Urothelial Cancer Cases Research Articles

Challenging Cases in Urothelial Cancer: Case 33

Challenging Cases in Urothelial Cancer: Case 33

Abstract 1073: AI-assisted high-dimensional cytological single cell analysis distinguishes normal and malignant urine samples using cell morphology images with high accuracy at the single cell level

Abstract Background: Urothelial cancer (UCC) is the 4th most common malignancy in men. The current clinical problem in UCC management is the high interobserver variability of tissue UCC grading and the low sensitivity of urine cytology for early detection of recurrences and progression. We hypothesize that assessing urine samples and UCC tissues with detailed quantitative image analysis based on artificial intelligence has strong potential in both urine-based early detection of tumor recurrence and progression as well as tissue-based pathological grading. Methods: Here, we utilized the Deepcell® Human Foundation Model (HFM), a self-supervised deep learning model, to assess a cohort of urine samples from 54 normal healthy cases, 19 atypical cases, and 4 UCC cases. High resolution images of label-free single cells were captured and analyzed using the HFM to identify distinct morphological characteristics of cells from different urine origins. The urine samples were loaded onto a single-use microfluidic cartridge as part of the Deepcell® REM-I platform and brightfield images of single cells were captured in real-time. For data analysis, images of all cells run through the REM-I instrument are automatically sent to the Deepcell® Axon Suite, which provides an analysis platform to visualize cell images from specific runs, generate UMAPs of the embedding space, and run additional deep neural network models on samples in silico. Results: High-dimensional analysis of 115 deep learning and morphometric features reveals 12 morphotypes among the pooled urine samples, as represented by morphology UMAP plots. Morphology analysis reveals distinct morphotypes in normal compared to pathological urine samples. Confusion matrix showed deep learning model performance in classifying atypical versus UCC with 89.1% (Atypical (n = 8642), UCC (n = 12637)). This indicates high model performance accuracy for AI prediction of atypical versus UCC samples at the single cell level. Conclusions: The Deepcell® REM-I platform performs well with urine samples and identified numerous cell clusters among normal and pathological urines. AI-assisted high-dimensional morphology analysis distinguishes atypical urine samples from UCC cases with 89.1% accuracy at the single cell level. Future applications of this study include early detection or monitoring of UCC cases using non-invasive patient samples such as urine. Citation Format: Thierry P. van den Bosch, Geert J.L.H. van Leenders, Siamala Sinnadurai, Zhouyang Lian, Ryan Carelli, Matthew Nakaki, Vivian Lu, Manisha Ray, Janifer Cruz, Kelly R. Miller, Mahyar Salek, Maddison Masaeli, Peter J. van der Spek. AI-assisted high-dimensional cytological single cell analysis distinguishes normal and malignant urine samples using cell morphology images with high accuracy at the single cell level [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1073.

Survival and Enrichment Analysis of Epithelial-Mesenchymal Transition Genes in Bladder Urothelial Carcinoma.

The escalating prevalence of bladder cancer, particularly urothelial carcinoma, necessitates innovative approaches for prognosis and therapy. This study delves into the significance of genes related to epithelial-mesenchymal transition (EMT), a process inherently linked to carcinogenesis and comparatively better studied in other cancers. We examined 1184 EMT-related gene expression levels in bladder urothelial cancer cases through the TCGA dataset. Genes shown to be differentially expressed in relation to survival underwent further network and enrichment analysis to uncover how they might shape disease outcomes. Our in silico analysis revealed a subset of 32 genes, including those significantly represented in biological pathways such as VEGF signaling and bacterium response. In addition, these genes interact with genes involved in the JAK-STAT signaling pathway. Additionally, some of those 32 genes have been linked to immunomodulators such as chemokines CCL15 and CCL18, as well as to various immune cell infiltrates. Our findings highlight the prognostic utility of various EMT-related genes and identify possible modulators of their effect on survival, allowing for further targeted wet lab research and possible therapeutic intervention.

Reproductive factors in the risk of bladder cancer and upper urinary tract cancer: The Japan Public Health Center-based Prospective Study.

Reproductive factors are hypothesized to play a role in the incidence of bladder cancer (BC) and upper urinary tract cancer (together, urothelial cancer (UC)). However, evidence regarding these associations is limited, particularly in Asian populations. We analyzed data from 55,882 females aged 40-69 years, and performed Cox proportional hazards regression analyses with three types of adjustment, namely age; reproductive factor of interest and covariates in addition to age (conventional model); and other reproductive factors in addition to the multivariable adjusted model (reproductive model). During an average of 20.2 years of follow-up, 194 UC cases (145 BC cases and 49 UUTC cases) were identified. Early age at natural menopause (<44 years, compared to 49-51 years) increased BC risk in the reproductive model (HR=2.09 (95% CI=1.04-4.20)). An association between UC/BC and age at menopause, including both natural and surgical/induced, was significant in the reproductive model [HR=1.74 (95% CI=1.09-2.77), and HR=1.94 (95% CI=1.15-3.28), respectively]. Early age at natural menopause was suggested to increase UC risk in the reproductive model (HR=1.78 (95% CI=0.93-3.42)). Our findings suggest a significant association between age at menopause and incidence of UC/BC among Asian populations. This study aids understanding the role of reproductive factors in UC/BC incidence. In Japanese populations, age at menopause is suggested to be associated with UC/BC incidence, especially regarding early natural menopause.

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma.

The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Survival outcomes of micropapillary versus classic variant, loco-regional bladder cancer: A 2004-2019 National Cancer Database analysis.

4592 Background: Micropapillary (MP) is a rare histologic variant of urothelial cancer (UC) with luminal-type characteristics and p53-like gene expression, leading to chemotherapy resistance and poor prognosis. However, contemporary outcomes of MP variant T2-T4, N0-N1 loco-regional bladder UC after definitive therapy are underreported, which this work sought to determine. Methods: A retrospective review was performed of all eligible cases of MP and classic UC (CUC) available during 2004-2019 from National Cancer Database. Socio-demographic, pathological, and clinical attributes were analyzed via descriptive and comparative statistics. Propensity-score matching was performed to adjust for baseline differences between MP and CUC. Overall survival, being the primary outcome, was compared using multivariable Cox proportional-hazards modeling and visualized through Kaplan-Meier curves. Results: 30072 cases of CUC and 397 of MP were identified. After propensity-score matching, 395 patients remained in both groups, with matched cohorts having no baseline differences in age, sex, race, Charlson-Deyo comorbidity index (CCI), insurance status, income, distance to hospital, hospital location, rural versus urban residence, tumor pathological grade, proportion receiving radiotherapy, and proportion getting regional lymph node surgery. In both matched cohorts there were 313 males (79%) and 82 females (21%). Both cohorts had 334 (85%) T2 cases, 41 (10%) T3 cases, and 20 (5%) T4 cases. Both cohorts had 375 (95%) N0 cases and 20 (5%) N1 cases. MP variant was associated with inferior survival compared to CUC (HR 1.26, 95%CI 1.03-1.54, P=0.024). Older age (≥65 years) and higher CCI were also associated with inferior survival. Irrespective of histology, patients undergoing surgery (S) plus chemotherapy (C) had better survival compared to S alone (HR 0.77, 95%CI 0.62-0.94, P=0.012). Regional lymph node surgery resulted in improved survival (HR 0.59, 95%CI 0.42-0.83, P=0.002). Sex, race, insurance, income, and hospital type did not impact survival. Median and two-year OS are summarized. Conclusions: Survival outcomes of MP are poorer than CUC of bladder. Surgery combined with perioperative chemotherapy was associated with better survival compared to surgery alone in patients with MP and CUC. Studies evaluating novel immunotherapies and antibody drug conjugates in perioperative setting are needed to improve outcomes. [Table: see text]

Pevonedistat Inhibits SOX2 Expression and Sphere Formation but Also Drives the Induction of Terminal Differentiation Markers and Apoptosis within Arsenite-Transformed Urothelial Cells.

Urothelial cancer (UC) is a common malignancy and its development is associated with arsenic exposure. Around 25% of diagnosed UC cases are muscle invasive (MIUC) and are frequently associated with squamous differentiation. These patients commonly develop cisplatin (CIS) resistance and have poor prognosis. SOX2 expression is correlated to reduced overall and disease-free survival in UC. SOX2 drives malignant stemness and proliferation in UC cells and is associated with development of CIS resistance. Using quantitative proteomics, we identified that SOX2 was overexpressed in three arsenite (As3+)-transformed UROtsa cell lines. We hypothesized that inhibition of SOX2 would reduce stemness and increase sensitivity to CIS in the As3+-transformed cells. Pevonedistat (PVD) is a neddylation inhibitor and is a potent inhibitor of SOX2. We treated non-transformed parent and As3+-transformed cells with PVD, CIS, or in combination and monitored cell growth, sphere forming abilities, apoptosis, and gene/protein expression. PVD treatment alone caused morphological changes, reduced cell growth, attenuated sphere formation, induced apoptosis, and elevated the expression of terminal differentiation markers. However, the combined treatment of PVD with CIS significantly elevated the expression of terminal differentiation markers and eventually led to more cell death than either solo treatment. Aside from a reduced proliferation rate, these effects were not seen in the parent. Further research is needed to explore the potential use of PVD with CIS as a differentiation therapy or alternative treatment for MIUC tumors that may have become resistant to CIS.

Clinical and diagnostic observation of transitional cell carcinoma recurrence in the ureteral stump: a case report

Urothelial cancer of the upper urinary tract is quite rare and accounts for 5–10% of all cases of urothelial cancer. Radiation research methods, primarily computer and magnetic resonance imaging, are leading in monitoring and detecting recurrence after surgery on the organs of the urinary system. A rare clinical case of recurrence of transitional cell carcinoma of the upper urinary tract in the ureteral stump is presented. The article, with an emphasis on radiodiagnosis, outlines a step-by-step follow-up of a patient with primary cancer of the upper third of the ureter (рT2N0M0), who was hospitalized in the city clinical hospital for pain in the right lumbar region. During dynamic contrast enhancement multiparametric MRI, a recurrence of the disease was established with a lesion of the non-removed stump of the right ureter. Semiotic MR signs of recurrence of transitional cell carcinoma of the upper urinary tract are described. The recurrent tumor of the ureteral stump was characterized by a moderate hyperintense T2WI MR signal and an isointense T1WI MR signal. Our data indicate lower ADC values in the tumor when measured by a large ROI (937 mm2, versus 796 mm2 ROI with a small size). The dynamic contrast enhancement performed in our study showed intensive accumulation of the contrast by the recurrent tumor.

Abstract 734: History of diabetes is differentially associated with urothelial cancer risk in understudied racial/ethnic groups in the Multiethnic Cohort Study (MEC)

Abstract Background: Type 2 diabetes (T2D) is an established risk factor for urothelial cancer (UC), however there is very little data characterizing this association in populations of non-European ancestry. Understanding the relationship between T2DM and UC across multiple populations is important since both risk and severity of each condition differ according to race and ethnicity. Methods: We estimated the association between T2D and UC among 185,587 MEC participants who were between 45 and 75 years old at enrollment (1993-1996) and from five major racial/ethnic groups (African Americans, Japanese Americans, Native Hawaiians, Latinos, and non-Hispanic whites). T2D status was assessed by self-report at cohort entry. UC cases were identified through linkages to statewide SEER cancer registries. We estimated the association between T2D and UC using Cox regression, adjusting for known confounders (smoking duration, smoking intensity, alcohol consumption, body mass index), stratifying on sex, age, and ethnicity. Using the full model, we assessed heterogeneity of associations by race/ethnicity. Results: Over a mean of 19 years of follow-up, 2,398 incident UC cases were identified. The prevalence of T2D was highest among African Americans (15.7%), followed by Latinos (15.6%), Native Hawaiians (14.8%), Japanese Americans (10.5%), and non-Hispanic whites (5.9%). The age-standardized UC incidence rates were highest among whites (60/100,000) followed by Japanese Americans (42/100,000), Native Hawaiians (40/100,000), African Americans (37/100,000), and Latinos (29/100,000). Incidence of UC was 1.11 (95% CI: 0.97, 1.26)-fold greater in those who reported a history of T2D, and this association differed between racial-ethnic groups (pheterogeneity=0.04). Estimates of the association between T2D and UC achieved statistical significance among African Americans (HR=1.49; 95% CI: 1.12, 1.98) and Native Hawaiians (HR=1.68; 95% CI: 1.08, 2.60), but not among non-Hispanic whites (HR=1.06; 95% CI: 0.78, 1.43), Latinos (HR=0.96; 95% CI: 0.71, 1.29), or Japanese Americans (HR=0.95; 95% CI: 0.75, 1.21). Conclusions: In this multiethnic analysis, estimates of the association between T2DM and UC were strongest among African American and Native Hawaiian participants. The apparently stronger associations in these groups may be due to greater severity and/or poorer control of T2DM. African Americans and Native Hawaiians may benefit from targeted interventions to better manage T2D in these populations to reduce risk of UC. Citation Format: David Bogumil, Victoria Cortessis, Lynne Wilkens, Veronica Wendy Setiawan, Christopher Haiman, Loic Le Marchand, Gertraud Maskarinec. History of diabetes is differentially associated with urothelial cancer risk in understudied racial/ethnic groups in the Multiethnic Cohort Study (MEC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 734.

MP54-07 A URINE-BASED MOLECULAR ASSAY REFINES THE RISK STRATIFICATION OF THE RECENT AMERICAN UROLOGICAL ASSOCIATION GUIDELINE ON HEMATURIA

You have accessJournal of UrologyCME1 May 2022MP54-07 A URINE-BASED MOLECULAR ASSAY REFINES THE RISK STRATIFICATION OF THE RECENT AMERICAN UROLOGICAL ASSOCIATION GUIDELINE ON HEMATURIA Joep de Jong, Olga Pijpers, Kim van Kessel, Joost Boormans, Wim van Criekinge, Ellen Zwarthoff, and Yair Lotan Joep de JongJoep de Jong More articles by this author , Olga PijpersOlga Pijpers More articles by this author , Kim van KesselKim van Kessel More articles by this author , Joost BoormansJoost Boormans More articles by this author , Wim van CriekingeWim van Criekinge More articles by this author , Ellen ZwarthoffEllen Zwarthoff More articles by this author , and Yair LotanYair Lotan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002633.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: According to the recent American Urological Association (AUA) Guideline on Hematuria, patients are stratified into low, intermediate and high-risk groups. These risk groups are based on clinical risk factors and do not incorporate urine-based tumor markers. Previously, we validated a urine-based molecular assay in a large prospective cohort of patients referred for gross- or microscopic hematuria. Here, we applied the updated AUA guidelines onto this prospective cohort, integrating both clinical and molecular parameters for refined urothelial cancer risk prediction. METHODS: We selected all patients with complete biomarker status from a previously published prospective Dutch hematuria cohort, including 838 patients of whom 112 were diagnosed with urothelial cancer. Patients were stratified into AUA risk category low, intermediate or high risk based on sex, age and type of hematuria. Biomarker status included mutation status of the FGFR3, TERT and HRAS genes and methylation status of the OTX1, ONECUT2 and TWIST1 genes, as assessed on urinary patient DNA. The primary end point was the diagnostic model performance for different hematuria risk groups as indicated by the AUC. Further analyses assessed the pre- and post-test cancer probability within hematuria subgroups using Fagan’s nomograms. RESULTS: Overall, 65 patients (7.8%) were classified as low risk, 106 (12.6%) patients intermediate risk, and 667 patients (79.6%) were classified as high risk. The urothelial cancer incidence differed significantly between gross (21%, 98/457) and microscopic (4%, 14/381) hematuria subgroups (P <0.001). Notably, all cancer cases were among the high risk AUA category with an incidence of 16.8% (112/667). Application of the diagnostic model revealed robust performance among all evaluated hematuria risk groups (AUC’s 0.929-0.971), showing consistent sensitivities of >90%. However, specificity of the assay was only 53% for gross hematuria patients, while microscopic hematuria risk groups had consistent specificities of >90%. Depending on the evaluated hematuria risk group, a negative urine assay was associated with a post-test cancer probability of 0.3-2% and a positive urine assay was associated with a post-test cancer probability of 31-42%. CONCLUSIONS: This study suggests efficiency for incorporating a urine-based molecular assay after AUA guideline stratification based on clinical risk factors for evaluation of hematuria patients. The AUA high risk stratification is accurate and detects all urothelial cancer cases. In AUA low/intermediate risk categories, patients with a negative assay may be able to safely avoid cystoscopy. Furthermore, AUA high risk patients with a positive assay should have expedite evaluation. Source of Funding: Supported by MDxHealth and powered by Health Holland, Top Sector Life Sciences & Health © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e928 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joep de Jong More articles by this author Olga Pijpers More articles by this author Kim van Kessel More articles by this author Joost Boormans More articles by this author Wim van Criekinge More articles by this author Ellen Zwarthoff More articles by this author Yair Lotan More articles by this author Expand All Advertisement PDF DownloadLoading ...

Overexpression of Her-2 in Biopsy-Proven Urothelial Carcinoma Patients From Pakistan.

Background Bladder cancer is a common urological cancer. Her-2 gene is a proto-oncogene which is present in 17q12 chromosomal region. Her-2 overexpression has been seen in breast, gastric and ovarian cancers. The purpose of this study was to evaluate the incidence of overexpression of Her-2 in patients with urothelial carcinoma diagnosed by histopathology in the Pakistani population.MethodsThis is a cross-sectional observational study conducted on the biopsy samples of patients diagnosed with urothelial carcinoma in Histopathology Department of Chughtai Institute of Pathology from 15 September 2018 to 15 March 2021. The immunohistochemical analysis was done on serial sections using immune-enzymatic soluble complex method. The antibody used was Her-2 polyclonal antibodies from DAKO (Agilent, Santa Clara, USA). Her-2 scoring was done according to the College of American Pathologists (CAP) guidelines for reporting Her-2 overexpression in breast cancer.ResultsA total of 140 cases of urothelial cancer were included in the study. About 83.57% (n=117) of cases were males, and 16.42% (n=23) were females. Positive Her-2 staining was observed in 38/140 (27.15%) cases. A significant association was seen between Her-2 staining and muscle invasion (p-value=0.0001).ConclusionOur study shows that Her-2 overexpression is seen in a number of patients with urothelial carcinoma, especially in patients with muscle invasion. These patients may benefit from targeted therapy against the Her-2 gene. Her-2 overexpression evaluation should be considered in such patients.

S3121 A Rare Case of Urothelial Cancer Metastasizing to the Stomach

S3121 A Rare Case of Urothelial Cancer Metastasizing to the Stomach

Challenging Cases in Urothelial Cancer: Case 19.

Challenging Cases in Urothelial Cancer: Case 19.

Higher than expected and significantly increasing incidence of upper tract urothelial carcinoma. A population based study

PurposeTo register all cases of urothelial cancer and renal cell carcinoma (RCC) in Norway during 1999–2018 to obtain the contemporary incidence of UTUC and UTUC incidence relative to other urothelial cancers and RCC. Further to analyse possible changes over time regarding UTUC incidence, UTUC patient characteristics, tumour characteristics and survival.Methods3502 cases registered with ICD code C65 and C66 during 1999–2018 at the Norwegian cancer registry were entered into a database. After a selection process 3096 cases were included in the study. The crude incidences of UTUC were calculated for each year adjusting for the corresponding population data. Age-standardized rates adjusting to the European standard population (2013) were calculated. Comparisons were made with other cases of urothelial cancer and RCC. For changes over time, the material was split into 5-year periods. Regression analysis was used to calculate yearly changes and for assessing statistical significance. Survival outcomes were calculated using the Kaplan–Meier method.ResultsThe overall age-standardized incidence rate was 3.88, increasing from 3.21 to 4.70 from first to last 5-year periods. The increase affected all ages except those < 60 years of age, and were observed regardless of gender or anatomical location. UTUC constituted 11.8% of all urothelial cancers, increasing from 9.9 to 12.8%. Mean patient age at diagnosis increased from 71.5 to 73.4 years. The 5-years Cancer-specific survival improved from 57.4 to 65.4%.ConclusionThe incidence of UTUC was higher than expected and increasing. Patient age at diagnosis was increasing.

Lynch Syndrome: Its Impact on Urothelial Carcinoma.

Lynch syndrome, known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal-dominant familial cancer syndrome with an increased risk for urothelial cancer (UC). Mismatch repair (MMR) deficiency, due to pathogenic variants in MLH1, MSH2, MSH6, and PMS2, and microsatellite instability, are known for development of Lynch syndrome (LS) associated carcinogenesis. UC is the third most common cancer type in LS-associated tumors. The diversity of germline variants in the affected MMR genes and their following subsequent function loss might be responsible for the variation in cancer risk, suggesting an increased risk of developing UC in MSH2 mutation carriers. In this review, we will focus on LS-associated UC of the upper urinary tract (UUT) and bladder, their germline profiles, and outcomes compared to sporadic UC, the impact of genetic testing, as well as urological follow-up strategies in LS. In addition, we present a case of metastatic LS-associated UC of the UUT and bladder, achieving complete response during checkpoint inhibition since more than 2 years.

Challenging Cases in Urothelial Cancer: Case 181

Challenging Cases in Urothelial Cancer: Case 181

Challenging Cases in Urothelial Cancer: Case 171

Challenging Cases in Urothelial Cancer: Case 171

In-Vitro Identification and In-Vivo Confirmation of DNA Methylation Biomarkers for Urothelial Cancer.

We identified DNA methylation targets specific for urothelial cancer (UC) by genome-wide methylation difference analysis of human urothelial (RT4, J82, 5637), prostate (LNCAP, DU-145, PC3) and renal (RCC-KP, CAKI-2, CAL-54) cancer cell lines with their respective primary epithelial cells. A large overlap of differentially methylated targets between all organs was observed and 40 Cytosine-phosphate-Guanine motifs (CpGs) were only specific for UC cells. Of those sites, two also showed high methylation differences (≥47%) in vivo when we further compared our data to those previously obtained in our array-based analyses of urine samples in 12 UC patients and 12 controls. Using mass spectrometry, we finally assessed seven CpG sites in this “bladder-specific” region of interest in urine samples of patients with urothelial (n = 293), prostate (n = 75) and renal (n = 23) cancer, and 143 controls. DNA methylation was significantly increased in UC compared to non-UC individuals. The differences were more pronounced for males rather than females. Male UC cases could be distinguished from non-UC individuals with >30% sensitivity at 95% specificity (Area under the curve (AUC) 0.85). In summary, methylation sites highly specific in UC cell lines were also specific in urine samples of UC patients showing that in-vitro data can be successfully used to identify biomarker candidates of in-vivo relevance.

Challenging Cases in Urothelial Cancer

Challenging Cases in Urothelial Cancer

Challenging Cases in Urothelial Cancer

Challenging Cases in Urothelial Cancer