Expression In Urothelial Carcinoma Research Articles

Fibroblast activation protein (FAP) expression in CK5/6 expressed (Basal subtype) & CK20 expressed (Luminal subtype) urothelial bladder carcinoma: an immunohistochemical study

ABSTRACT Urinary bladder cancer incidence varies all over the world. Egypt displays high incidence rates. Molecular subtyping helps risk stratification and personalized treatment. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment may provoke tumor-promotion or tumor suppression. Fibroblast activation protein (FAP) is a marker of CAFs, suggested to accelerate tumor progression in various cancers. In urothelial carcinoma, investigations regarding impact of FAP expression on prognosis are needed. This work aims to study impact of FAP expression in urothelial carcinoma and find its relation to CK 5/6 (basal) expressed and CK 20 (luminal) expressed immunohistochemical markers. This retrospective study included 70 urothelial carcinoma specimens. Immunohistochemistry was performed and results were analyzed. FAP was expressed in 67.1% of cases and showed significant association with advanced tumor stage, muscle invasion, mitoses in tumor cells and stratified groups; as 73.9% of FAP positive cases were of Ck5/6+/Ck20- (basal subtype). All studied parameters did not show significant association with patient’s overall survival. In conclusion, FAP could have a role in modulating tumor microenvironment and promoting tumor invasion. FAP is correlated with basal subtype of urothelial carcinoma, which may be an indicator of tumor aggressiveness. FAP antagonists may be helpful in preventing tumor progression.

Increased NUSAP1 expression is associated with lymph node metastasis and survival prognosis in bladder urothelial carcinoma

The main route of metastasis of bladder urothelial carcinoma is through lymph nodes; however, its exact mechanism remains unclear. In this study, we found an association of nucleolar and spindle associated protein 1 (NUSAP1) expression with BUC tissues along with lymph node metastasis and the survival prognosis. A total of 178 pathological specimens following radical bladder cancer resection were obtained. NUSAP1 expression was analyzed by immunohistochemistry. We evaluated the correlation between clinicopathological characteristics and NUSAP1 expression. Logistic regression was used to determine the independent variables that influenced lymph node metastasis. Uni- and multi-factorial Cox regression methods were used to determine the prognostic value of NUSAP1 expression in urothelial carcinoma of the bladder. High expression of NUSAP1 in BUC was not significantly related to the patient’s gender, age, or tumor number (p > 0.05), however was significantly associated with pathological grade, tumor diameter, pathological stage, and lymph node metastasis (p < 0.05). Lymph node metastasis was significantly correlated with pathological stage, pathological grade, tumor number, tumor diameter, and NUSAP1 expression (p < 0.05); only NUSAP1 expression was an independent predictor of lymph node metastasis in BUC (OR:1.786, 95% CI 1.229–2.596, p = 0.002). In addition, high NUSAP1 expression was an independent prognostic predictor for BUC. In BUC, NUSAP1 showed high expression and was significantly associated with lymph node metastasis, pathological stage, pathological grade, and tumor diameter. NUSAP1 was an independent predictor of lymph node metastasis and prognosis in BUC; higher expression indicated poorer prognosis of BUC patients.

The Immunohistochemical Expression of SOX-10 in Urothelial Carcinoma and the Non Neoplastic Urothelium; and a Correlation with the Tumor Features.

Objective:Evaluation of SOX-10 expression in malignant urothelial cells, comparing it with the phenotypically non neoplastic urothelium, and correlating it with the various clinicopathological variables, with a focus on the invasive pattern. Methods:Eighty paraffin blocks of urothelial carcinoma were stained by H&E. Histopathological features were evaluated and then immunostained with SOX-10 to evaluate its expression. Results:The evaluation of SOX-10 expression in urothelial carcinoma, revealed a high grade of SOX-10 expression in the malignant urothelium (43\\80 cases; 53.7%), while the adjacent the non neoplastic urothelium expressed high SOX-10 in (12\\42 case; 28.6%). Correlation of SOX-10 score with the various variables revealed a statistically significant correlation with the gross shape (P value=0.002), the tumor grade ((P value=0.009), the muscle invasion by the tumor ((P value=0.004), the tumor T stage, (P-value <0.001), N stage (P value=0.003), associated Schistoma hematobium infestation (P-value =0.016), and the presence of vascular tumor emboli (P-value =0.009). It was statistically insignificant with the gender, the anatomical site, and the perineural tumor invasion. Correlating the mean of SOX-10 score with some tumor features revealed a statistically significant correlation with the muscle invasion by the tumor, Tumor grade, T stage, and non neoplastic urothelium; P-value <0.001 each and N stage P value=0.006. Conclusion:SOX-10 is overexpressed in urothelial carcinoma and it was also detected in a significant part of the surrounding non neoplastic urothelium, which may contribute to understanding its role in multistep urothelial carcinogenesis as transcription or tumor-promoting factor, thus it could be used in future trials for specific targeted therapy.

The Prognostic Role of CDK9 in Bladder Cancer.

Simple SummaryIn this article, we investigated the prognostic role of cyclin-dependent kinase 9 expression in urothelial carcinoma. High CDK9 expression has recently been associated with shorter patient survival time, but its role in urothelial carcinoma has not yet been explored. The expression of CDK9 was higher in cancer than in normal urothelial tissue and correlated with tumor grade, stage, and invasiveness. To our surprise, patients with high CDK9 expression lived longer than patients with low CDK9 expression. In The Cancer Genome Atlas database cohort, high CDK9 RNA concentration correlates with longer survival of patients and CDK9 status remained a statistically significant prognostic factor in multivariate analysis. It seems that CDK9 not only regulates the expression of anti-apoptotic genes, leading to longer survival of cancer cells, it also facilitates DNA repair, preventing the build-up of genomic instability, crucial in the initiation and progression of bladder cancer. The results suggest that CDK9 overexpression is not always associated with a worse prognosis, while cell maturity and disease stage may influence the efficacy of potential targeted therapy.Introduction: Most patients with urothelial carcinoma are diagnosed with non-invasive tumors, but the prognosis worsens with the progression of the disease. Overexpression of cyclin-dependent kinase 9 has been recently linked to increased cancer proliferation, faster progression, and worse prognosis. However, some cancers seem to contradict this rule. In this work, we explored the prognostic role of CDK9 expression in urothelial carcinoma. Materials and Methods: We performed immunohistochemical analysis on 72 bladder cancer samples. To assess a larger group of patients, the Cancer Genome Atlas (TCGA) database containing 406 cases and transcriptomics information through the Human Pathology Atlas were analyzed. Results: CDK9 is overexpressed in urothelial cancer tissues when compared to normal urothelial tissues (p < 0.05). High CDK9 expression was observed in low-stage, low-grade, and non-muscle-invasive tumors (p < 0.05). The patients with high CDK9 expression had a significantly higher 5-year overall survival rate than those with low CDK9 expression (77.54% vs. 53.6% in the TMA group and 57.75% vs. 35.44% in the TCGA group, respectively) (p < 0.05). The results were consistent in both cohorts. Multivariate Cox regression analysis indicated that low CDK9 status was an independent predictor for poor prognosis in the TCGA cohort (HR 1.60, CL95% 1.1–2.33, p = 0.014). Conclusions: High CDK9 expression predicts a favorable prognosis in urothelial carcinoma and is associated with clinicopathological features characteristic for early-stage disease. The decrease in CDK9 expression can be associated with the build-up of genetic instability and may indicate a key role for CDK9 in the early stages of urothelial carcinoma.

Significance of Ki67, BCL 2 Immunoexpression in Urothelial Carcinoma and their Association with Grading and Staging: A Descriptive Cross-sectional Study

Introduction: Urinary bladder is the most common site of malignancy in the urinary tract and the most common type of cancer of urothelial origin is urothelial cell carcinoma. This subtype constitutes more than 90% of bladder cancer. Histological grade of tumour is one of the most important predictive parameter for prognosis and biological behavior of urothelial carcinoma. As some crucial discordances may arise between pathologists because of subjectivity, so immunohistochemistry can be used for accurate diagnosis and prediction of prognosis. Aim: To study the immununohistochemical expression of B-Cell Lymphoma 2 (BCL 2) and Ki(Kiel)-67 markers and their association with tumour grade and stage in urothelial carcinomas. Materials and Methods: A descriptive cross-sectional study was conducted in the Department of Pathology of a tertiary care R G Kar Medical College and Hospital, Kolkata, West Bengal, India. West Bengal, India, on a total of 75 cases from January 2018 to June 2019. The study population comprised of cases of urothelial lesions as diagnosed by cystoscopy, who underwent standardized operative procedures. Relevant sections were taken from different parts of the fixed specimens. Histopathological Examination (HPE) was done to confirm the presence or absence of non-invasive and invasive carcinoma, and the depth of invasive tumour cells for pathological staging. Evaluation of the level of cytological and architectural disorder at low and medium magnification (100X and 200X) were done for grading. Cytological disorder were defined as abnormalities in nuclear size, shape, and chromatin, while architectural disorder were defined as abnormalities in the orientation of the cells in relation to each other and to the basement membrane of the papillae. Immunohistochemical analysis was done for Ki67 and BCL 2 expression in paraffin embedded sections in all the cases. In this study, chi-square test was done with International Business Management(IBM) Statistical Package for Social Sciences (SPSS), as per which, the association between two variables is statistically significant if p value is &lt;0.05. Results: Out of total 75 cases(mean age: 67.3 years) analysed, 58 cases (77.3%) had Invasive type of bladder neoplasm, followed by low grade papillary urothelial carcinoma 10 (13.3%), and papillary urothelial neoplasm of low malignant potential 07 (9.3%). Ki67 expression in urothelial carcinoma has more significance because 59 cases (78.7%) showed high level expression (&gt;20%) out of 75 cases, whereas only 12 (16%) cases show high level expression (4+) of BCL 2 marker. Conclusion: Ki67 overexpression is seen more commonly, than BCL 2, in high grade tumours as well as in advanced stage. So Ki67 may be used as a marker to predict aggressive behavior and to differentiate low grade and high grade tumours also.

Expression of PD-L1 in Urothelial Carcinoma and its Association with Clinicopathological Parameters

Introduction: Urothelial cancer poses a substantial medical and public health challenge in most parts of the world. Programmed Death Ligand 1 (PD-L1) is a cell surface glycoprotein that plays an important role in the suppression of cellular immune responses to tumour and is now emerging as a new target for immunotherapy. Aim: To examine PD-L1 expression in urothelial carcinoma and its relationship with various clinicopathological parameters. Materials and Methods: A retrospective analysis study was conducted on 50 cases of Urothelial Carcinomas diagnosed in Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India from January 2016 to January 2019. Detailed clinical data of the patients’ was collected and the analysis was undertaken between February 2019 and April 2019. Tissues were formalin fixed, paraffin embedded and were studied for histopathological grading after staining with haematoxylin and eosin. All cases were subjected to immunohistochemistry for PD-L1 expression. Chi-square test was used to assess the relationship between PD-L1 positivity and various clinicopathological parameters. A p-value &lt;0.05 was considered as statistically significant. Results: A total of of 50 cases were included and 54% (27 cases out of total 50) were low grade cases. The maximum incidence was seen in 5th-7th decade of life with male preponderance. 27 cases out of the total 50 were low grade cases while the rest 46% (23 cases) were high grade. The PD-L1 positivity was observed in 19 cases (38%). The PD-L1 expression was significantly associated with high grade of tumour, increase in size of tumour and lamina propria invasion. Age, gender and muscle invasion however had no association with PD-L1 expression. Conclusion: The present study concluded that expression of PDL1 was significantly correlated with poorer clinicopathological variables including increasing size, higher grade and lamina propria invasion. PD-L1 positivity is therefore a bad prognostic marker

Predictive value of GATA3 and Ki-67 expression in biopsy and transurethral resection specimens in patients with urothelial carcinoma of the urinary bladder

Introduction/Objective. Urothelial carcinoma is the most commonly diagnosed malignancy of urinary bladder in clinical and pathohistological practice where various prognostic factors play a significant role. One of the most important pathohistological prognostic factors is the intensity of immunohistochemical staining. Among various immunohistochemical markers that have been proven to influence disease progression and the patient?s survival, role of Ki-67 and GATA3 in prediction of disease prognosis has not been completely clarified yet. The aim of this study was to determine the predictive value of GATA3 and Ki-67 mutual expression in urothelial carcinoma. Methods. Eighty patients were included in this study, out of which four groups were formed based on the pathological stage of urothelial carcinoma. After using preferred antibodies, their staining intensity was analyzed semiquantitatively. Results. Results showed that there was statistically significant correlation between the type of urothelial carcinoma, the pathological stage, and invasiveness and different grades of GATA3 expression, as well as statistically significant correlation between the type of urothelial carcinoma and the pathological stage and different grades of Ki-67 expression. The regression model showed low value of GATA3 and Ki-67 mutual expression. There was also statistical significance regarding the pathological stage and invasiveness of the tumor in survival analysis. Conclusion. Predictive value of GATA3 and Ki-67 mutual expression resulted as low from this study, but to our knowledge this was the first study to examine their predictive capability on biopsy and transurethral resection specimens.

Immunoexpression of PD-L1 and PD-1 and Its Clinicopathological Correlation in Urothelial Carcinomas.

Introduction Urothelial carcinomas are the most common types of bladder tumors that have recently shown a changing trend in treatment protocols with the introduction and approval of immune checkpoint inhibitors. The most important immune checkpoint lies with the PD-1–PD-L1 axis. Although multiple drugs have been approved, there is uncertainty about patient selection criteria and diagnostic assays. Recent studies related to the laboratory-developed tests have opened up the horizon of PD-1 and PD-L1 immunohistochemistry even at resource-constrained laboratories. We propose to study these immunohistochemistry markers in our laboratory using newer clones. Materials and Methods We selected 116 consecutive cases of transurethral bladder tumor resection from our laboratory archive and applied PD-1 and PD-L1 immunohistochemistry. The study was approved by the institution's ethics committee. Results We found high expression of PD-1 and PD-L1 in urothelial carcinoma even with different cut-offs of PD-L1. Muscle invasion, lamina invasion, and grade of carcinoma had a statistically significant effect on the expression; however, age and sex did not affect the expression. Conclusion Based on our current study, we can conclude that the clones used in our study show high expression in urothelial carcinoma and can aid in patient selection and treatment protocol, irrespective of age and sex.

Prognostic significance of EZH2 and ARID1A expression in urothelial carcinoma: an immunohistochemical study

ABSTRACT Enhancer of zeste homolog 2 (EZH2) and AT-rich interactive domain 1A (ARID1A) expression in urothelial carcinoma (UC) has not been well studied. ARID1A is a novel tumor suppressor gene coding for a chromatin remodeling protein that is mutated in urinary bladder cancer. The enhancer of zeste homolog 2 (EZH2) is a transcriptional repressor involved in gene silencing. Amplification of EZH2 has been reported in several malignancies. This study analyzed the immunohistochemical expression of EZH2 and ARID1A in 56 cases of UC that included (n = 21) cases of radical cystectomy and (n = 35) cases of transurethral resections of bladder tumor (TURBT) with muscle fibers and immunotherapy with adjuvant intravesical bacillus Calmette-Guerin (BCG). The predicting role of both markers for tumor recurrence and recurrence-free survival (RFS) was also analyzed. High EZH2 marker expression was observed in 75% of cases while 78.6% of cases had low ARID1A marker expression. There was a significant negative correlation between the two markers where high EZH2 and low ARID1A expression was significantly associated with higher tumor grade, stage, presence of muscle invasion, lymph node metastasis, presence of concomitant carcinoma in situ (CIS) and higher incidence of recurrence with shorter RFS rate. It was concluded that EZH2 and ARID1A play a role in tumor carcinogenesis and differentiation and could be considered as independent prognostic factors in UC and for use as a potential therapeutic target.

PD-L1 Tumor Cell Expression in Upper Tract Urothelial Carcinomas is Associated With Higher Pathologic Stage.

Upper tract urothelial carcinomas (UTUCs) are a rare and unique subset of urothelial carcinoma (UC). Patients with UTUC may qualify for treatment with immune checkpoint inhibitors if their tumor cells express programmed death ligand-1 (PD-L1). While several large studies have looked at PD-L1 expression in UC, most have not investigated UTUC as a separate group, and most have not used Food and Drug Administration approved PD-L1 stains and scoring systems. Moreover, comparison between studies of PD-L1 expression is challenging as a wide variety of different PD-L1 antibody clones, testing platforms, and cutoff values have been used in the literature. This is a retrospective study of 37 cases of resected UTUC. Representative tissue from each case was compiled into tissue microarrays and immunohistochemical stains for PD-L1 (Dako antibody clones 22C3 and 28-8) were performed. PD-L1 staining was evaluated using several established Food and Drug Administration approved scoring systems: tumor proportion score (TPS), combined positive score, and immune cell score. Associations between PD-L1 expression and clinicopathologic features were investigated. Overall expression of PD-L1 in UTUC was 29.7% when using a TPS cutoff of ≥1%. Total of, 55.6% of cases with higher pathologic stage (pT3 or pT4) were positive for PD-L1, compared with only 5.3% of cases with lower pathologic stage (pTis, pT1, or pT2; P=0.0011). When using a combined positive score cutoff of ≥10, there was no significant association between tumor stage and PD-L1 expression. There was no association between PD-L1 positivity and tumor grade, tumor location, sex, or age. There was 100% concordance between 22C3 and 28-8 in terms of positivity rate. Our study using approved testing methods shows that PD-L1 expression in UTUC is more often associated with high pathologic stage, which may reflect an immune response evasion mechanism that UC cells acquire later in disease progression. In addition we show that 29.7% of UTUCs are positive for PD-L1 TPS expression, comparable to the 20% to 30% reported in UC literature. Finally, PD-L1 22C3 and 28-8 clones show similar overall patterns of staining in this setting.

GATA3 and CK5/6 Immunohistochemical Expression in Urothelial Carcinoma: Diagnostic, Biological and Prognostic Significance

Background: Urothelial carcinomas [UCs] can be diagnostically challenging, particularly transurethral bladder tumors resection biopsies with limited material. Immunohistochemistry is a valuable instrument for diagnosis when morphology alone is inadequate. GATA-binding protein 3 [GATA3] and cytokeratin 5/6 [CK 5/6] contributes to the growth of UC. However, their correlative expression in UC and prognostic value has not been sufficiently investigated. The aim of the work: The current study aimed to evaluate the utility of GATA3 expression in UC and correlate that with CK 5/6 expression to verify different subtypes of UC and assess their prognostic significance. Methodology: Here, we immunohistochemically stained GATA3 and CK 5/6 in 90 UCs samples by transurethral bladder tumor resection in a retrospective study, between May 2018 and February 2020. All were histopathologically evaluated and immunohistochemically stained for GATA3 and CK 5/6, and then correlated them with the clinicopathological parameters to investigate their clinical significance. Results: GATA3 expression was seen in 76 patients [84.44 %]. There was significant correlation between GATA3 expression with the tumor histological grade and degree muscle invasion. There was a weak or even negative expression in high‑grade, invasive than the low‑grade, non-invasive tumor [P= <0.001]. CK5/6 was positive and focally positive in 27.78% with a significant correlation of CK5/6 expression with tumor grade and muscularis propria invasion. On the other side, tumors with diffuse GATA3 expression had low CK5/6 expression. Conclusion: GATA3 and CK 5/6 should be used as sensitive and specific markers for UC. They can also be effectively used in the prediction of probable grade and tumor invasion in biopsied material with poor morphological characters; and thus, help in the future appropriate treatment.

English

BACKGROUND Human epidermal growth factor receptor-2 HER2 / neu, is a trans membrane tyrosine kinase receptor of epidermal growth factor receptor (EGFR) family and is involved in the pathogenesis of urinary bladder cancer. In this study we attempted to evaluate the HER2 / neu expression in urothelial carcinoma of bladder and its association with tumour grading. METHODS This was a cross sectional study with a sample size of 75. Routine 4 micrometre thick sections of formalin fixed paraffin embedded tissue blocks stained with haematoxylin &amp; eosin were reviewed. Tumour grade was determined by using the World Health Organization (WHO) / International Society of Urological Pathologist criteria (ISUP). Immunohistochemistry was done by using HER2 / neu monoclonal antibody and its expression were observed. The membrane staining intensity and pattern were studied and scored. RESULTS In our study 75 cases of urothelial carcinoma were studied, of which 49 cases were papillary urothelial carcinoma low grade, 26 cases were papillary urothelial carcinoma high grade. Among these, 19 cases were infiltrating urothelial carcinoma. HER2 / neu positivity were observed in 27 (36 %) cases and overexpression in 8 (10 %) cases. Low grade urothelial carcinoma showed HER2 / neu positivity in 11 (22 %) cases and overexpression in 1 (2 %) case. High grade urothelial carcinoma showed HER2 / neu positivity in 16 (64 %) cases, among which 7 (28 %) cases showed overexpression. HER2 / neu positivity was seen in 13 (68 %) cases of infiltrating urothelial carcinoma with 4 (21 %) cases showing overexpression. A statistically significant difference in HER2 / neu expression was noted in high grade and invasive urothelial carcinoma compared to low grade and non-invasive urothelial carcinoma. CONCLUSIONS Urothelial carcinomas show overexpression of HER2 / neu and this over expression increases with increasing grade of tumour and muscle invasiveness. KEYWORDS Urothelial Carcinoma, HER2 / neu, Overexpression, Tumour Grade, Trastuzumab

Reduced Expression Level of GPX2 in T1 Bladder Cancer and its Role in Early-phase Invasion of Bladder Cancer

The role of glutathione peroxidase 2 (GPX2) expression in urothelial carcinoma (UC) is rarely reported. The aim of this study was to assess the expression status of GPX2 in UC of the bladder. We collected samples from 112 patients treated with radical cystectomy for immunohistochemical study. Following immunohistochemical analysis of the specimens, 86 (76.8%) had weak GPX2 expression. In cases with consistent GPX2 expression within the same lesion, the levels of GPX2 showed significant decreases from pTa to pT1 (47.1%) compared to those from pT1 to pT2 (5.9%) (p=0.017). Specimens obtained with transurethral resection before cancer progressed to muscle invasive bladder cancer showed that pT1 had a lower expression for GPX2 than that of pTa (63.3% vs. 93.3%; p=0.009). The decrease in GPX2 expression among those with UC of the bladder may be involved in the early step of cancer invasion.

RNA-binding proteins RBM-HuR, RBM3 and PODXL expression in urothelial carcinoma of the urinary bladder. Prognostic and clinical implications.

Aim of the studyThe clinical significance and predictive and prognostic value of HuR, RBM3, and PODXL expression in patients with urothelial bladder cancer (UBC) are not clear yet. The aim of this study was to assess HuR, RBM3 and PODXL expression in muscle invasive and non-muscle invasive UBC tissues, and to investigate the clinicopathological correlations and their predictive and prognostic impact in patients with such type of cancer.Material and methodsRBM-HuR, RBM3 and PODXL expression levels were evaluated in 70 patients with urothelial carcinoma by immunohistochemistry. The relationships between their expression, clinicopathological findings and prognostic data were analyzed.ResultsHigh RBM-HuR expression was related to muscle invasion (p = 0.008), metastasis to lymph nodes (p = 0.007), and presence of blood spread (p = 0.049). High RBM3 expression was associated with lower grade (p = 0.044), absence of distant metastasis (p = 0.025), and absence of lymph node metastasis (p = 0.018). High PODXL expression was significantly associated with advanced tumor stage (p < 0.001), larger tumor size (p = 0.050), lymphovascular invasion (p = 0.006), lymph node metastasis (p = 0.008), higher grade (p = 0.043) and distant metastasis (p = 0.002).Three-year overall survival rate was negatively associated with high expression of both RBM-HuR and PODXL while it was directly correlated with high expression of RBM3 (p = 0.008, 0.009 and 0.015 respectively). High RBM-HuR and PODXL expression and low expression of RBM3 were related to tumor recurrence (p = 0.022, 0.011 and 0.015).ConclusionsRBM-HuR and PODXL expressions are markers of poor prognosis while RBM3 is a good prognostic marker for urothelial carcinoma of the bladder.

Androgen receptor expression in the urinary bladder urothelial carcinoma and its relation to known prognostic factors

Objective: The current study was carried out to assess the prognostic value of androgen receptor expression in urothelial carcinoma of the bladder and correlate it to the disease outcome.Methods: Histologically confirmed cases of bladder urothelial carcinoma were studied. Clinical, pathological, and radiological data were collected. Paraffin embedded tissue sections were submitted for hematoxylin and eosin staining, as well as immunohistochemical staining for androgen receptor in tumor cells.Results: Nuclear androgen receptor expression was positive in 75% of the studied histopathological specimens. Additionally, a significant positive association between androgen receptor expression and tumor grade, muscle invasion &amp; tumor size were noticed.Conclusions: There is a significant association between large tumor size, high grade, deep invasion, and expression of Androgen receptor in urothelial bladder carcinoma. Antiandrogen could be an effective chemo preventive or therapeutic approach in treatment of urothelial bladder carcinoma.

Programmed Cell Death-Ligand 1 Expression Status in Urothelial Carcinoma According to Clinical and Pathological Factors: A Multi-Institutional Retrospective Study.

Purpose: To investigate programmed cell death-ligand 1 (PD-L1) expression status and the clinical and pathological factors related to its expression in urothelial carcinoma (UC) patients.Materials and Methods: Data from 761 UC patients who underwent testing for PD-L1 expression using the VENTANA (SP-142 immunohistochemistry assay) for measuring PD-L1 expression according to the manufacturer's protocol between February 2016 and July 2019 were retrospectively reviewed. Patients were categorized into three groups based on the percentage of tumor area covered by PD-L1-expressing tumor-infiltrating immune cells (ICs) as follows: IC0 (<1%), IC1 (≥1% and <5%), and IC2/3 (≥5%). Positive PD-L1 expression was defined as IC2/3 (≥5%). The factors related to positive PD-L1 expression were assessed by using unadjusted and adjusted logistic regression analyses.Results: In the entire cohort, 213 (28%) patients showed positive PD-L1 expression. Final adjusted regression analyses for positive PD-L1 expression revealed that several factors, including intravesical BCG prior to PD-L1 testing (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.37–0.96), advanced tumor stage (stage III/IV) (OR 2.04, 95% CI 1.41–2.93), and high tumor grade (OR 5.31, 95% CI 2.38–11.83) were significantly associated with positive PD-L1 expression.Conclusions: This study showed that the PD-L1 expression is associated with several clinical and pathological factors for the first time in a real-world setting. Further follow-up clinical trials should consider adjusting these factors, including intravesical BCG treatment, tumor stage and grade to clarify the utility of PD-L1 as a biomarker.

SALL4 Expression in Urothelial Carcinoma of Urinary Bladder; a Tissue Microarray Analysis

Sal-like protein 4 (SALL4) is a cellular pluripotent embryonic nuclear factor that has been a useful immunohistochemistry marker for germ-cell tumors. Our understanding of SALL4 expression in other human body malignancies remains limited. The diagnostic value of SALL4 expression as an independent diagnostic marker for patients with bladder urothelial carcinoma remains unclear. The aim of this study is to investigate the relation of SALL4 immunostaining in urinary bladder urothelial carcinoma and normal bladder urothelial tissue with clinicopathological diagnostic parameters. Material and methods: Three hundred and seventy cases of bladder urothelial carcinomas and 22 non-neoplastic bladder urothelial tissues were obtained from the Department of Pathology at King Abdulaziz University Jeddah, Saudi Arabia. Tissue microarrays were constructed. Tissue sections were stained using anti-human SALL4 monoclonal antibody. The immunostaining results were recorded and analyzed. Results: SALL4 exhibited weak nuclear expression in only 6 out of 370 cases of bladder urothelial carcinomas (1.6%). All the SALL4-positive cases were high-grade tumors. Normal urothelial tissues were all completely negative. SALL4 immunostaining revealed no association with gender, age, tumor invasiveness, stage, lymphovascular invasion, regional lymph node metastasis, or distant metastasis. Conclusion: SALL4 is rarely expressed in bladder urothelial carcinoma and is typically limited to high-grade tumors. However, this immunoexpression must be kept in mind when applying SALL4 antibody for differentiating urothelial carcinomas from germ-cell tumors and when assessing metastatic poorly differentiated tumors of unknown origin.

Assessing CD 10 Expression Level and Its Prognostic Impact in Egyptian Patients with Urothelial Carcinoma.

Background and aim:CD10 is expressed in urothelial carcinoma cells and cancer associated fibroblasts (CAF). In the current study, CD10 immunohistochemical staining (IHC) and CD10 mRNA expression in urothelial carcinoma of bladder (UCB) were assessed, and its relationship with tumor progression and prognosis was investigated. Patients and Methods:In this study, 106 formalin fixed paraffin-embedded (FFPE) tissue of UCB, obtained through radical cystectomy specimen, and 10 matched normal tissue samples were included.CD10 expression was evaluated by immunohistochemistry and real time PCR techniques. Results:CD10 expression in tumor cells and associated stromal fibroblasts was significantly associated with high tumor grade and advanced stage. Significant correlation was found between CD10 tumor expression and lymphovascular invasion (LVI) (P<0.001) as well as perineural invasion (PNI). CD10 expression in stromal fibroblasts was significantly associated with squamous differentiation of tumor cells, lymph node metastasis (LNM), and tumor necrosis. Positive CD10 expression in both tumor cells and associated stromal fibroblasts was associated with shorter OS . CD10 mRNA was overexpressed in tumors in comparison with the matched normal tissues. CD10 mRNA was significantly higher in invasive tumor, advanced stage tumor, and high grade tumor. There was significant correlation between CD10 mRNA tumor expression and LVI, PNI, and tumor recurrence. Conclusion:Increased expression of CD10 in the tumor and CAF was strongly correlated with tumor progression, invasion, metastasis, shorter OS, and RFS in urothelial carcinoma patients. CD10 mRNA showed significantly higher expression in tumor tissue than in matched normal tissue. CD10 mRNA was associated with depth of invasion, TNM stage, tumor grade, vascular tumor invasion, and tumor recurrence.

Differential Expression and Clinicopathological Significance of HER2, Indoleamine 2,3-Dioxygenase and PD-L1 in Urothelial Carcinoma of the Bladder.

Purpose: Evasion of the immune system by cancer cells allows for the progression of tumors. Antitumor immunotherapy has shown remarkable effects in a diverse range of cancers. The aim of this study was to determine the clinicopathological significance of human epidermal growth factor receptor 2 (HER2), indoleamine 2,3-dioxygenase (IDO), and programmed death ligand-1 (PD-L1) expression in urothelial carcinoma of the bladder (UCB). Materials and Methods: We retrospectively studied 97 patients with UCB. We performed an immunohistochemical study to measure the expression levels of HER2, IDO, and PD-L1 in UCB tissue from these 97 patients. Results: In all 97 cases, the PD-L1 expression of tumor-infiltrating immune cells (ICs) was significantly correlated with higher pathologic tumor stage (pT). In pT2–pT4 cases (n = 69), higher levels of HER2 and IDO expression in invasive tumor cells (TCs) were associated with shorter periods of disease-free survival (DFS). Conclusion: These results imply that the expression of PD-L1 in ICs of the UCB microenvironment is associated with cancer invasion and the expression of HER2 or IDO in the invasive cancer cell and suggestive of the potential for cancer recurrence. We suggest that the expression levels of IDO, HER2, and PD-L1 could be useful as targets in the development of combined cancer immunotherapeutic strategies.

Staining pattern and intensity of CD10 expression in Urothelial carcinoma and its prognostic significanc

Abstract Introduction: Urinary bladder cancer is common malignancy of the genitourinary tract in both males and females.CD10 is cell surface zinc dependent metalloprotease which may play a crucial role in tumor progression, invasion and metastasis. The present study was done to analyze staining pattern and intensity of CD10 and its association with grade, stage and prognosis of urothelial carcinoma. Materials and Methods: The prospective study included 51 cases of urothelial carcinoma over a period of one year which were followed up for three years. The staining pattern and intensity of CD10 immunostaining was correlated with histopathological grade, stage and survival of these patients. Results: The maximum number of urothelial carcinoma cases (33.3%) were in the age group of 60-70 years with mean age of 60.4 years. The staining pattern and intensity of CD10 showed statistical significant increase with increase of histopathological grade, stage of tumor and with decrease of survival of patients (p Conclusion: The study concludes that there is significant association between staining intensity and score of CD10 immuno-expression with histopathological grade, stage and the survival in patients of urothelial carcinoma.The staining intensity and pattern of CD10 immuno-expression may be helpful in determination of prognosis of urothelial carcinoma cases. In addition, it is suggested that further larger studies with extended follow ups may be done to evaluate the exact role of CD10 in prognosis of urothelial carcinoma. Keywords: Urothelial carcinoma, CD10, Histopathological grade, Stage, Survival, Prognosis. Introduction Urinary bladder cancer represents the common and frequent malignancy of the genitourinary tract in both males and females. Globally the incidence of bladder cancer is 3.1% with the mortality of about 2% and age standardized rate is of 5.3/100000 population.[1]In India the incidence of bladder cancer is 1.6% with the mortality o