Immunodetection of androgen and estrogen a,b receptors in human urinary bladder cancer

15616 Background: Bladder cancer predominates in males. Loss of androgen receptor (AR) has been associated with invasive and undifferentiated tumors but little is known about the role of hormonal receptors in this type of cancer. Methods: We evaluated samples from 41 nonconsecutive patients treated for bladder transitional cell carcinoma between 2001–2003. Immunohistochemistry was performed using anti-AR and anti-ER a,b antibodies on paraffin-embedded tumors from transurethral resections, nuclear expression was assessed. Western blotting for AR and pAKT were performed in 22 transurethral resections from nonconsecutive bladder cancer patients treated between 2004–2006. Chi-square and U Mann-Witney tests were performed. Results: Immunohistochemistry study: the male/female ratio was 9/1; 61% were noninvasive tumors (pTa, is,1) and 32% were invasive (pT2,3); 22% were G1 and 75% were G2,3. 95% were AR(+), 40% ERa(+) and 94% ERb(+). Significant differences in AR expression were observed between G1 78% and G2,3 tumors 100%, with a high grade tumor prevalence in the AR(+) tumors 81.6% p=0.046. No differences between ERa,b and differentiation were found. G2,3 tumors were predominantly ERb(+). AR was found in 92% noninvasive and in 100% invasive tumors p=0.53. No significant differences were found between invasiveness and ERa,b. Noninvasive tumors showed higher ERa,b expresión (54%, 95% respectively) than invasive tumors (20%, 91% respectively). Western blotting group: 54.5% were primary tumors and 45.5% were recidives. The noninvasive/invasive rate was 59/32%, the G1/G2,3 rate was 4.5/95.5%. 112, 250 and 160 kDa bands were found. AR/pAKT rate was 86.4/100%. 100% of invasive tumors and 86% G2,3 tumors were AR(+). No differences between pAKT, invasiveness, differentiation or AR expression were observed but recidivated tumors had a slight higher median expression level. Conclusions: AR is positively related to tumor grade and might be involved in bladder cancer progression. The profile of AR bands suggest covalent modifications, due to ubiquitin-mediated degradation or to activation mechanisms mediated by SUMO. Nuclear AR and the absence of bands under 90kDa suggest that activated protein is present in bladder cancer. pAKT/AR inhibitors could play a role for bladder cancer therapy. No significant financial relationships to disclose.

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Urinary Bladder Cancer in Egypt: Are There Gender Differences in Its Histopathological Presentation?

Advances in Urology ◽

10.1155/2018/3453808 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Fiorina Kyritsi ◽

Christopher A. Loffredo ◽

Yun-Ling Zheng ◽

George Philips ◽

Sania Amr

Keyword(s):

Gender Differences ◽

Bladder Cancer ◽

Cell Carcinoma ◽

Urinary Bladder Cancer ◽

Tumor Grade ◽

Pelvic Lymphadenectomy ◽

Cancer Type ◽

Bladder Tissue ◽

Primary Bladder ◽

Tissue Specimens

We investigated gender differences in the histopathologic presentation of bladder cancer cases in Egypt, where both urothelial cell carcinoma (UC) and squamous cell carcinoma (SCC) types are highly prevalent. We used logistic regression to estimate the unadjusted (OR) and adjusted odds ratio (AOR) and 95% confidence interval (CI) of the associations between gender and different histopathologic and sociodemographic parameters of 2,186 confirmed cases of primary bladder cancer (1,775 males and 411 females; 784 SCC and 1,402 UC). There were no statistically significant gender differences in tumor grade, stage, mucosal ulcer, or inflammatory cystitis, regardless of the cancer type, but men were less likely than women to have undergone cystectomy with pelvic lymphadenectomy. Having Schistosoma haematobium (SH) ova in the bladder tissue was significantly associated with male gender in the fully adjusted model of either SCC (AOR (95% CI) = 2.12 (1.15–3.89)) or UC cases (3.78 (1.89–7.55)). Compared to females, male cases were significantly older at time of diagnosis and smokers. In Egypt, regardless of the type of bladder cancer (SCC or UC), male more than female cases had evidence of SH infection, but not other histopathologic differences, in bladder tissue specimens.

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Is radical radiotherapy effective for elderly patients with muscle invasive bladder cancer?

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.506 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 506-506 ◽

Cited By ~ 1

Author(s):

James Price ◽

Mayuran Sivanandan ◽

Rania Elmusharaf ◽

Prabir R Chakraborti ◽

Mike Smith-Howell ◽

...

Keyword(s):

Bladder Cancer ◽

Elderly Patients ◽

Systemic Therapy ◽

Transitional Cell ◽

Concurrent Chemotherapy ◽

Invasive Bladder Cancer ◽

Radical Radiotherapy ◽

Muscle Invasive Bladder Cancer ◽

Female Ratio ◽

Muscle Invasive

506 Background: Radical radiotherapy (RT) is a curative option for muscle-invasive bladder cancer (MIBC), and offers the chance of bladder preservation. RT and radical cystectomy have not been compared in an RCT, but landmark trials of RT +/- concurrent systemic therapy have demonstrated outcomes comparable to surgery. In clinical practice, patients are often older and less fit compared to trials, and consequently may not be fit for concurrent chemotherapy which may impact treatment outcomes. Methods: A retrospective review of all patients aged 70 years or older treated with radical RT for MIBC from January 2010 – October 2016. Minimum 12 months follow-up. iSOFT manager for used for clinical data and MOSAIQ for radiotherapy parameters. Statistical analysis performed using Stata version 11.2. Results: 71 patients were identified. Male: female ratio 3:1 and median age 79 (range 71 – 93). Median performance status (PS) 1. 81.7% of patients had pT2 disease or greater, 77.5% of patients underwent TURBT prior to RT and 97.2% had transitional cell-carcinoma histology. 38 patients were treated to 60-64Gy/30-32 fractions and 33 patients to 52.5-55Gy/20 fractions. 6 patients (8.5%) received neoadjuvant chemotherapy and 15 (21.1%) received concurrent chemotherapy. Of the 53 patients who did not receive chemotherapy, all were deemed not suitable. 23 of 71 patients (32.4%) developed a loco-regional relapse, either in the bladder (n = 18), pelvic lymph nodes (n = 4), or on cytology alone (n = 1). 24 patients (33.8%) developed distant metastases, only 7 of these were fit for palliative chemotherapy. The median progression-free survival (PFS) was 17 months (95% C.I. 10 – 34 months). Neoadjuvant and concurrent chemotherapy use was not associated with an increased PFS (p = 0.99 and p = 0.97, log rank). The median overall survival was 18 months (95% C.I. 14 – 27 months). Conclusions: Our data demonstrate RT produces favourable outcomes for elderly patients and reasonably well tolerated without significant toxicities. Use of concurrent systemic therapy did not significantly improve outcomes, but numbers were small.

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EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides

Radiology and Oncology ◽

10.2478/raon-2014-0015 ◽

2015 ◽

Vol 49 (1) ◽

pp. 50-58 ◽

Cited By ~ 25

Author(s):

Jörgen Carlsson ◽

Kenneth Wester ◽

Manuel De La Torre ◽

Per-Uno Malmström ◽

Truls Gårdmark

Keyword(s):

Bladder Cancer ◽

Urinary Bladder ◽

Kinase Inhibitors ◽

Urinary Bladder Cancer ◽

Distant Metastases ◽

Whole Body ◽

Minor Effect ◽

Her2 Expression ◽

Primary Tumors ◽

Egfr Expression

Abstract Background. There is limited effect of tyrosine kinase inhibitors or “naked” antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder cancer and these methods are therefore not routinely used. Targeting radionuclides to the extracellular domain of the receptors is potentially a better possibility. Methods. EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. Results. EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. Conclusions. At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.

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Histone demethylase JMJD1A promotes urinary bladder cancer progression by enhancing glycolysis through coactivation of hypoxia inducible factor 1α

Oncogene ◽

10.1038/onc.2017.13 ◽

2017 ◽

Vol 36 (27) ◽

pp. 3868-3877 ◽

Cited By ~ 32

Author(s):

W Wan ◽

K Peng ◽

M Li ◽

L Qin ◽

Z Tong ◽

...

Keyword(s):

Bladder Cancer ◽

Urinary Bladder ◽

Cancer Progression ◽

Hypoxia Inducible Factor ◽

Urinary Bladder Cancer ◽

Histone Demethylase ◽

Hypoxia Inducible Factor 1Α

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Recurrence rate of superficial bladder cancer with intravesical BCG and mitomycin.

The Professional Medical Journal ◽

10.29309/tpmj/2021.28.06.4968 ◽

2021 ◽

Vol 28 (06) ◽

pp. 854-860

Author(s):

Khalid Hussain ◽

Muhammad Asif ◽

Farooq Malik ◽

Munazza Yasmeen ◽

Maria Tariq ◽

...

Keyword(s):

Bladder Cancer ◽

Mitomycin C ◽

Recurrence Rate ◽

Superficial Bladder Cancer ◽

Controlled Trial ◽

Transitional Cell ◽

Female Ratio ◽

Intravesical Bcg ◽

Group A ◽

Group B

Objective: To compare the recurrence rate of superficial transitional cell carcinoma of urinary bladder using intravesical BCG and Mitomycin-C. Study Design: Randomized Controlled Trial. Setting: Urology Department, Teaching DHQ Hospital, Gujranwala. Period: November 2018, to Sep, 2019. Material & Methods: Was carried out on total 270 patients, admitted with suspicion of urothelial tumors. They were grouped in Group A and B, comprising 135 in each group. Group A received BCG and Group B received Mtiomycin-C intravesically following TUR-BT. Results: Out of 270 patients male to female ratio was 3:1. Age range of patients was between 30 to 70 years with mean of 50.0± 13.1 and 552.3 ± 12.9 years in Group A and B respectively. Recurrence was noted in 05.38% and 15.38% patients in Group A and B respectively. Regarding side effects pyrexia was associated with BCG in 27.40% patients which were self-limited in 26.66% cases however required anti-tuberculosis therapy for six months in 0.74%. Whereas only 06.67% patients receiving Mitomycin had pyrexia. Dysuria occurred in 74% and frequency in 68% patients who received BCG. Whereas Dysuria occurred in 20% and frequency in 36.29% patients who received Mitomycin-C. However genital skin rash was more common (08.14%) in Mitomycin group than BCG. Conclusion: Keeping in mind less recurrence rate and bearable toxicity, it is concluded that BCG is superior to Mitomycin. This study suggests long term follow up is required to establish recurrence in the management of superficial bladder cancer.

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Biomarkers in Bladder Cancer: Present Status and Perspectives

Biomarker Insights ◽

10.1177/117727190700200018 ◽

2007 ◽

Vol 2 ◽

pp. 117727190700200 ◽

Cited By ~ 2

Author(s):

Wun-Jae Kim ◽

Soongang Park ◽

Yong-June Kim

Keyword(s):

Gene Expression ◽

Cancer Research ◽

Bladder Cancer ◽

Cancer Progression ◽

Transitional Cell ◽

Cancer Recurrence ◽

Global Gene Expression ◽

Cancer Therapies ◽

Predictive Capacity ◽

Specificity And Sensitivity

Bladder cancers are a mixture of heterogeneous cell populations, and numerous factors are likely to be involved in dictating their recurrence, progression and the patient's survival. For any candidate prognostic marker to have considerable clinical relevance, it must add some predictive capacity beyond that offered by conventional clinical and pathologic parameters. Here, the current situation in bladder cancer research with respect to identification of suitable prognostic markers is reviewed. A number of individual molecular markers that might predict bladder cancer recurrence and progression have been identified but many are not sufficiently sensitive or specific for the whole spectrum of bladder cancer diseases seen in routine clinical practice. These limitations have led to interest in other molecular parameters that could enable more accurate prognosis for bladder cancer patients. Of particular interest is the epigenetic silencing of tumor suppressor genes. Since the methylation of these genes can correlate with a poor prognosis, the methylation profile may represent a new biomarker that indicates the risk of transitional cell carcinoma development. In addition, bladder cancer research is likely to be revolutionized by high-throughput molecular technologies, which allow rapid and global gene expression analysis of thousands of tumor samples. Initial studies employing these technologies have considerably expanded our ability to classify bladder cancers with respect to their survivability. Future microarray analyses are likely to reveal particular gene expression signatures that predict the likelihood of bladder cancer progression and recurrence, as well as patient's survival and responsiveness to different anti-cancer therapies, with great specificity and sensitivity.

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Prophylaxis of superficial bladder cancer with mitomycin or interferon alfa-2b: results of a multicentric Italian study.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.1.7 ◽

1994 ◽

Vol 12 (1) ◽

pp. 7-13 ◽

Cited By ~ 39

Author(s):

F Boccardo ◽

D Cannata ◽

A Rubagotti ◽

D Guarneri ◽

A Decensi ◽

...

Keyword(s):

Bladder Cancer ◽

Recurrence Rate ◽

Prophylactic Treatment ◽

Superficial Bladder Cancer ◽

Tumor Grade ◽

Interferon Alfa ◽

Primary Tumors ◽

Time To Recurrence ◽

Intravesical Treatment ◽

Ifn Treatment

PURPOSE Interferons have shown a definite activity in the intravesical treatment of residual papillary bladder cancer or carcinoma in situ (CIS). The purpose of the present study was to investigate the efficacy of interferon alfa-2b (IFN) as prophylactic treatment of superficial bladder cancer. PATIENTS AND METHODS Two hundred eighty-seven patients with primary pTa G2, pT1 G1 to G2 superficial bladder cancer, following complete transurethral resection (TUR), were randomly allocated to receive intravesical treatment, either with IFN (50 x 10(6) IU) or mitomycin (MIT-C; 40 mg). Drugs were instilled on a weekly basis for a total of 8 weeks. RESULTS MIT-C was superior to IFN treatment with respect to time to recurrence, relative recurrence rate, recurrence rate per 100 patients per month, and recurrence tumor rate per 100 patients per month. This difference was particularly evident in patients with pTa G2 tumors. After multivariate analysis, the number of primary tumors and tumor grade were the best predictors of recurrence, while allocated treatment had only a moderate effect. Intravesical treatment was well tolerated in both arms. However, more local toxicity was experienced by patients treated with MIT-C. On the other hand, fever occurred significantly more frequently in patients treated with IFN. CONCLUSION IFN was less effective, although locally better tolerated, than MIT-C as prophylactic treatment of primary superficial bladder cancer.

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