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Journal of Hematology & Oncology Jun 2022Urothelial carcinoma (UC) is the most common pathological type of bladder cancer, a malignant tumor. However, an integrated multi-omics analysis of the Chinese UC...
BACKGROUND
Urothelial carcinoma (UC) is the most common pathological type of bladder cancer, a malignant tumor. However, an integrated multi-omics analysis of the Chinese UC patient cohort is lacking.
METHODS
We performed an integrated multi-omics analysis, including whole-exome sequencing, RNA-seq, proteomic, and phosphoproteomic analysis of 116 Chinese UC patients, comprising 45 non-muscle-invasive bladder cancer patients (NMIBCs) and 71 muscle-invasive bladder cancer patients (MIBCs).
RESULT
Proteogenomic integration analysis indicated that SND1 and CDK5 amplifications on chromosome 7q were associated with the activation of STAT3, which was relevant to tumor proliferation. Chromosome 5p gain in NMIBC patients was a high-risk factor, through modulating actin cytoskeleton implicating in tumor cells invasion. Phosphoproteomic analysis of tumors and morphologically normal human urothelium produced UC-associated activated kinases, including CDK1 and PRKDC. Proteomic analysis identified three groups, U-I, U-II, and U-III, reflecting distinct clinical prognosis and molecular signatures. Immune subtypes of UC tumors revealed a complex immune landscape and suggested the amplification of TRAF2 related to the increased expression of PD-L1. Additionally, increased GARS, related to subtype U-II, was validated to promote pentose phosphate pathway by inhibiting activities of PGK1 and PKM2.
CONCLUSIONS
This study provides a valuable resource for researchers and clinicians to further identify molecular pathogenesis and therapeutic opportunities in urothelial carcinoma of the bladder.
Topics: Biomarkers, Tumor; Carcinoma, Transitional Cell; Endonucleases; Humans; Proteogenomics; Proteomics; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35659036
DOI: 10.1186/s13045-022-01291-7 -
International Journal of Molecular... Aug 2023Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The... (Review)
Review
Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection involves surveillance, intravesical therapy, and cytology with cystoscopy. Urinary cytology, cystoscopy, and radiological evaluation of the upper urinary tract are recommended during follow-up in the international urological guidelines. Cystoscopy is the standard examination for the first assessment and follow-up of NMIBC, and urine cytology is a widely used urinary test with high sensitivity for high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). In recent years, various urinary assays, including DNA methylation markers, have been used to detect bladder tumors. Among these, the Bladder EpiCheck test is one of the most widely used and is based on analysis of the methylation profile of urothelial cells to detect bladder neoplasms. This review assesses the importance of methylation analysis and the Bladder EpiCheck test as urinary biomarkers for diagnosing urothelial carcinomas in patients in follow-up for NMIBC, helping cytology and cystoscopy in doubtful cases. A combined approach of cytology and methylation analysis is suggested not only to diagnose HGUC, but also to predict clinical and histological recurrences.
Topics: Humans; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urinary Bladder; Cystoscopy; Epithelial Cells; Urine
PubMed: 37569864
DOI: 10.3390/ijms241512489 -
Virchows Archiv : An International... May 2022The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to...
The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to conventional urothelial carcinoma. The clinicopathological features of 104 HGT1 cases of urothelial carcinoma of the bladder with variant histology present in 34 (37%) were assessed. The endpoint of the study was disease-free survival and cancer-specific survival. Overall, variant histology was identified as a significant predictor of disease-free survival (P = 0.035). The presence of any specific variant histology (squamous, glandular, micropapillary, nested, microcystic, inverted growth, villous-like, basaloid, and lymphoepithelioma-like) was identified as a significant predictor of disease-free survival (P = 0.008) and cancer-specific survival (P = 0.0001) in HGT1 bladder cancer. Therefore, our results support including micropapillary HGT1 urothelial carcinoma within the aggressive high-risk category, as suggested by some recent clinical guidelines, but also favor nested, glandular, and basaloid to be placed in the high-risk category due to their potential of aggressive, life-threatening behavior and their limited response to bacillus Calmette-Guerin therapy. Conversely, the low-risk category would include urothelial carcinomas with squamous, inverted growth, or microcystic morphology, all with limited life-threatening potential and good response to current therapy. A very low-risk category would finally include patients whose tumors present villous-like or lymphoepithelioma-like morphology. In conclusion, our findings support the value of reporting the variant histology as a feature of variable aggressiveness in HGT1 urothelial carcinoma of the bladder.
Topics: Carcinoma, Papillary; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Female; Humans; Male; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35122124
DOI: 10.1007/s00428-021-03264-6 -
Annals of Diagnostic Pathology Aug 2022Preoperative diagnosis in liquid-based cytology preparation in voided urine specimen and cyto-histologic correlation of small cell carcinoma of the urinary bladder has... (Review)
Review
Preoperative diagnosis in liquid-based cytology preparation in voided urine specimen and cyto-histologic correlation of small cell carcinoma of the urinary bladder has not been described in detail in the literature. A 79-year old male presented at our institution with gross hematuria. He was accurately diagnosed with small cell carcinoma of the bladder on liquid-based cytology in urine. The patient subsequently proceeded to transurethral resection of the bladder tumor, confirming the diagnosis. In this article, we present a detailed report of primary urothelial carcinoma with dominant neuroendocrine differentiation of the bladder describing the cytologic and histologic morphologic features, its differential diagnosis with a review of the literature.
Topics: Aged; Carcinoma, Small Cell; Carcinoma, Transitional Cell; Cytodiagnosis; Humans; Male; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35427925
DOI: 10.1016/j.anndiagpath.2022.151947 -
The American Journal of Surgical... Jan 2024The 2022 International Society of Urological Pathology (ISUP) Consensus Conference on Urinary Bladder Cancer Working Group 2 was tasked to provide evidence-based...
International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer. Working Group 2: Grading of Mixed Grade, Invasive Urothelial Carcinoma Including Histologic Subtypes and Divergent Differentiations, and Non-Urothelial Carcinomas.
The 2022 International Society of Urological Pathology (ISUP) Consensus Conference on Urinary Bladder Cancer Working Group 2 was tasked to provide evidence-based proposals on the applications of grading in noninvasive urothelial carcinoma with mixed grades, invasive urothelial carcinoma including subtypes (variants) and divergent differentiations, and in pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component. By 2004 WHO grading, the vast majority of lamina propria-invasive (T1) urothelial carcinomas are high-grade, and the rare invasive low-grade tumors show only limited superficial invasion. While by 1973 WHO grading, the vast majority of T1 urothelial carcinomas are G2 and G3 and show significant differences in outcome based on tumor grade. No consensus was reached if T1 tumors should be graded either by the 2004 WHO system or by the 1973 WHO system. Because of the concern for underdiagnosis and underreporting with potential undertreatment, participants unanimously recommended that the presence of urothelial carcinoma subtypes and divergent differentiations should be reported. There was consensus that the extent of these subtypes and divergent differentiations should also be documented in biopsy, transurethral resection, and cystectomy specimens. Any distinct subtype and divergent differentiation should be diagnosed without a threshold cutoff, and each type should be enumerated in tumors with combined morphologies. The participants agreed that all subtypes and divergent differentiations should be considered high-grade according to the 2004 WHO grading system. However, participants strongly acknowledged that subtypes and divergent differentiations should not be considered as a homogenous group in terms of behavior. Thus, future studies should focus on individual subtypes and divergent differentiations rather than lumping these different entities into a single clinicopathological group. Likewise, clinical recommendations should pay attention to the potential heterogeneity of subtypes and divergent differentiations in terms of behavior and response to therapy. There was consensus that invasive pure squamous cell carcinoma and pure adenocarcinoma of the bladder should be graded according to the degree of differentiation. In conclusion, this summary of the International Society of Urological Pathology Working Group 2 proceedings addresses some of the issues on grading beyond its traditional application, including for papillary urothelial carcinomas with mixed grades and with invasive components. Reporting of subtypes and divergent differentiation is also addressed in detail, acknowledging their role in risk stratification. This report could serve as a guide for best practices and may advise future research and proposals on the prognostication of these tumors.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Urinary Bladder; Carcinoma, Squamous Cell; Carcinoma in Situ; Neoplasm Grading
PubMed: 37382156
DOI: 10.1097/PAS.0000000000002077 -
Emerging roles of autophagy in the development and treatment of urothelial carcinoma of the bladder.Expert Opinion on Therapeutic Targets Sep 2021High recurrence rates, frequent surveillance strategies, and current multidisciplinary treatment approaches make urothelial carcinoma of bladder (UCB) one of the most... (Review)
Review
INTRODUCTION
High recurrence rates, frequent surveillance strategies, and current multidisciplinary treatment approaches make urothelial carcinoma of bladder (UCB) one of the most expensive cancers to clinically manage. Recent studies have demonstrated a role for autophagy in bladder tumorigenesis. It serves as a tumor suppressor by maintaining genomic integrity and preventing tumor proliferation during initial stages of tumor development. Nevertheless, once established, cancer cells may utilize protective autophagy to endure cellular stress and survive in the adverse environment. Its excessive stimulation supports cancer cells' resistance to therapeutic modalities.
AREAS COVERED
PubMed and Google Scholar electronic databases were searched for recently published studies. This review summarizes emerging roles of autophagy in development/progression of UCB and treatment resistance and explores novel therapeutic targets for prevention of cancer invasion, metastatic spread', and disease relapse.
EXPERT OPINION
The development of novel therapies via targeting of autophagy may augment current treatment regimens and improve clinical outcomes. Synthetic compounds or plant-based metabolites are reported to enhance cancer therapies by modulating autophagic flux. Successful autophagy-focused therapeutic intervention requires a mechanistic understanding of autophagic effects on tumor initiation and progression and the development of efficient biomarkers to monitor it in tumor tissues.
Topics: Autophagy; Carcinoma, Transitional Cell; Humans; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 34636265
DOI: 10.1080/14728222.2021.1992384 -
Urologia Internationalis 2024Squamous cell carcinoma (SCC) of the urinary bladder is the most common non-urothelial variant histology. Currently, upfront radical cystectomy is the gold standard for... (Review)
Review
BACKGROUND
Squamous cell carcinoma (SCC) of the urinary bladder is the most common non-urothelial variant histology. Currently, upfront radical cystectomy is the gold standard for non-metastatic SCC of the bladder. However, several studies have shown that SCC of the bladder is associated with higher aggressiveness and worse survival outcomes, such as progression-free and cancer-specific survival, relative to the urothelial histological subtype. Moreover, metastatic SCC seems to poorly respond to systemic treatments and/or radiotherapy.
SUMMARY
This review summarizes the current knowledge and medical evidence regarding local and systematic treatment of mSCC of the bladder, including a case series of four initially locally advanced and later metastatic SCC patients of our tertiary care hospital.
KEY MESSAGES
Despite being the second most common variant histology of bladder cancer, current therapies for SCC do not provide satisfactory therapeutic responses.
Topics: Humans; Urinary Bladder; Retrospective Studies; Urinary Bladder Neoplasms; Cystectomy; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell
PubMed: 38128507
DOI: 10.1159/000534858 -
JNMA; Journal of the Nepal Medical... Oct 2021Herniation of bladder mucosa through the bladder wall muscle layer is known as bladder diverticulum. The incidence of bladder diverticulum is 1.7. About 0.8 to 10% of...
Herniation of bladder mucosa through the bladder wall muscle layer is known as bladder diverticulum. The incidence of bladder diverticulum is 1.7. About 0.8 to 10% of the urinary bladder diverticulum develops carcinoma. Transitional cell carcinoma is the most common. Painless hematuria is the most common clinical presentation. Different imaging modalities along with cystoscopy are the key to accurate diagnosis and staging. High grade multifocal urothelial carcinoma in the bladder diverticulum is better managed by radical cystectomy and standard pelvic lymph node dissection with an ileal conduit. Here we report a case of a 66-year old gentleman of high grade multifocal urothelial carcinoma in bladder diverticulum managed with radical cystectomy and standard pelvic lymph node dissection with an ileal conduit. Such cases have been addressed adequately in the literature, but we did not find such cases from our country.
Topics: Aged; Carcinoma, Transitional Cell; Cystectomy; Humans; Lymph Node Excision; Male; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35199706
DOI: 10.31729/jnma.6228 -
European Radiology 1996Since the introduction, pelvic MRI has been considered the best non-invasive technique for primary staging of urinary bladder cancer. Before using MRI an understanding... (Comparative Study)
Comparative Study Review
Since the introduction, pelvic MRI has been considered the best non-invasive technique for primary staging of urinary bladder cancer. Before using MRI an understanding of normal and pathological MR images of the urinary bladder is essential. This review therefore describes the MR anatomy of the urinary bladder as well as the appearances of carcinoma. MRI plays an important clinical role in staging the primary tumour. In superficial tumours, clinical staging, which includes transurethral biopsy, is the best technique. For invasive tumours, MRI is superior to other techniques such as CT scanning, transvesical ultrasonography and clinical staging. A limitation of both MRI and CT scanning is their inability to recognize minimal tumour growth in the muscle layer of the bladder wall, or to differentiate between post-transurethral resection oedema and tumour. Therefore, in all patients with urinary bladder cancer staging should preferably start with MRI followed by clinical staging. Unfortunately, however, because of the high cost of this strategy, MRI has to be reserved for staging deeply invasive and superficial poorly differentiated tumours.
Topics: Biopsy; Carcinoma; Costs and Cost Analysis; Edema; Humans; Magnetic Resonance Imaging; Muscle, Smooth; Neoplasm Invasiveness; Neoplasm Staging; Postoperative Complications; Tomography, X-Ray Computed; Ultrasonography; Urinary Bladder; Urinary Bladder Diseases; Urinary Bladder Neoplasms
PubMed: 8797968
DOI: 10.1007/BF00181125 -
Asian Journal of Surgery Dec 2023
Review
Topics: Humans; Urinary Bladder; Carcinoma, Neuroendocrine; Urinary Bladder Neoplasms; Pelvis
PubMed: 37723032
DOI: 10.1016/j.asjsur.2023.09.041