mg. Eighty percent of patients with bladder cancer had urinary HA level < 500 ng/mg, and 90% of controls showed HA level < 500 ng/mg (P < .001). The mean urinary levels of HA in controls did not vary significantly (P < .05), whereas they significantly increased (2.5 to 6.5 folds) in all grades of TCC. More than 80% of patients with grades 2 and 3 TCC had urinary HAase level < 10 μ/mg and over 80% of controls showed HAase level < 10 μ/mg (P < .05). Hyaluronidase levels increased in patients with grades 2 and 3 bladder TCC. Measurement of urinary levels of HA and HAase (with 89% sensitivity and 83% specificity) appears to be a highly accurate and non-invasive method for detecting bladder TCC and evaluating its grade.

Study of Urothelial Neoplasm in Central India With Reference To WHO/ISUP Grading

Introduction: Urothelial carcinoma is the most common bladder cancer, is often described as a polyclonal field change defect with frequent recurrence due to heightened potential for malignant transformation. Urothelial neoplasm runs the gamut from small benign neoplasm that may never recur to tumors of lower indeterminate malignant potential to lesions that invade the bladder wall and metastasize frequently. Hence histologic grading of these tumors to predict behavior has been subject of great debate as there is poor inter - observer reproducibility and no uniformity. Material and Methods: The present study was carried out in the Department of Pathology, L.N. Medical College, Bhopal, India. It was both a prospective and a retrospective study of 80 patients whose urinary bladder biopsy were studied. Result: 80 cases reported out of which 20 were transitional papilloma, 52 were cases of ransitional cell carcinoma and 8 cases were of squamous cell carcinoma. The majority of tumours are present in age group of 50-80 years. Discussion: Although World Health Organization classification system is most commonly used grading system but lack of detailed histological criteria motivated WHO and ISUP to publish a consensus classification for urothelial neoplasm of urinary bladder. The majority of the cases in this study belonged to the histologic grades of papillary carcinoma of low grade which corresponds to the WHO classification of transitional cell carcinoma grade II.

Comparison of Urinary and Serum CA 19-9 as Markers of Early Stage Urothelial Carcinoma

Although the glycoprotein group tumor marker CA 19-9 has been detected in both serum and urine of bladder cancer patients, information about their comparative role in screening of low grade transitional cell carcinoma (LGTCC) and high grade transitional cell carcinoma (HGTCC) is rare. In this study we measured both the urinary and serum levels of CA 19-9 in 35 LGTCC and 20 HGTCC patients by ELISA and determined the cut off value of both urinary and serum CA 19-9 levels by receiver operator characteristic curve (ROC) for both patient groups. Odds ratio (OR) for CA 19-9 was analyzed with its range at 95% confidence interval to analyze the role of this tumor marker as a screening parameter for both of these cancer types. For urinary CA 19-9 the OR was 20.16 with an interval of 4.91-82.71 whereas for the serum CA 19-9 it was 7.5 with an interval of 2.28-24.62. From these data we suggest that urinary CA 19-9 is a better screening parameter with optimum sensitivity and specificity than its serum counterpart for diagnosis of low grade and early stages of transitional cell carcinoma of urinary bladder. Furthermore, it can be suggested that urinary CA 19-9 can be used as better prognostic marker for LGTCC than its serum counterpart.

Association of prostate stem cell antigen and the recurrence of bladder tumor after operation

Objective To investigate the expression of prostate stem cell antigen (PSCA) in transitional cell carcinoma (TCC) of the urinary bladder and the implication.Methods The expression of PSCA in 50 cases of TCC of the urinary bladder was detected by using the PV immunohistochermical method,including 14 cases of recrudescent group and 36 cases of unrecrudescent group.The correlation of PSCA expression with postoperational recurrence and clinicopathological features of TCC was analyzed.Results The positive expression rate of PSCA in G1,G2,G3 of TCC was 94.0％ (14/15),79.0％ (11/14),85.7％ (6/7),and 57.0％ (8/14) in recrudescent patients.Ther was significant difference in the PSCA expression level between recrudescent tissues (18.32 ± 1.76) and unrecrudescent tissues (23.09 ± 1.50) (P ＜ 0.05).The PSCA expression was negatively correlated with the pathological grade of TCC (r =-0.458,P ＜ 0.05).Conclusion These findings suggest that the PSCA expression could be used as a valuable prognostic marker for recurrence of bladder cancer after operation. Key words: Protate stem cell antigen; Bladder carcinoma; Recurrence

THE SIGNIFICANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR AND SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE CYTOLOGY OF PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER.

To assess whether epidermal growth factor receptor (EGFR) and survivin immunostaining of tumour cells in urinary cytology and tissue of patients with bladder cancer has a prognostic significance. Prospective study Department of Surgery (Division of Urology), Mubarak Al-Kabeer Teaching Hospital and Faculty of Medicine, Kuwait University, Kuwait Urine cytology smears obtainedpriorto cystoscopy in patients with transitional cell carcinoma (TCC) of the bladder were immunostained for EGFR and survivin. Bladder cancer tissue resected at surgery was also immunostained for EGFR and survivin expression. Tissue expression of EGFR and survivin in TCC of the bladder was compared to their expression in urine cytology and relationship to tumour grade and stage. 178 patients were studied (43 newly diagnosed bladder cancer, 58 with recurrent TCC and 77 in disease remission). Twenty five patients with normal urothelium served as controls. The mean sensitivity of urine cytology, tissue survivin immunohistochemistry (IHC) and tissue EGFR IHC was 30.5%, 62% and 59% respectively. The corresponding mean specificity was 95%, 79% and 38% respectively. For grades 1, 2 and 3 bladder tumors, tissue expression positivity for EGFR was 47.8%, 92.9%, 100% and for tissue survivin it was 27.8%, 18.2% and 33.3% respectively. For grades 1, 2 and 3 bladder tumors, urine expression positivity for EGFR was 35.7%, 40% and 67.7% and for urine survivin it was 8.3%, 42.9% and 33.3% respectively. Positive EGFR immunostaining of urine cytology specimen or tumour tissue increases with histological grade of TCC of the bladder. Survivin expression is less consistent in both urine cytology specimen and tissue samples. EGFR immunostaining may provide a useful tool in the grading of bladder TCC and aid in the selection of patients that may benefit from administration of EGFR inhibitors.

1600 IS SMOKING ASSOCIATED WITH HIGHER STAGE AND GRADE BLADDER CANCER? PROSPECTIVE LONG-TERM FOLLOW-UP STUDY

You have accessJournal of UrologyBladder Cancer: Invasive II1 Apr 20121600 IS SMOKING ASSOCIATED WITH HIGHER STAGE AND GRADE BLADDER CANCER? PROSPECTIVE LONG-TERM FOLLOW-UP STUDY Said Mishriki, Bhavan Rai, Bhaskar Somani, and Omar Aboumarzouk Said MishrikiSaid Mishriki Aberdeen, United Kingdom More articles by this author , Bhavan RaiBhavan Rai Aberdeen, United Kingdom More articles by this author , Bhaskar SomaniBhaskar Somani Aberdeen, United Kingdom More articles by this author , and Omar AboumarzoukOmar Aboumarzouk Aberdeen, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1373AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Smoking is a well documented risk factor for developing bladder cancer. Stage and grade are well known significant prognostic factors. Muscle invasive disease and higher grades carry poor prognosis. This prospective study assesses the association between smoking and developing higher stages and grades of transitional cell carcinoma (TCC). METHODS 189 patients with histologically proven TCC were prospectively identified and followed up between 2000 and 2005. Patients were grouped according to their smoking history. Smokers (current and former) and non smokers were grouped separately. The pathological stage and grade of the disease as documented in the pathology laboratory reports was evaluated for smokers and non-smokers. Five patients with carcinoma in situ (CIS) were analysed separately. RESULTS 128 (67.7%) smokers and 61 (32.3%) non-smokers were identified.A higher percentage of muscle invasive disease was associated with smoking (Table 1). Smoking and Bladder Cancer Grade Stage Ta(%) T1(%) T2(%) T3(%) T4(%) Smoker 70(54.7) 26(20.3) 23(18.0) 5(3.9) 4(3.1) Non-Smoker 36(59.0) 18(29.5) 7(11.5) 0(0) 0(0) This was statistically significant. Fisher's exact test p=0.035. This was also statistically significant. Chi-Square p <0.0001 CONCLUSIONS To our knowledge, this is the first study that links smoking with stage and grade of TCC of the bladder. In addition to predisposing to TCC of the bladder, smoking seems to significantly increase the risk of developing higher stage and grade. Smoking and Bladder Cancer Grade Grade G1(%) G2(%) G3(%) CIS Smoker 24(18.8) 55(43.0) 49(37.7) 2 Non-Smoker 34(55.7) 17(27.9) 10(16.4) 3 © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e647-e648 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Said Mishriki Aberdeen, United Kingdom More articles by this author Bhavan Rai Aberdeen, United Kingdom More articles by this author Bhaskar Somani Aberdeen, United Kingdom More articles by this author Omar Aboumarzouk Aberdeen, United Kingdom More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Urinary Survivin mRNA Expression and Urinary Nuclear Matrix Protein 22 BladderChek® and Urine Cytology in the Detection of Transitional Cell Carcinoma of the Bladder

Objective: To compare the diagnostic performance of urine cytology (UC), survivin mRNA expression, and the NMP22 BladderChek® (NMP22BC) test for the detection, grading and staging of transitional cell carcinoma (TCC) of the bladder. Materials and Methods: Voided urine samples collected from 25 healthy controls and 80 patients diagnosed with TCC of the bladder were subjected to UC, the NMP22BC test and reverse-transcription real-time PCR for survivin mRNA expression. Results: Survivin mRNA expression showed the highest sensitivity (87.5%) followed by the NMP22BC test (61.3%) while UC exhibited the lowest sensitivity (40%). All three urine markers had a similar specificity of 96% (95% CI 80.5–99.3%). Survivin mRNA expression was the only urine marker that showed a significant difference in relation to tumour histological grade (χ² 8.5, p = 0.015). None of the three urine markers was significantly related to tumour pathological stages. Conclusion: The diagnostic sensitivity of urinary survivin mRNA expression was superior to that of UC and the NMP22BC test and correlates with tumour pathological grade but not stage.

The Relationship between Mast Cell Density and Tumour Grade in Transitional Cell Carcinoma of the Bladder

This study investigated the relationship between mast cell numbers and the grade of bladder transitional cell carcinoma (TCC). Bladder TCC biopsies were obtained via transurethral resection and 45 stage T1 specimens were included in the study. Specimens were sorted into two groups, low grade (grade I) and high grade (grades II and III). Samples were stained using haematoxylin and eosin, toluidine blue and immunohistochemical staining for tryptase. Mast cells were examined by light microscopy and cell density was recorded. Mast cell density was significantly higher in high-grade TCC than low-grade TCC. There was also a significant relationship between the number of mast cells identified using toluidine blue staining or immunohistochemical staining for tryptase. Detailed studies of mast cell function will enable the development of more effective antitumour therapies via mast cell manipulation.

Correlation of Pathological and Cytological-Cytometric Grading of Transitional Cell Carcinoma of the Urinary Tract

Introduction: Cystoscopy and cytology are standard procedures for diagnosis and follow-up of patients with bladder cancer. Urinary cytodiagnosis is a descriptive method for tumor characterization. We correlated histopathologic diagnosis of noninvasive urothelial carcinomas with cytological evaluation and, furthermore, we validated cytology by cytometric analysis. Patients and Methods: 94 patients with a history of bladder cancer were included in the study. 25 patients were negative for tumors, 22 showed pTa G1 carcinomas, 25 had pTaG2 and 22 patients had G3 carcinomas. All patients underwent cytological and cytometric evaluation. Nuclear diameter and circumference were measured for 15 representative nuclei per specimen. Statistical evaluation was performed using Graph Pad Software. Results: Cytology showed excellent tumor detection for G2 and G3 carcinomas, with a sensitivity of 100% combined with a specificity of 100%. Using cytometry, we can significantly distinguish between unsuspicious patients and G1 carcinomas on the one hand and high-grade carcinomas on the other. Furthermore, in 6 of 25 patients (24%) with noninvasive G2 carcinomas, but G3 cytological evaluation, tumor progression occurred. Conclusions: Urinary cytology is an excellent instrument for detection of clinically relevant high-grade bladder cancer. Descriptive alterations of the cytopathology can be validated by objective data using cytometric analysis.

Overexpression of BDNF and TrkB in human bladder cancer specimens

BDNF (brain-derived neurotrophic factor) and TrkB (tropomyosin receptor kinase B) are expressed in several tumor types. However, the existence of BDNF and TrkB in human bladder cancer, especially transitional cell carcinoma (TCC), has not been established. In this study, commercial TCC tissue arrays were used. Slides of paraffin-fixed human bladder tissues included all grades of TCC (13, 30 and 22 tissue samples in grade I, II and III, respectively), superficial and invasive TCC (31 and 34 tissue samples, respectively), paired malignancy-uninvolved urothelium (35 tissue samples) and normal urothelial tissues (12 tissue samples). The intensities of BDNF and TrkB immunostaining were graded as background, mild and strong (score as 0, 1 and 2, respectively). The results showed significantly overexpressed BDNF and TrkB in TCC samples compared to normal urothelium. According to grade assignment of TCC samples, BDNF in grade III and TrkB in grade I and III appeared to be overexpressed. BDNF and TrkB were overexpressed in superficial TCC samples according to staging classification. The score between the paired TCC and its uninvolved urothelium was not statistically different. In conclusion, the existence of overexpressed BDNF and TrkB in human TCC has been demonstrated in our study. A strategy involving BDNF/TrkB blockade may be a new hope for TCC target therapy.