Cases Of Urothelial Carcinoma Research Articles

Immunohistochemical Expression of Claudin-1 and Claudin-4 in Urothelial Carcinoma of the Urinary Bladder.

In Egypt, bladder cancer occupies the second rankamong reported cancers in men. Claudins are tight junctions that have a critical role in tumor pathogenesis, invasion, progression, and metastasis and currentlyare a focus of interest for targeting therapies. We aimed to evaluatethe immunohistochemical expression of Claudin-1 and Claudin-4 in urinary bladder urothelial carcinoma and investigate the relationshipbetweenthe expressed Claudins with differentclinicopathological parameters. Claudin-1 and Claudin-4 immunohistochemical expression was studied in 62 cases of urinary bladder urothelial carcinomas. The cases were classified into two categories; low and high Claudin-1 and Claudin-4 expression. High Claudin-1 expression was detected in67.7% of the studied urothelial carcinomas while 32.3% showed low expression. Claudin-1 expression was reduced significantly with high tumor grade, non-papillary tumors, muscle invasion, schistosomal infestation, and perineural invasion (p-value < 0.05). Claudin-4 high expression was detected in 82.3% of our cases while low expression was detected in 17.7%. Claudin-4 reduced expression was significantly associated with non-papillary tumors, muscle invasion, advanced T stages, and associated lympho-vascular emboli (P-value < 0.05). According to the results ofthe present study, the reduced expressions of Claudin-1 and Claudin-4 provide clues concerning the progression of urothelial carcinoma. Consequently, it is thought that Claudin-1 and Claudin-4 could help to differentiatelow-grade from high-grade and muscle-invasive from non-muscle-invasive urothelial carcinomas. In addition, it can be introduced as a possible therapeutic target.

Do Fibroblast Growth Factor Receptor (FGFR) 2 and 3 Proteins Play a Role in Prognosis of Invasive Urothelial Bladder Carcinoma?

Bladder carcinoma ranks second in prevalence among males in Egypt. As a family of tyrosine kinases, fibroblast growth factor receptor (FGFR) dysregulation has been linked to some malignancies in humans. The aim of this study is to analyze the clinicopathological data of patients while investigating FGFR2 and FGFR3 immunohistochemical expression in invasive urothelial bladder carcinoma. This retrospective cross-sectional study included 60 invasive urothelial carcinoma (UC) cases in the Pathology department, Faculty of Medicine, Menoufia University, from 2009 to 2020. All biopsies were stained for FGFR2 and FGFR3 antibodies. Complete clinical data were available for 44 patients treated and followed in clinical oncology and nuclear medicine departments. Advanced stage and high grade are significantly correlated with FGFR2 positivity (P=0.048 and 0.044, respectively). Cases presented with Perineural invasion showed a higher percentage of FGFR2 (P=0.023). There is a significant indirect linear correlation between FGFR3 expression and lymph node positivity (r= -0.265, P=0.041). A high FGFR2 expression could be associated with poor prognostic parameters, while high FGFR3 expression would be associated with good prognostic parameters. These findings might highlight the importance of FGFR-targeted therapy as a FGFR2 antagonist and FGFR3 agonist for the treatment of urothelial carcinoma patients.

Immunohistochemical Expression of HER2/Neu in Urothelial Carcinoma: A Cross-sectional Study

Introduction: Urothelial Carcinoma (UC) is a disease with significant mortality, estimated to be the ninth most common cause of cancer worldwide and the thirteenth most common cause of death from cancer. It has a significant impact on public health and will continue to do so due to the high prevalence of smoking. To combat the growth of urothelial cancer, awareness regarding primary prevention must be underscored, and smoking cessation programs need to be encouraged and supported. Aim: The aim of this study is to determine the expression of Human Epidermal Receptor 2 (HER2)/neu in UC and its association with age, size, type, grade, and invasion of the tumour. Materials and Methods: This cross-sectional study was conducted at the Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research (a tertiary care centre) in Amritsar, Punjab, India, from January 1st, 2019, to December 31st, 2020. Fifty histopathologically proven cases of UC were examined. HER2/neu expression was studied using immunohistochemistry, and its correlation with age, size, type, grade, and invasion was analysed. The findings of the study were statistically analysed using Statistical Package for the Social Sciences (SPSS) software version 21.0, a statistical program for Microsoft Windows. Results: A total of 50 patients were analysed for the study (40 males and 10 females, with a mean age of 60.4 years at presentation). Nineteen cases were low-grade, and 31 cases were high-grade, with high-grade cases being more invasive. Thirteen cases showed HER2/neu expression, of which 11 were high-grade, indicating a statistically significant relationship between grade and HER2/neu expression. Similarly, expression was higher in cases with lamina propria and muscularis propria invasion. Out of the 34 cases showing lamina propria invasion, 10 cases were positive for HER2/neu expression, constituting 29.4%. Among the 42 cases involving muscularis propria in the biopsy, 16 cases showed muscularis propria invasion by the tumour, with four cases (25%) being positive for HER2/neu expression. Conclusion: The expression of HER2/neu increases with grade and shows more positive expression in high-grade invasive tumours involving lamina propria or muscularis propria. This indicates that HER2/neu protein overexpression is associated with aggressive disease and serves as a negative prognostic marker. Targeted therapy against HER2/neu may prove to be beneficial in such patients.

Evaluation of GATA3 and p53 Expression in Urothelial Carcinoma and their Association with Clinicopathological Parameters: A Cross-sectional Study

Introduction: Bladder cancer is the tenth most common cancer worldwide, with 90% of bladder cancers are Urothelial Carcinoma (UC). In India, its incidence is 1.6 per lakh population annually. GATA3 is a recently used immunohistochemical marker which is highly sensitive for UC. Alterations in the p53 pathway play an important role in tumour progression and the assessment of prognosis. Aim: To study the expression of GATA3 and p53 in UC and their association with clinicopathological parameters. Materials and Methods: An ambispective cross-sectional study was conducted in the Department of Pathology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India, from September 2020 to August 2022. A total of 50 cases of histologically proven UC were subjected to immunohistochemistry with GATA3 and p53. The expression of GATA3 and p53 was evaluated in UC, and their association with clinicopathological parameters like age, gender, personal habits, tumour site, symptoms and signs, histological grade, and invasion into lamina propria and muscle was studied. The Chi-square test was used to determine the relationship between all parameters, with a p-value &lt;0.05 considered statistically significant. Results were analysed by standard software (Stata version 23.1). Results: GATA3 expression was observed in 94% (47/50) of cases of UC. GATA3 expression was associated with histological grade and muscle invasion, with 66.7% (4/6) expression in high-grade muscle-invasive UC, compared to 91.30% (21/23) in non muscle invasive UC, and 100% (21/21) in low-grade UC. Additionally, 66.7% (14/21) of low-grade UC showed p53 expression, whereas 80% (24/30) of high-grade UC demonstrated p53 expression. Conclusion: GATA3 is a sensitive and specific marker for UC. Its expression is highly variable among different histological types of UC and decreases with increasing grade of tumour in the study. p53 expression was associated with the histological grade of the tumour and was statistically significant in this study. GATA3 can be utilised to predict the probable grade of the tumour and its behaviour by correlating it with p53.

Significance of TERT promoter mutation in differential diagnosis of non-invasive inverted urothelial lesions of bladder

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.

Diagnostic Immunocytostaining with Peroxisome Proliferator-Activated Receptor-Gamma in Urine Cytology Samples

Introduction: Urine cytology is a common method for detection of urothelial carcinoma (UC), however, is not high sensitivity. Improvement of the accuracy of cytodiagnosis using immunocytostaining as an auxiliary method is needed. This study aimed to determine the cytodiagnostic usefulness of peroxisome proliferator-activated receptor-gamma (PPAR-γ) immunocytostaining in urine cytology for the detection of UCs, particularly low-grade urothelial carcinomas (LGUC). Methods: PPAR-γ immunocytostaining was performed for 37 UC cases and 26 benign cases. Among the UC cases, 22 cases were of the papillary proliferation type, not including the mixed type comprising both papillary and flat growth. Fifteen LGUC cases of all papillary proliferation types were included. For comparison, the same samples were also immunocytostained for p53 and Ki-67. Results: Of the UC cases, 25 of 37 were positive for PPAR-γ, while 24 of the 26 benign cases were PPAR-γ-negative. Regardless of histological grading, 13 of the 22 UC cases with papillary proliferation were PPAR-γ-positive. In particular, PPAR-γ immunocytostaining showed higher sensitivity for LGUC cases than that of the other biomarkers. Regarding LGUC specifically, 4 of 10 cases not identified by primary cytology were detected by PPAR-γ immunocytostaining. Conclusion: PPAR-γ immunocytostaining enhances the accuracy of urine cytodiagnosis. Furthermore, PPAR-γ is a more useful immunobiomarker in urine cytology than p53 and Ki-67, the commonly used immunobiomarkers for malignant cell detection.

Clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in Chinese population with mismatch repair deficient urothelial carcinoma: a real-world study.

Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.

The Relationship Between PD-1(rs2227981) and PD-L1(rs2890658) Polymorphisms and Urothelial Cell Carcinoma.

Background Urothelial cell carcinoma, which is believed to develop from the urothelium (transitional epithelium), is the most common aggressive tumor and accounts for the ten most prevalent cancers in the world. The risk factors for urothelial cell carcinoma are aging, smoking, gender, and genetic alternations. Programmed cell death1 (PD-1) has been widely described as a negative regulator of T-cells by sending inhibitory signals to the T-cell. Through PD-1 binding with PD-L1 (ligand for PD-1), an inhibitory signal is propagated to the T cell. The polymorphisms of PD-1 and PD-L1 lead to an efficient T-cell response and affect an anti-tumor reaction. The polymorphisms of PD-1 and PD-L1 could also affect the carcinogenesis of human cancer, including urothelial cell carcinoma. Therefore, in this study, we evaluated the relation between PD-1(rs2227981) and PD-L1(rs2890658) polymorphisms and the carcinogenesis of urothelial cell carcinoma. Materials and methods This study was conducted using 211 healthy controls and 256 cases of urothelial cell carcinoma among the Japanese population. The DNA samples were extracted from the peripheral white blood cells of each subject. The genotype was detected by using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results C/T (Adjusted OR 1.55, 95% CI:1.02-2.35) and C/T+T/T (OR 1.46, 95% CI:1.01-2.12) genotypes of PD-1 rs2227981 were significant and risk factors for urothelial cancer.Male with A/A genotype in PD-L1 and CT genotype in PD-1 has a significant higher risk factor compared with other genotypes (Adjusted OR 1.83, 95% CI:1.05-3.21). Conclusions and discussion We found that C/T(PD-1) and "A/A (PD-L1) and C/T(PD-1)" were predominant in urothelial cell carcinoma cases. This indicates that C/T(PD-1) and "A/A (PD-L1) and C/T(PD-1)" genotypes could increase susceptibility to urothelial cell carcinoma. However, since our findings indicated that the effects of PD-1 and PD-L1 polymorphisms included discrepancies, additional research will be needed to evaluate the relationship between human cancer and PD-1 and PD-L1 polymorphisms. This is the first study that seeks to find the relation between PD-1(rs2227981) and PD-L1(rs2890658) polymorphisms concerning urothelial cell carcinoma among the Japanese population.

Immunohistochemical expression of TROP‑2 (TACSTD2) on the urothelial carcinoma of the urinary bladder and other types of cancer.

In metastatic or locally advanced urothelial carcinoma (UC), therapeutic options have been limited to chemotherapy and immune checkpoint inhibitors. Novel targets and drugs such as antibody drug conjugates have been developed, and enfortumab vedotin targeting nectin-4 and sacituzumab govitecan (SG) targeting trophoblast cell surface antigen 2 (TROP-2), the protein product of the TACSTD2 gene, have been approved. The expression of TROP-2 was investigated within UC and other types of carcinomas, and within the tissue of different healthy organs to understand treatment responses and toxicities. The expression of TROP-2 in the tissues of 42 patients with UC, 13 patients with other types of cancer and in the normal tissues of 11 patients was retrospectively analyzed. Immunohistochemical staining of the TROP-2 protein was performed on a BenchMark ULTRA IHC/ISH System (Roche Tissue Diagnostics; Roche Diagnostics, Ltd.) according to accredited staining protocols in a routine immunohistochemistry accredited and certified facility of the laboratory of immunohistochemistry at the Institute of Pathology (Gerhard-Domagk Institute)- University Hospital Muenster (UKM)-Muenster-Germany]. Different expression levels of TROP-2 were observed, and the highest expression rate of TROP-2 was observed in UC, independent of the tumor stage. However, normal urothelial cells had similar expression levels. Except for ductal carcinoma in situ, the expression of TROP-2 was reduced in other types of cancer and in the healthy tissues from other organs, including pancreas, gall bladder, colon and prostate. Given the treatment response based on the expression level of TROP-2, SG would be effective in almost all cases of UC. However, it would also have an effect on the normal urothelium.

Clinicopathological characteristics, surgical treatments, and oncological outcomes of localized primary unifocal urothelial carcinoma involving the ureterovesical junction.

To investigate clinicopathological characteristics, surgical treatments, and oncological outcomes of patients with localized primary unifocal urothelial carcinoma involving the ureterovesical junction (UC-UVJ). Localized primary unifocal UC-UVJ cases in patients admitted to our hospital from March 2013 to August 2021 were reviewed. Clinicopathological parameters, perioperative data, and oncological outcomes were compared between patients grouped by tumor location and surgical treatment. A total of 130 patients with localized primary unifocal UC-UVJ were enrolled in this study. These included 72 cases of bladder cancer (BC) involving the ureteral orifice, and 58 cases of upper urinary tract urothelial carcinoma (UTUC) involving the intramural ureter. The proportion of male patients, hydronephrosis, flank pain/abdominal pain, and tumor size differed significantly between the BC and UTUC groups (all P < 0.05). During the median follow-up period of 32.9months, 49 cases (37.7%) recurred and 29 (22.3%) died from urothelial carcinoma (UC), though no statistical difference in recurrence (P = 0.436) or cancer-specific mortality (P = 0.653) was observed between the BC and UTUC groups. Cox proportional hazards regression analysis identified age, tumor grade, and lymphovascular invasion (LVI) as independent predictors of cancer-specific survival (CSS), and sex, T stage, tumor grade, and LVI as independent predictors of recurrence-free survival (RFS). Owing to positional properties, patients with localized primary unifocal UC-UVJ exhibited significant heterogeneity, leading to varied treatment strategies. No statistically significant differences in CSS or RFS were observed between the BC and UTUC groups. Furthermore, age, sex, T stage, tumor grade, and LVI should be carefully considered in clinical practice because of their associations with CSS and RFS.

Overview, Diagnosis, and Perioperative Systemic Therapy of Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinoma comprises 5-10% of all urothelial carcinoma cases. This disease tends to have a more aggressive course than its lower urinary tract counterpart, with 60% of patients presenting with invasive disease and 30% of patients presenting with metastatic disease at diagnosis. The diagnostic workup of UTUC involves imaging with CT urogram, urine cytology, and direct visualization and biopsy of suspected lesions via ureteroscopy. Standard treatment of high-grade UTUC involves radical nephroureterectomy (RNU) and excision of the ipsilateral bladder cuff. Both the NCCN and EAU Guidelines include neoadjuvant chemotherapy as a treatment option for select patients with UTUC; however, there are no strict guidelines. Much of the rationale for neoadjuvant chemotherapy is based on extrapolation from data from muscle-invasive bladder cancer, which has demonstrated a 5-year OS benefit of 5-8%. Retrospective studies evaluating the use of NACT in urothelial carcinoma have yielded pathologic objective response rates of 48% in UTUC cohorts. The randomized Phase III POUT study noted a DFS advantage with adjuvant platinum-based chemotherapy, compared with surveillance in UTUC, of 70% vs. 51% at 2 years. Though not the standard of care, multiple studies have explored the use of perioperative immunotherapy or chemoimmunotherapy in the management of invasive urothelial carcinoma. The PURE-02 study explored the use of neoadjuvant pembrolizumab in patients with high-risk UTUC. A small study of 10 patients, it showed no significant signals of activity with neoadjuvant pembrolizumab. Another Phase II study of neoadjuvant ipilimumab and nivolumab in cisplatin-ineligible UTUC yielded more promising findings, with 3/9 patients attaining a pathologic CR and the remaining six pathologically downstaged. The ABACUS trial found a 31% pathologic complete response rate amongst cisplatin-ineligible MIBC patients treated with neoadjuvant atezolizumab. The use of adjuvant immunotherapy has been explored over three phase III trials. The CheckMate-274 trial found a DFS benefit with the addition of one year of adjuvant nivolumab in patients with high-risk urothelial carcinoma. The IMvigor-010 study of adjuvant atezolizumab was a negative study. The AMBASSADOR trial of adjuvant pembrolizumab is pending results. With the FDA approval of erdafitinib in metastatic urothelial carcinoma, similar targets have been explored for use in perioperative use in invasive urothelial carcinoma, as with adjuvant infigratinib in the PROOF-302 trial. As the treatment paradigm for urothelial carcinoma evolves, further prospective studies are needed to expand the perioperative treatment landscape of UTUC.

High grade urothelial carcinoma in kidney transplant patients with a history of BK viremia - Just a coincidence?

Kidney transplant recipients (KTR) have a three-to-four-fold increased risk of developing urothelial carcinoma (UC) compared to the general population. BK polyoma virus (BKV) infection is known to affect approximately 15% of KTR. In vitro models support a potential pathogenic role for BKV in the development of UC. We describe a series of UC in kidney transplant recipients. Electronic patient records were searched to identify KTR with UC who had undergone kidney only or simultaneous kidney and pancreas transplantation in a single UK center between 2009 and 2015. Where available, stored pathological samples were retrieved, re-examined and stained for SV40 as a marker of BKV using standard staining protocols for kidney biopsy samples. Fourteen KTR had developed UC post-transplant. Of these, 10 KTR had a history of BKV infection post-transplant. Six of these 10 KTR developed a rare micropapillary tumor subtype of UC which is typically only found in <1% of UC cases. All six micropapillary tumor samples stained positive for SV40, including samples from metastases. Three tumor samples were available from the four KTR with no history of BKV infection and were not micropapillary subtype and were negative for SV40. Three micropapillary tumors from immunocompetent patients were examined as controls and were negative for SV40. These findings would support a pathogenic role for BK virus in the development of rare micropapillary subtype urothelial tumors in the kidney transplant population.

Clinicopathologic features and prognostic significance of mixed (Low and high-grade) papillary urothelial carcinoma comparison with low and high-grade papillary urothelial carcinoma.

The World Health Organization/International Society of Urological Pathology (2022 WHO/ISUP) classification categorizes noninvasive carcinomas based on the highest grade observed in a pathology sample. According to this classification, a lesion is classified as mixed-grade (MG) if the highest-grade component comprises less than 5% high-grade (HG) carcinoma [14]. This study included 160 cases of low-grade papillary urothelial carcinoma (LGUC) and 160 cases of HG papillary urothelial carcinoma (HGUC), selected randomly. In addition, 160 consecutive and unselected cases of MG papillary urothelial carcinoma (MGUC) were obtained from all bladder transurethral resection specimens diagnosed with papillary urothelial carcinoma between January 2007 and January 2021. The results of the multivariate analysis showed that histologic grade, invasion of the lamina propria, and the presence of carcinoma in situ at presentation were independent prognostic parameters regarding recurrence-free survival (p = 0.002; hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.059-1.956, p = 0.02; and HR = 1.76, 95% CI = 1.159-2.684, p = 0.008, respectively). Histologic grade was the only independent prognostic parameter of disease-specific survival (DSS) (p < 0.001). Comparisons between non-muscle invasive (NMI) MGUC and NMI LGUC, as well as between NMI MGUC and NMI HGUC, revealed statistically significant differences in terms of DSS (HR = 0.07, 95% CI = 0.024-0.252,p< 0.001 and HR = 1.59, 95% CI = 1.023-2.460, p = 0.039, respectively). Our study findings demonstrate statistically significant differences regarding DSS between NMI MGUC and NMI HGUC, as well as between NMI MGUC and NMI LGUC. Therefore, we suggested that considering the presence of less than 5% MGUC as a separate category may be appropriate. However, it is important to validate our results in larger cohorts with longer follow-up periods to establish the clinical significance of MGUC and provide guidance for patient management.

A clinical and pathologic study of muscle invasive urothelial carcinoma. Does the grade really matter?

PurposeThe purpose of our study is to correlate grade of Muscle invasive urothelial carcinoma with prognosis of patients in terms of disease recurrence, metastasis and death. Materals and methodsWe retrieved 48 cases of invasive urothelial carcinomas which on initial presentation had invaded muscularis propria (pT2) or beyond muscularis propria (pT3 or pT4), diagnosed and treated in Shaukat Khanum Memorial hospital Lahore and whose 8–20 years follow up data was available in hospital archives received either as Transurethral resection or cystectomy specimens from 2002 to 2015. Cases diagnosed as primary adenocarcinomas, Neuroendocrine carcinomas or other bladder malignancy other than urothelial carcinoma were excluded. ResultsAll 48 pT2 and higher stage patients were high grade. 34/48(70.8%) patients had disease recurrence, 11/48(22.9%) had no recurrence of disease and 3 patients lost to follow up. 43/48(89.5%) patients developed disease metastasis while 5/48(10.4%) did not develop metastatic disease. 39/48(81.2%) died of disease, 3 patients lost to follow up while 6/48(12.5%) patients survived. 5 out of 6 patients who survived had underwent cystectomy while 6 more underwent cystectomy but still died of disease. ConclusionMuscle invasion is itself an independent prognostic factor in predicting prognosis of patients and grade of such tumors is not much helpful as either majority of tumors are high grade or even if they are low grade, the prognosis is not good.

Clinicopathologic Analysis of Micropapillary Urothelial Carcinoma of the Upper Urinary Tract: Implications for HER2-Targeted Therapy.

Introduction/Background To determine the clinical significance of micropapillary urothelial carcinoma (MPUC) of the upper urinary tract (UTUC) and a potential therapeutic strategy. Patients and Methods A retrospective cohort study was conducted to examine the incidence of micropapillary UTUC from 2010 to 2018 and its clinicopathological characteristics. Clinical outcomes and cancer-specific survival (CSS) were compared between MPUC and conventional UTUC matched by stage within a 6-month variation of receiving surgery. Results A total of 24 MPUC cases were identified out of 901 cases (2.7%) of urothelial carcinoma (UC) of the renal pelvis and ureter. MPUC was significantly smaller (<3 cm) and associated with nodal metastasis compared with conventional UTUC (P=.017 & 0.021, respectively); however, no significant difference was observed for lymphovascular invasion, distant metastasis, or CSS (P > 0.50, respectively) compared with match controls. Six MPUC patients (25%) developed metastasis to the liver, lymph nodes, and lung during follow-up. Patients with HER2-positive MPUC (3 of 4) had a significantly higher risk of metastasis compared with HER2-negative MPUC (3 of 20; P=0.035). Conclusions MPUC is an aggressive variant of UTUC and usually presents as a small locally advanced disease. HER2 immunohistochemistry may identify the subset of patients with micropapillary UTUC that are candidates for targeted therapy.

Is a Single Nephrographic Phase Computed Tomography Sufficient for Detecting Urothelial Carcinoma in Patients with Visible Haematuria? A Prospective Paired Noninferiority Comparison

BackgroundThere is uncertainty about the utility of multiphase computed tomography (CT) compared with single-phase CT in the routine examination of patients with visible haematuria (VH). ObjectiveTo compare the accuracies of single nephrographic phase (NP) CT and four-phase CT in detecting urothelial carcinoma (UC). Design, setting, and participantsThis was a single-centre, prospective, paired, noninferiority study of patients with painless VH referred for CT before cystoscopy between September 2019 and June 2021. Patients were followed up for 1 yr to ascertain UC diagnosis. InterventionAll patients underwent four-phase CT (control), from which single NP CT (experimental) was extracted. Both were independently assessed for UC. Outcome measurements and statistical analysisThe primary outcome was the difference in accuracy between the control and experimental CT using a 7.5% noninferiority limit. Histologically verified UC defined a positive reference standard. Secondary outcomes included differences in sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and area under the curve (AUC). All results are reported per patient. Results and limitationsOf the 308 patients included, UC was diagnosed in 45 (14.6%). The difference in accuracy between the control and experimental CT was 1.9% (95% confidence interval −2.8 to 6.7), demonstrating noninferiority. Sensitivity was 93.3% versus 91.1%, specificity was 83.7% versus 81.8%, NPV was 98.7% versus 98.2%, PPV was 49.4% versus 46.1%, and AUC was 0.96 versus 0.94 for the control versus experimental CT. Limitations included a low number of UC cases and no definite criteria for selecting a noninferiority limit. ConclusionsThe accuracy of NP CT is not inferior to that of four-phase CT for detecting UC. Patient summaryThis study shows that a computed tomography (CT) examination with only one contrast phase is no worse than a more complex CT examination for detecting cancer in the urinary tract among patients presenting with visible blood in the urine.

CD105 and CD34 as Markers of Angiogenesis of Urothelial Carcinoma: A Cross Sectional Study

Background Urothelial carcinoma (UC) of the bladder is a major cause of morbidity and mortality throughout the world. The present study was carried out to see the expression of CD105 and CD34 as marker of angiogenesis in UC and study their relationship with grades and muscle invasion. Methods 50 cases of histopathologically diagnosed UC were included. CD105 and CD34 IHC staining was performed. Microvessel density (MVD) evaluation by CD105 and CD34 was compared. The number of microvessels were counted in high power in three hot spots. The highest value obtained amongst three fields were reported as MVD. Statistical analysis was done by (SPSS 28.00 version for windows) using independent t-test. Results There were 45 high grade cases UC 5 low grade cases of UC. Invasive papillary UC was seen in 25 cases (50%) followed by invasive UC seen in 13 cases (26%). Both Lamina propria (LP) invasion and muscularis propria invasion were noted in 16 cases of high-grade urothelial carcinoma. Only LP invasion was seen in 3 cases of low grade and 25 cases of high-grade UC respectively. Evaluation of MVD CD105 and MVD CD34 did not show any significant association of MVD with grade with a p value of 0.214 &amp; 0.429 respectively. Aso there was no significant association of MVD CD105 (p=0.580) &amp; CD34 (p=0.747) with muscularis propria invasion. Overall mean CD105 and CD34 were similar with no statistical difference between the two markers. Conclusion Both CD105 and CD34 can be used as marker to assess angiogenesis. However, there is no significant association of MVD with grade or muscle invasion in UC.

EphrinB2: Expression of a novel potential target in renal cell carcinoma.

Renal cell carcinoma (RCC) is primarily managed by surgery with the use of systemic targeted therapy in a metastatic setting. Newer targeted therapeutic options are evolving; Eph-ephrin is a potential new pathway. The therapeutic potential of targeting the EphB4-EphrinB2 pathway has been demonstrated in many solid tumors; however, its expression in RCC has only been evaluated in a few studies with limited cases. We herein determine the immunohistochemical expression of EphrinB2 in RCC. A tissue microarray comprising 110 cases of different histological subtypes of RCC and 10 normal kidney tissues were stained with monoclonal anti-EphrinB2 antibody (Abcam, AB201512). The tumor and endothelial cells expressing the EphrinB2 were examined and its expression was correlated with sex, histological subtypes, and tumor nodes metastasis (TNM) stage. Twenty cases of urothelial carcinoma and two unsatisfactory conventional clear cell RCC cases were excluded, and EphrinB2 expression was interpreted in the remaining 88 tumors. EphrinB2 was expressed in 42 out of 88 tumors (47.7%) and was negative in the normal renal parenchyma. There was a statistically significant difference in the expression of EphrinB2 in males (55%) and females (32%). However, no such difference of expression was noted for the histological subtypes and the stages. Half (51%) of Stage 1 (n = 30) and Stage 2 (n = 11) tumors showed EphrinB2 positivity. EphrinB2 is expressed in approximately half of RCC cases. EphrinB2 expression in the early stage cancer might indicate its induction as an early event.

The preliminary efficacy of "quadri-combination" therapy on the treatment of bladder cancer

To investigate the safety and efficacy of "quadri-combination" therapy including maximal transurethral resection of bladder tumor (mTURBT), combined with systemic chemotherapy and immunotherapy, concurrent radiotherapy, and immune maintenance therapy. The clinical data of 8 patients with bladder cancer who could not tolerate or refused radical cystectomy at the Department of Urology, Peking University Cancer Hospital from November 2019 to October 2021 were retrospectively analyzed. There were 5 males and 3 females with a mean age of 69 years. The Eastern Cooperative Oncology Group(ECOG) score was 0 in 6 cases and 1 in 2 cases. There were 5 cases of high-grade urothelial carcinoma (1 case of T3b; 2 cases were T2; 2 cases of T1 stage, with multiple tumors and repeated recurrence), 1 case of high-grade urothelial carcinoma with carcinoma in situ (T1/Tis stage), 1 case of high-grade urothelial carcinoma with squamous differentiation (T3b stage), and 1 case of high-grade urothelial carcinoma with glandular differentiation (T2). All patients underwent "quadri-combination" therapy.The patient's tolerance, success rate of bladder preservation and prognosis were evaluated.The median follow-up time was 22.5 (12-35) months. One patient with high-grade muscle-invasive bladder cancer (T2) received mTURBT, albumin-bound paclitaxel and durvalumab combined therapy for 3 cycles, concurrent radiotherapy, and immune maintenance therapy for 18 months, and the tumor recurrence was found. The pathology was high-grade urothelial carcinoma. Salvage radical cystectomy combined with pelvic lymph node dissection is recommended. The remaining 7 patients were regularly reexamined, and no recurrence or metastasis was found.The 2-year progression-free survival rate was 80%, and the success rate of bladder preservation was 87.5%(7/8). Treatment-related adverse reactions were resolved by symptomatic treatment, and patients' compliance and tolerance were acceptable.The "quadri-combination" bladder-preserving therapy is feasible and well tolerated, but further studies are needed.

Expression of androgen receptor in bladder cancer: A tertiary care center study

IntroductionThe significance of androgen receptor (AR) expression in bladder cancer is the focus of current research. This study aimed to assess the significance of AR expression in bladder urothelial carcinoma. MethodsA total of 206 cases of urothelial carcinoma of the urinary bladder were reviewed and immunohistochemical staining for AR was performed. The histological score was calculated as the product of the staining intensity and percentage of cells with positive nuclear staining. The staining results were correlated with demographic parameters, tumor grade, and detrusor muscle invasion status. ResultsSeventy-eight percent (n = 161) of cases tested positive for AR expression. AR was significantly overexpressed in non-muscle-invasive tumors (p = 0.042). Moreover, A higher AR expression was associated with increased disease-free survival (p = 0.019). However, AR expression was not significantly associated with cancer-specific survival, patient sex, or tumor grade (0.359, 0.747, and 0.867, respectively). AR expression is inversely related to muscle invasion and recurrence in bladder cancer. ConclusionThe results of this study support those of several reports worldwide. Further molecular studies are required to elucidate the role of androgens in bladder cancer pathogenesis and therapy.