Urothelial Carcinoma Of The Urinary Bladder Research Articles

Plasmacytoid urothelial carcinoma of the urinary bladder–A clinicopathological and molecular analysis of 52 cases

Plasmacytoid urothelial carcinoma (UC) is a rare histologic subtype of bladder cancer that is associated with an aggressive clinical behavior. We analyzed the clinicopathologic and molecular features of plasmacytoid UC in 52 patients from a single institute. The patients included 44 men and 8 women, with a mean age of 64 years (range, 41–91 years). All bladder cancers were high-grade UC, and plasmacytoid component accounted for a mean of 47% of bladder tumors (range, 5–100%). Distinct gene mutations were found in most plasmacytoid UCs (n = 49); the most common mutations were TP53 (n = 30), followed by TERT (n = 20), and CDH1 (n = 18). Copy number analysis was performed in 34 patients, and 13 of them showed copy number variations. Expression of HER2 was analyzed in 18 patients by immunohistochemistry, and 3 of them showed HER2 overexpression, which was confirmed by fluorescence in situ hybridization analysis. Thirty-two patients died of disease in a median of 15 months (range, 1–45 months). No individual gene mutations were significantly associated with clinical outcome, but mutations in the mammalian target of rapamycin (mTOR) pathway, including PICK3CA and PIK3R1 mutations, were associated with a significantly shorter survival duration (p < 0.05). Plasmacytoid UC is an aggressive histologic subtype that demonstrates frequent somatic gene mutations and CNVs, which may underlie its oncogenesis and progression. Gene mutations of the mTOR pathway are associated with poor outcome in a subset of patients with plasmacytoid UC.

POU2F3-expressing intraepithelial small-cell carcinoma with mixed small-cell carcinoma and conventional-type urothelial carcinoma of the urinary bladder.

Based on lineage-specific transcription factors, small-cell neuroendocrine carcinoma (SmCC) of the urinary bladder has recently been subtyped into three molecular subtypes: ASCL1, NEUROD1 and POU2F3. The latter is a master transcriptional regulator of tuft cells (TCs) which are rare solitary cells found in various mucosal epithelia such as the gastrointestinal tract, but which have not been reported in the bladder. The POU2F3 subtype shows low or absent neuroendocrine marker expression. A case of mixed SmCC and conventional-type urothelial carcinoma (CUC) of the urinary bladder with POU2F3-expressing intraepithelial small-cell carcinoma in keeping with a tuft cell phenotype, arising in association with intestinal metaplasia (IM) is described. The presence of POU2F3-expressing cells in normal urothelium, cystitis cystica glandularis and IM of the urinary bladder is demonstrated in separate cases of cystitis cystica glandularis with IM. Also, POU2F3 expression is identified in a subset of bladder SmCC.

Non-Surgical Bladder-Sparing Multimodal Management in Organ-Confined Urothelial Carcinoma of the Urinary Bladder: A Population-Based Analysis.

Trimodal therapy is considered the most validated bladder-sparing treatment in patients with organ-confined urothelial carcinoma of the urinary bladder (T2N0M0). However, scarce evidence exists regarding cancer-specific mortality (CSM) differences between trimodal therapy and other non-extirpative multimodal treatment options such as radiotherapy alone after transurethral resection (TURBT + RT) or chemotherapy alone after transurethral resection (TURBT + CT). Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified T2N0M0 patients treated with either trimodal therapy, TURBT + CT, or TURBT + RT. Temporal trends described trimodal therapy vs. TUBRT + CT vs. TURBT + RT use over time. Survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM according to each treatment modality. 3729 (40%) patients underwent TMT vs. 4030 (43%) TURBT + CT vs. 1599 (17%) TURBT + RT. Over time, trimodal therapy use (Estimating annual percent change, EAPC: +1.2%, p = 0.01) and TURBT + CT use increased (EAPC: +1.5%, p = 0.01). In MCR models, relative to trimodal therapy, TURBT + CT exhibited 1-14-fold higher CSM and TURBT + RT 1.68-fold higher CSM. In a subgroup analysis, TURBT + RT was associated with 1.42-fold higher CSM than TURBT + CT (p < 0.001). Strict trimodal therapy that includes both CT and RT after TURBT offers the best cancer control. When strict trimodal therapy cannot be delivered, cancer-specific survival outcomes appear to be superior with TURBT + chemotherapy compared to TURBT + RT.

Abstract 2509: Abundant glucocorticoid receptor (GR) expression in human tumors: A tissue microarray study on more more than 18,000 tumors

Abstract The glucocorticoid receptor (GR, or GCR) is a nuclear receptor protein for cortisol and other glucocorticoids and regulates the transcription of thousands of genes involved in metabolism, development, stress, and inflammatory response. In cancer, both an oncogenic and a tumor suppressive function of GR has been proposed. To comprehensively evaluate GR expression in normal and tumorous tissues, a tissue microarray containing 18,570 samples from 147 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). GR positivity was found in 76.3% of 14,349 interpretable cancers, including 18.5% with weak, 19.6% with moderate, and 38.3% with strong positivity. GR positivity of at least a fraction of tumors was found in all 147 analyzed tumor types and at least one strongly GR positive tumor was found in 136 tumor types. 77 of our 147 tumor entities showed GR positivity of variable intensity in all analyzed cases. 43 further tumor entities showed GR positivity in 80-99.9% of cases. 21 tumor entities had a GR positivity rate between 50 and 80%, including urothelial carcinoma as well as gastric and esophageal adenocarcinoma. Only 6 tumor types had less than 50% GR positive. These included adenomas (21.7-32.5%), adenocarcinomas (17%) and neuroendocrine carcinomas (45.5%) of the colorectum. Reduced GR staining was significantly associated with adverse histopathological and clinical features in several tumor types. Low GR expression was linked to grade progression in pTa (p&amp;lt;0.0001) and to nodal metastasis in pT2-4 urothelial carcinoma of the urinary bladder (p=0.0051), advanced pT stage (p=0.0006) and estrogen receptor positivity (p=0.0126) in breast carcinomas of no special type (NST), as well as to high grade (p≤0.0076), advanced pT stage (p&amp;lt;0.0001), distant metastasis (p=0.0081), and poor overall survival (p=0.002) in clear cell renal cell carcinoma. GR expression was unrelated to clinic-pathological parameters in gastric, pancreatic, and colorectal adenocarcinoma as well as in serous high-grade carcinoma of the ovary. In summary, our data demonstrate frequent GR expression across all cancer types. Significant associations between reduced GR expression and unfavorable tumor features in some but not all tumor types suggest that the functional importance of GR regulated genes for cancer progression depends on the cell of tumor origin. Citation Format: Christina Tsourlakis, Frederike Wegener, Katharina Möller, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Guido Sauter, Andreas H. Marx, Ronald Simon, Till Krech, Christoph Fraune, Natalia Gorbokon, Maximilian Lennartz, Sarah Minner, Florian Viehweger. Abundant glucocorticoid receptor (GR) expression in human tumors: A tissue microarray study on more more than 18,000 tumors [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 2509.

The effect of race/ethnicity on cancer-specific mortality after trimodal therapy.

Trimodal therapy (TMT) is the most validated bladder-sparing treatment for organ-confined urothelial carcinoma of the urinary bladder (OC UCUB, namely cT2N0M0). However, it is unknown if barriers to the use of TMT or cancer-specific mortality (CSM) differences exist according to race/ethnicity. We addressed this knowledge gap. Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified OC UCUB patients aged from 18 to 85 treated with radical cystectomy (RC) or TMT. Temporal trends described TMT versus RC use over time. Subsequently, in the subgroup of TMT-treated patients, survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM according to race/ethnicity. Among 19,501 assessable patients, 15,336 (79%) underwent RC versus 4165 TMT (21%). Overall, of all races/ethnicities, 16,245 (83.3%) were White Americans, 1215 (6.3%) Hispanics, 1160 (5.9%) African Americans, and 881 (4.5%) Asian/Pacific Islanders. Among TMT-treated patients, 3460 (83.1%) were White Americans, 298 (7.1%) African Americans, 218 (5.3%) Hispanics, and 189 (4.5%) Asian/Pacific Islanders. The lowest rate of TMT use relative to RC and TMT patients was recorded in Hispanics (17.9%). Over time, TMT use increased in White Americans (EAPC: + 4.5%, p = 0.001) and Asians/Pacific Islanders (EAPC: + 5.2%, p = 0.003), but not in others. Kaplan-Meier analyses showed median CSM of 49months, 41months, and 34months and not reached in White Americans, Hispanics, African Americans, and Asian/Pacific Islanders, respectively (p = 0.02). In MCR models, two race/ethnicity subgroups independently predicted either worse (African Americans, HR: 1.20, p = 0.02) or better CSM (Asian/Pacific Islanders, HR: 0.75, p = 0.02). Race/ethnicity affects both access to TMT (lower access in Hispanics) as well as survival after TMT (better in Asians/Pacific Islanders and worse in African Americans).

Trimodal therapy effect on survival in urothelial vs non-urothelial bladder cancer.

To address cancer-specific mortality free-survival (CSM-FS) differences in patients with urothelial carcinoma of the urinary bladder (UCUB) vs non-UCUB who underwent trimodal therapy (TMT), according to organ confined (OC: T2N0M0) vs non-organ confined (NOC: T3-4NanyM0 or TanyN1-3M0) clinical stages. Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4N0-N3M0 bladder cancer treated with TMT, defined as the combination of transurethral resection of bladder tumour, chemotherapy, and radiotherapy. Temporal trends described TMT use over time. Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM in UCUB vs non-UCUB according to OC vs NOC stages. Of 5130 assessable TMT-treated patients, 425 (8%) harboured non-UCUB vs 4705 (92%) who had UCUB. The TMT rates increased for patients with OC UCUB from 92.4% to 96.8% (estimated annual percentage change of 0.4%, P < 0.001), but not in the NOC stages (P = 0.3). In the OC stage, the median CSM-FS was 36 months in patients with non-UCUB vs 60 months in those with UCUB, respectively (P = 0.01). Conversely, in the NOC stage, the median CSM-FS was 23 months both in UCUB and non-UCUB (P = 0.9). In the MCR models addressing OC stage, non-UCUB histology independently predicted higher CSM (hazard ratio 1.45, P = 0.004), but not in the NOC stage (P = 0.9). In OC UCUB, TMT rates have increased over time in a guideline-consistent fashion. Patients with OC non-UCUB treated with TMT showed a CSM disadvantage relative to OC UCUB. In the NOC stage, use of TMT resulted in dismal CSM, regardless of UCUB vs non-UCUB histology.

Diminution of Primary Cilia in the Stromal Cells at the Tumor-stromal Interface Correlates With an Aggressive Tumor Biology in the Urothelial Carcinoma of the Urinary Bladder.

Primary cilia (PC) are cellular organelles that regulate the cellular homeostasis. They are the seats of many oncogenic pathways and indirectly regulate the epithelial-mesenchymal transition (EMT) and extracellular matrix, both critical for the tumor microenvironment (TME). Though there are a few studies highlighting the alteration of PC in the tumor cells of various malignancies, none depict the PC in the stromal cells in the urothelial carcinoma of the urinary bladder (UC), the stromal cells being an essential component of TME. Therefore, we intend to evaluate the PC in the stromal cells at the tumor-stromal interface in UC. Immunohistochemistry for acetylated-α-tubulin (for PC), Ki67, E-cadherin, and SNAI1 was performed in 141 cases of UC and 5 normal controls, and primary cilium: nucleus (C:N) ratio was counted in the stromal cells at the tumor-stromal interface. The C:N ratio was correlated with various clinical and histopathological parameters. The C:N ratio showed significant diminution from normal control (mean=0.75) to low-grade UC (mean=0.24) ( P =0.001) to high-grade UC (mean value=0.17) ( P =0.001). There was a significant diminution of the C:N ratio from the noninvasive to invasive UC ( P =0.025). The C:N ratio did not show any correlation with EMT although negatively correlated with the Ki67 index ( r =-0.32; P =0.001), and a higher ratio showed a trend with a higher recurrence-free survival ( P =0.07). The diminution of the PC in the stromal cells at the tumor-stromal interface is an early event and correlates with an aggressive tumor biology of UC.

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.

Histomolecular classification of urothelial carcinoma of the urinary bladder : From histological phenotype to genotype and back

Of all urothelial carcinomas (UCs), 25% are muscle invasive and associated with a5-year overall survival rate of 50%. Findings regarding the molecular classification of muscle-invasive urothelial carcinomas (MIUCs) have not yet found their way into clinical practice. Prediction of molecular consensus subtypes in MIUCs with artificial intelligence (AI) based on histologic hematoxylin-eosin (HE) sections. Pathologic review and annotation of The Cancer Genome Atlas (TCGA) Bladder Cancer (BLCA) Cohort (N = 412) and the Dr. Senckenberg Institute of Pathology (SIP) BLCA Cohort (N = 181). An AI model for the prediction of molecular subtypes based on annotated histomorphology was trained. For afive-fold cross-validation with TCGA cases (N = 274), an internal TCGA test set (N = 18) and an external SIP test set (N = 27), we reached mean area under the receiver operating characteristic curve (AUROC) scores of 0.73, 0.8 and 0.75 for the classification of the used molecular subtypes "luminal", "basal/squamous" and "stroma-rich". By training on correlations to individual molecular subtypes, rather than training on one subtype assignment per case, the AI prediction of subtypes could be significantly improved. Follow-up studies with RNA extraction from various areas of AI-predicted molecular heterogeneity may improve molecular classifications and thereby AI algorithms trained on these classifications.

Immunohistochemical analysis on the role of gp130 in early-stage urothelial carcinoma of the urinary bladder

Immunohistochemical analysis on the role of gp130 in early-stage urothelial carcinoma of the urinary bladder

Pulmonary tumor embolism secondary to urothelial carcinoma of urinary bladder: case report and literature review

BackgroundTumor embolism is the least well-described cause of pulmonary embolism, taking into account the non-specificity of radiographic and nuclear imaging results, the necessity of anatomopathological evidence and the frequency of deep venous thrombosis in the course of solid tumors, suggesting thus thromboembolism.Case presentationWe report a rare case of urothelial carcinoma of the urinary bladder associated with persistent pulmonary embolism despite being on different anticoagulation regimens, the patient was ultimately found to have tumor thrombus in the pulmonary trunk secondary to tumoral extension. We provide a literature review as well about the diagnosis, evaluation and prognosis and of this rare clinical entity.ConclusionsOur case highlights the importance of keeping this unusual etiology in mind, particularly when faced with pulmonary embolism occurring in the context of a solid tumor and the ineffectiveness of various anticoagulation protocols. Furthermore, it emphasizes the pivotal role of cytology in confirming diagnosis and guiding therapy.

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.

Role of GATA3 in Early-Stage Urothelial Bladder Carcinoma Local Recurrence.

Background One of the most characteristic features of non-invasive urothelial carcinoma (UC) is its high recurrence rate. Guanine-adenine-thymine-adenine nucleotide sequence-binding protein 3 (GATA3), as a transcription factor, correlates with urothelial differentiation and has been reported with poor prognosis in high-grade UC and recurrence in breast malignancies. As such, we set out to study the specifics of GATA3 in non-invasive UC, emphasizing on prediction for recurrence. Methods The cohort comprised 163 patients, with a follow-up period of five years, including 109 pTa cases and 54 pT1 cases. Immunohistochemical expression of GATA3 was assessed using a histo score (H-score). Kaplan-Meier test was conducted for the time to recurrence, according to the level of expression of GATA3 and the indicators studied. Receiver operating characteristic (ROC) curve analysis was done to determine the role of accuracy and specificity of predictability of the indicators. Results Recurrence within the follow-up period was noted in 41.72% of cases. No recurrence relationship was established for age and gender. GATA3 expression showed a varying H-score. Using ROC curve analysis, a cut-off value of 155 divided UC expression levels into low and high, with a sensitivity of 72.7% and specificity of 78.7% (area under the curve=0.800, 95% confidence interval: 0.696-0.904, p<0.001), further showing an association between high levels of nuclear expression and risk of local recurrence (p<0.0001). Conclusion Herein we have described the sensitivity of high GATA3 expression in non-invasive UC of the urinary bladder and its relation to local recurrence, independent of gender, age, tumor differentiation, and stage.

Prehabilitation prior to radical cystectomy

Urothelial carcinoma of the urinary bladder places asignificant burden on the healthcare system in Germany, with 30,000 new cases annually. Radical cystectomy still remains the standard treatment for nonmetastatic, muscle invasive bladder cancer. Radical cystectomy represents the standard uro-oncologic procedure with the highest mortality. Due to the aging population, the number of elderly patients with urothelial carcinoma of the urinary bladder and reduced physical fitness and numerous comorbidities before the procedure is increasing. Prehabilitation before cystectomy aims to preoperatively identify patients at risk for postoperative complications and improve their physical condition. This includes conditioning and strength training, breathing exercises to improve lung capacity, and nutritional education. Studies on prehabilitation before various abdominal tumor surgeries have shown heterogeneous results so far. Positive effects have been shown for the improvement of functional parameters, but not for areduction of complications or mortality. Further research, especially in the German healthcare system, is needed to confirm the benefit of prehabilitation, for example, in cystectomy.

Regional differences in metastatic urothelial carcinoma of the urinary bladder patients across the United States SEER registries.

Despite advances in treatment, metastatic urothelial carcinoma of the urinary bladder (mUCUB) is associated with high mortality and treatment risk. We tested for regional differences in mUCUB within a large-scale, population-based database. Using the Surveillance, Epidemiology and End Results (SEER) database (2010-2018), patient (age, sex, race/ethnicity), tumor (T-stage, N-stage, number of metastatic sites), and treatment (systemic therapy, radical cystectomy) characteristics were tabulated for mUCUB patients according to 11 SEER registries. Multinomial regression models and multivariable Cox regression models tested overall mortality (OM), adjusting for patient, tumor and treatment characteristics. In 4817 mUCUB patients, registry-specific patient counts ranged from 1855 (38.5%) to 105 (2.2%). Important inter-regional differences existed for race/ethnicity (3-36% for others than non-Hispanic Whites), N-stage (28-39% for N1-3, 44-58% in N0, 8-22% for unknown N-stage), systemic therapy (38-54%) and radical cystectomy (3-11%). In multivariable analyses adjusting for these patient, tumor, and treatment characteristics, one registry exhibited significantly lower OM (SEER registry 10: hazard ratio [HR] 0.83) and two other registries exhibited significantly higher OM (SEER registries 9: HR 1.13; SEER registry 8: HR 1.24) relative to the largest reference registry (n=1855). We identified important regional differences that included patient, tumor, and treatment characteristics. Even after adjustment for these characteristics, important OM differences persisted, which may warrant more detailed investigation.

Immunohistochemical Expression of Estrogen Receptor Beta in Urothelial Carcinoma of the Urinary Bladder

Immunohistochemical Expression of Estrogen Receptor Beta in Urothelial Carcinoma of the Urinary Bladder

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.

A case of papillary and infiltrative urothelial carcinoma of the urinary bladder in a terrier dog

Urothelial carcinomas are malignant tumours originating from the epithelial layer of the urinary bladder. In this instance, a case of papillary and infiltrative urothelial carcinoma in the urinary bladder of a 2-year-old terrier dog was defined clinically, histopathologically and immunohistochemically. The material of the presented case consisted of urinary bladder tissue samples that were surgically extirpated from a two-year-old terrier-breed female dog that applied to the Department of Surgery of the Faculty of Veterinary Medicine, Selcuk University with the complaint of hematuria. The tumour brought to the pathology laboratory was 11*10*12 cm in size and had finger-shaped extensions. Its outer surface was rough and hemorrhagic. Tissues were fixed in 10% buffered formalin and paraffin blocks were obtained by going through the necessary routine follow-up procedures. Afterward, sections were taken and subjected to Hematoxylin-Eosin, Masson's Trichrome, and immunohistochemical staining. As a result of the pathological and immunohistochemical examinations of the tumoral tissue samples taken from the urinary bladder, the diagnosis of papillary and infiltrative urothelial carcinoma was reached, and the case was discussed with the information provided by the literature. In addition, immunohistochemically, intense Proliferating cell nuclear antigen (PCNA) and Vascular endothelial growth factor (VEGF) staining has been associated with malignancy.

Abstract 2212: Prevalence of PGP9.5 expression in human cancers: A TMA study of 14,900 tumors from 148 tumor types

Abstract The ubiquitin C-terminal hydrolase L1 (UCH-L1), also termed protein gene product 9.5 (PGP9.5) is an important component of the ubiquitination/deubiquitination system and plays a role in the posttranslational modification of proteins including protein degradation, relocation and change of function. Altered PGP9.5 expression has been suggested to play a role for resistance to chemotherapy, metastasis, and patient prognosis in several tumor entities. To comprehensively determine PGP9.5 expression in normal and neoplastic tissues, a tissue microarray containing 14,913 samples from 148 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. PGP9.5 immunostaining was found in 2,667 of 11,062 analyzed tumors and considered weak in 9.8%, moderate in 5.8% and strong in 8.5% of tumors. 113 of 148 tumor categories showed at least one positive case, and 90 of these tumor categories contained at least one case with strong PGP9.5 staining. PGP9.5 positivity was most seen in various types of neuronal and neuroendocrine neoplasms (71.1-100%), germ cell neoplasms of the testis (82.1%), and in mesotheliomas (74%). PGP9 positivity was seen in 14.2% of 606 clear cell and in 45.4% of 255 papillary renal cell carcinomas (RCC). In clear cell RCC, strong PGP9.5 staining was associated with high ISUP grade (p&amp;lt;0.0001), pT stage (p=0.0012), nodal (p=0.038) and distant metastasis (p&amp;lt;0.0001) as well as with a shortened overall, tumor specific and recurrence free survival (p&amp;lt;0.0001 each). In papillary RCC, strong PGP9.5 staining was significantly associated with high ISUP grade (p=0.009), advanced UICC stage (p=0.015), and shortened recurrence free survival (p&amp;lt;0.0001). In urothelial carcinoma of the urinary bladder, high PGP9.5 expression was associated with muscle-invasion (p&amp;lt;0.0001) but PGP9.5 immunostaining was unrelated to prognosis in pT2-4 carcinomas. In a joint analysis of 527 squamous cell carcinomas from 11 different sites of origin, PGP9.5 positivity was associated with high tumor grade (p=0.0021). PGP9.5 immunostaining was unrelated to pT and pN status in 207 serous high-grade and 82 endometrioid ovarian carcinoma, in 221 endometrioid endometrium cancer as well as in 292 papillary and in 89 follicular thyroid carcinomas. In ductal adenocarcinomas of the pancreas and in 356 gastric adenocarcinomas, PGP9.5 staining was unrelated to grade, pT and pN stage. Our data provide an overview on prevalence of PGP9.5 expression in cancer. PGP9.5 expression occurs commonly in many different tumor entities. PGP9.5 overexpression is strikingly linked to patient outcome in some tumor entities (i.e. clear cell RCC) but appears to be unrelated to unfavorable tumor characteristics in various other important tumor entities (i.e. gastric, pancreatic, ovarian cancer). Citation Format: Sekander Scherzai, Maximilian Lennartz, Frank Jacobsen, Florian Viehweger, David Dum, Anne Menz, Ria Uhlig, Andrea Hinsch, Doris Hoeflmayer, Christoph Fraune, Christian Bernreuther, Patrick Lebok, Soeren Weidemann, Guido Sauter, Till Sebastian Clauditz, Till Krech, Andreas H Marx, Ronald Simon, Stefan Steurer, Eike Burandt, Natalia Gorbokon, Sarah Minner. Prevalence of PGP9.5 expression in human cancers: A TMA study of 14,900 tumors from 148 tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2212.

ROLE OF P 53 AND KI-67 AS A PROGNOSTIC BIOMARKER OF UROTHELIAL CARCINOMA.

Introduction: Bladder cancers are common malignancies worldwide, and histological examination is the cornerstone of diagnosis and management of these tumours. There exists huge interobserver variability in grading of urothelial carcinoma, furthermore supercial biopsies and cautery effect also effect tumour staging. Pathological grading, staging and their correlation with molecular markers like p53 and Ki-67 might better predict patient outcome and play signicant role in designing the management protocols of these patients. Thus, we aimed to study the role of p 53 and Ki-67 as prognostic and diagnostic biomarkers of urothelial carcinoma in south east Indian population. This was a Methods: prospective study that included 46 patients with Urothelial carcinoma of the urinary bladder. The histopathological evaluation of the tumor tissue was performed to assess the grade and stage of the tumor and was further correlated with important demographic details and with immunohistochemical expression of p 53 and Ki-67. The mean age was 55 and 65 years Results: for male and female patients respectively. Haematuria was the most common presenting symptom. A total of 38 (74%) patients had high-grade tumors. p T2 stage disease was observed in 60% patients. High expression of p 53 expression was noted in 52% of total cases, of which 85% of cases had high grade morphology and 66% were p T2 stage tumours. High expression of p 53 was also noted in 45% of p T1 tumors. Ki-67 showed high expression in 82.6 % of cases; 94% of which were high-grade and 25% were low-grade cases. Although males have preponderance for Conclusion: afiction, but in our country, females also show higher incidence of urothelial carcinoma as compared to published literature. In addition, patients in Indian population present with higher stage disease. p 53 and Ki-67 are biomarkers of higher stage and grade disease, however additional factors also play a denite role in tumour progression and thus in patient outcome