scholarly journals Differential expression of NF-κB heterodimer RelA/p50 in human urothelial carcinoma

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5563 ◽  
Author(s):  
Sankari Durairajan ◽  
Charles Emmanuel Jebaraj Walter ◽  
Mary Divya Samuel ◽  
Dinesh Palani ◽  
Dicky John Davis G ◽  
...  

Background Urothelial carcinoma (UC) is the fifth most common malignancy that accounts for 5% of all cancers. Diagnostic markers that predict UC progressions are inadequate. NF-κB contributes towards disease progression upon constitutive activation in many solid tumors. The nuclear localization of NF-κB indicates increased transcriptional activity while cytoplasmic localization indicates the inactive protein repository that can be utilized readily by a malignant cell. This study delineates the nuclear and cytoplasmic differential expression of NF-κB heterodimers in UC progression. Methods The involvement of the NF-κB proteins in UC was analyzed in silico using cytoscape. The expression of NF-κB heterodimers was analyzed by immunohistochemistry. Results PINA4MS app in cytoscape revealed over expression of RelA and suppression of NF-κB1 (p50 precursor) in UC whereas the expression of NF-κB target proteins remained unhindered. Immunohistochemical localization showed nuclear RelA/p50 in low grade UC whereas in high grade only RelA expression was observed. Conversely, cytoplasmic expression of RelA/p50 remained extensive across high and low grade UC tissues (p < 0.005). RelA nuclear and cytoplasmic expression (p < 0.005) was directly proportional to the disease progression. In our study, some of the high-grade UC tissues with squamous differentiation and muscle invasion had extensive nuclear p50 localization. The phenomenon of RelA/p50 expression seen increased in low-grade UC than high grade UC might be due to their interaction with other members of NF-κB family of proteins. Thus, NF-κB RelA/p50 differential expression may play a unique role in UC pathogenesis and can serve as a biomarker for diagnosis.

2020 ◽  
pp. 1-4
Author(s):  
Nishat Ahmad ◽  
Saurabh Banerjee ◽  
A K. Srivastava

BACKGROUND: Urinary bladder cancer is second most common cancer after prostate cancer in the genitourinary system. Urothelial Carcinoma is the commonest tumour type accounting for 90% of all primary tumours of the bladder Histopathological analysis of cystoscopic bladder biopsy and Transurethral resection of the bladder tumour (TURBT) material are the mainstay for cancer diagnosis. This study was aimed to determine the frequency of different types of neoplastic lesions of the urinary bladder and to determine the grade and stage of urothelial tumours. MATERIAL METHOD: The study was carried out in the Department of Pathology, Rajendra Institute of Medical Sciences (RIMS), Ranchi from January 2018 to June 2020 and included 30 cases of cystoscopic biopsies and TURBT specimens. RESULTS: Out of 30 cases of neoplastic lesions, majority were of high grade papillary urothelial carcinoma (n=14, 46.67%) followed by low grade papillary urothelial carcinoma (n=9, 30%), 3 cases (10%) were of PUNLMP, 2 cases (6.66%) of papilloma and 1 (3.33%) case each of moderately differentiated squamous cell carcinoma and extra nodal NHL. The most common age group was 41-50 years and 51-60 years with 9 (30%) cases each. Muscle invasion was seen only in high grade papillary urothelial carcinomas. CONCLUSION: High-grade urothelial carcinomas with lamina propria and muscle invasion are the most common neoplastic lesion of urinary bladder with significant morbidity and mortality. Muscle invasion and grading, as per TNM staging, are valuable prognostic factors.


2018 ◽  
Vol 9 (6) ◽  
pp. 45-50
Author(s):  
Binita Goyal ◽  
Sheshagiri Rao ◽  
Rajina Sahi ◽  
Subechhya Jaiswal

Background: Urinary bladder cancer is an important cause of morbidity and mortality due to urological conditions. It is tenth most common cancer overall in both sexes. It is seventh most common cancer overall and second most common cancer of genitourinary tract in males. Ninety five percent of bladder tumors are epithelial and the rest are mesenchymal, of which majority are primary urothelial tumors. Urothelial tumors are classified into infiltrating urothelial carcinoma with its variants and non-invasive urothelial neoplasias. Tumor stage is the strongest prognostic parameter.Aims and Objectives: The current study was designed with an aim to elucidate the histologic pattern of bladder tumors and observe whether any association between histologic grade and muscle invasion exists.Materials and Methods: This descriptive study was carried out on 84 cases of urinary bladder tumors received in Department of Pathology, College of Medical Sciences and Teaching Hospital during a time period of 5 years from January 2012 to December 2016.Results: The mean ± SD of age of presentation was 63±13 years with a male female ratio 3.2:1. Ninety-five percent cases were primary epithelial tumors and 93% cases were of urothelial origin. Low grade papillary urothelial carcinoma was the most common urothelial tumor (40.5%) followed by high grade papillary urothelial carcinoma (34.5%). Some rare types like primary adenocarcinoma and small cell carcinoma were also seen in this study (1.2% each). Muscle invasion was significantly higher in high grade (66%) as compared to low grade papillary urothelial carcinoma (3%). Muscle tissue was absent in 8 (9.5%) cases.Conclusion: There is relationship of histologic grade with aggressiveness of tumor. Most of the high grade tumors are muscle invasive at presentation. Submission of muscle tissue is important for optimal patient management.Asian Journal of Medical Sciences Vol.9(6) 2018 45-50


2016 ◽  
Vol 6 (12) ◽  
pp. 1001-1004
Author(s):  
EP Shrestha ◽  
K Karmacharya

Background: Neoplastic and non-neoplastic urinary bladder lesions are the main reasons for morbidity and mortality throughout the world. Amongst these, urothelial carcinoma is a common primary tumor of urinary bladder (90%). The objective of this study is to determine the profile of various urothelial lesions received in Army Hospital within 5 years of period.Materials and methods: Five years retrospective study of cystoscopic biopsies and radical cystectomy specimens were carried out in Department of Pathology, Army hospital.Results: Out of 53 cystoscopic biopsies and radical cystectomy specimens, 42 were neoplastic and 11 were non neoplastic lesions. Thirty six urothelial carcinomas were observed out of which 20 were high grade urothelial carcinoma and 16 were low grade. Out of 20 high grade urothelial carcinoma, 17 had muscle invasion and 3 had invasion upto lamina propria. Of 16 low grade urothelial carcinoma, 12 were noninvasive, 2 had invasion upto lamina propria and 2 had muscle invasion. Papilloma was the commonest benign lesions found (7.1%) followed by papillary urothelial neoplasms of low malignant potential (PUNLMP) (2.4%) and hemangioma (2.4%).Conclusion: This article have highlighted upon the importance of histopathological study in evaluating urinary bladder lesions. Also, it has helped in determining that neoplastic lesions were more common than non-neoplastic lesions as seen in our study. A great majority of neoplastic lesions were of urothelial origin. Cystoscopic studies and biopsies help in early detection of bladder neoplasms and they form the mainstay of the diagnosis and follow up.


2017 ◽  
Vol 62 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Andrew A. Renshaw ◽  
Edwin W. Gould

Context: High-grade urothelial carcinoma (UC) cells have many appearances on urine cytology, but according to The Paris System, they can be easily distinguished from umbrella cells. Objective: We aimed to define the incidence and appearance of high-grade UC cells that resemble umbrella cells in Cytospin preparations on urine cytology. Results: Cytospin preparations from 331 cases with biopsy follow-up (230 benign/low-grade and 101 malignant [22 carcinoma in situ, 52 papillary, 19 invasive UC, 8 other] cases) were reviewed. A total of 18 cases with malignant cells resembling umbrella cells were identified (17.8% of the malignant cases) and were the only type of malignant cell in 3% of the cases. Two patterns were identified. Tumor cells were either identifiable by at least 20 abnormal cells which were large, had abundant cytoplasm but an elevated nuclear-to-cytoplasmic ratio, and markedly enlarged, round-to-elongated nucleoli, or else rare cells with abundant cytoplasm but obviously malignant nuclei. Cells without nucleoli or obviously malignant nuclei were not specific. Conclusions: Malignant cells resembling umbrella cells can be seen in up to 17% of urine cytology specimens.


Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 109
Author(s):  
Ilan Bejar ◽  
Jacob Rubinstein ◽  
Jacob Bejar ◽  
Edmond Sabo ◽  
Hilla K Sheffer ◽  
...  

Introduction: Our previous studies showed elevated levels of Semaphorin3a (Sema3A) in the urine of patients with urothelial cancer compared to healthy patients. The aim of this study was to analyze the extent of Sema3A expression in normal and malignant urothelial tissue using immune-staining microscopic and morphometric analysis. Materials and Methods: Fifty-seven paraffin-embedded bladder samples were retrieved from our pathology archive and analyzed: 14 samples of normal urothelium, 21 samples containing low-grade urothelial carcinoma, 13 samples of patients with high-grade urothelial carcinoma, 7 samples containing muscle invasive urothelial carcinoma, and 2 samples with pure urothelial carcinoma in situ. All samples were immunostained with anti Sema3A antibodies. The area of tissue stained with Sema3A and its intensity were analyzed using computerized morphometry and compared between the samples’ groups. Results: In normal bladder tissue, very light Sema3A staining was demonstrated on the mucosal basal layer and completely disappeared on the apical layer. In low-grade tumor samples, cells in the basal layer of the mucosa were also lightly stained with Sema3A, but Seama3A expression intensified upon moving apically, reaching its highest level on apical cells exfoliating to the urine. In high grade urothelial tumors, Seama3A staining was intense in the entire thickness of the mucosa. In samples containing carcinoma in situ, staining intensity was high and homogenous in all the neoplastic cells. Conclusions: Sema3A may be serve as a potential non-invasive marker of urothelial cancer.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1090
Author(s):  
Hassan Sadozai ◽  
Animesh Acharjee ◽  
Thomas Gruber ◽  
Beat Gloor ◽  
Eva Karamitopoulou

Tumor budding is associated with epithelial-mesenchymal transition and diminished survival in a number of cancer types including pancreatic ductal adenocarcinoma (PDAC). In this study, we dissect the immune landscapes of patients with high grade versus low grade tumor budding to determine the features associated with immune escape and disease progression in pancreatic cancer. We performed immunohistochemistry-based quantification of tumor-infiltrating leukocytes and tumor bud assessment in a cohort of n = 111 PDAC patients in a tissue microarray (TMA) format. Patients were divided based on the ITBCC categories of tumor budding as Low Grade (LG: categories 1 and 2) and High Grade (HG: category 3). Tumor budding numbers and tumor budding grade demonstrated a significant association with diminished overall survival (OS). HG cases exhibit notably reduced densities of stromal (S) and intratumoral (IT) T cells. HG cases also display lower M1 macrophages (S) and increased M2 macrophages (IT). These findings were validated using gene expression data from TCGA. A published tumor budding gene signature demonstrated a significant association with diminished survival in PDAC patients in TCGA. Immune-related gene expression revealed an immunosuppressive TME in PDAC cases with high expression of the budding signature. Our findings highlight a number of immune features that permit an improved understanding of disease progression and EMT in pancreatic cancer.


CytoJournal ◽  
2017 ◽  
Vol 14 ◽  
pp. 17 ◽  
Author(s):  
Theresa Long ◽  
Lester J. Layfield ◽  
Magda Esebua ◽  
Shellaine R. Frazier ◽  
D. Tamar Giorgadze ◽  
...  

Background: The Paris System for Reporting Urinary Cytology represents a significant improvement in classification of urinary specimens. The system acknowledges the difficulty in cytologically diagnosing low-grade urothelial carcinomas and has developed categories to deal with this issue. The system uses six categories: unsatisfactory, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells, suspicious for high-grade urothelial carcinoma, high-grade urothelial carcinoma, other malignancies and a seventh subcategory (low-grade urothelial neoplasm). Methods: Three hundred and fifty-seven urine specimens were independently reviewed by four cytopathologists unaware of the previous diagnoses. Each cytopathologist rendered a diagnosis according to the Paris System categories. Agreement was assessed using absolute agreement and weighted chance-corrected agreement (kappa). Disagreements were classified as low impact and high impact based on the potential impact of a misclassification on clinical management. Results: The average absolute agreement was 65% with an average expected agreement of 44%. The average chance-corrected agreement (kappa) was 0.32. Nine hundred and ninety-nine of 1902 comparisons between rater pairs were in agreement, but 12% of comparisons differed by two or more categories for the category NHGUC. Approximately 15% of the disagreements were classified as high clinical impact. Conclusions: Our findings indicated that the scheme recommended by the Paris System shows adequate precision for the category NHGUC, but the other categories demonstrated unacceptable interobserver variability. This low level of diagnostic precision may negatively impact the applicability of the Paris System for widespread clinical application.


2019 ◽  
Vol 26 (10) ◽  
pp. 1719-1723
Author(s):  
Rukhsana Parveen Samo ◽  
Asim Mehmood ◽  
Sana Kashif

Objectives: To determine the urothelial carcinoma and its association with age and gender. Study Design: Retrospective study. Setting: Pathology department of Liaquat university of Medical and Health Science. Period: One year from January 2016 to December 2016. Material and Methods: Four micrometer thick paraffin-embedded and formalin-fixed sections were prepared from transurethral resection6of bladder6tumor (TURBT) samples of urothelial carcinoma patients and were examined. Histological grading was categorized as low and high grades. All the data was collected by self-made proforma. Data was analyzed by SPSS version 20. Results: Total 83 cases were enrolled in current study; their mean age was 49.19+12.33 years. Males were found in the majority 51(61.4%) and females were 32(38.6%). Most common age group was 46-60 years 36(43.4%). According to the histological grading high grade was most common as 65.10%, and low grade urothelial carcinoma was 34.90%. There was no significant difference according to age of histological grading. Male gender was most common, while progression of disease was higher among females in contrast to males as high grade carcinoma was significantly higher among females, p-value 0.014. Conclusion: It was concluded that male gender is the contributing factor of urothelial carcinoma, but disease progression significantly high among females. No significant association has been found according to age.


2004 ◽  
Vol 63 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Christian Mawrin ◽  
Solveig Schulz ◽  
Steffen U. Pauli ◽  
Tim Treuheit ◽  
Sabine Diete ◽  
...  

2018 ◽  
Vol 104 (6) ◽  
pp. 451-458 ◽  
Author(s):  
Yu-Peng Wu ◽  
Yun-Zhi Lin ◽  
Min-Yi Lin ◽  
Ting-Ting Lin ◽  
Shao-Hao Chen ◽  
...  

Purpose: The aim of this work was to investigate the predictive factors for bladder cancer recurrence survival (BCRS) in patients with upper-tract urothelial carcinoma (UTUC). Methods: We selected patients with UTUC who underwent segmental ureterectomy (Su) or nephroureterectomy (Nu) from 2004 to 2013 from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with a history of intravesical therapy for bladder cancer and bladder cancer prior to the diagnosis of UTUC were excluded. We used Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards model to compare overall survival, cancer-specific survival, and BCRS. Results: In a cohort of 1,454 patients, 169 (11.6%) had low-grade tumors and 1,285 (88.4%) had high-grade tumors; 239 (16.4%) underwent Su and 1,215 (83.6%) underwent Nu. We found that T4 grade (hazard ratio [HR] = 6.216; 95% confidence interval [CI], 3.197-12.087) and ureteral tumors (HR = 1.764; 95% CI, 1.173-2.652) were predictors of shorter BCRS, whereas Nu (HR = 0.608; 95% CI, 0.388-0.953) predicted longer BCRS. Five-year BCRS rates were low-grade tumors: 94.1%, high-grade tumors: 85.4% (p = 0.038); plus Su: 82.9%, and Nu: 87.6% (p = 0.016). Conclusions: Use of Su should be more selective for high-grade tumors, as it correlates with shorter BCRS. Tumors located in the ureter are associated with shorter BCRS than those located in the renal pelvis.


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