Molecular Pathologic Subtyping of Urothelial Bladder Carcinoma in Young Patients

2019 ◽  
Vol 27 (5) ◽  
pp. 483-491
Author(s):  
Ksenya V. Shelekhova ◽  
Kirill A. Krykow ◽  
Igor A. Mescherjakov ◽  
Nikolay P. Mitin
Keyword(s):  
Urothelial Carcinoma ◽  
Bladder Carcinoma ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Young Patients ◽  
Case Series ◽  
Aberrant Expression ◽  
Free Survival ◽  
Urothelial Bladder Carcinoma ◽  
Muscle Invasive

Urothelial cancer is a heterogeneous disease with different molecular pathways that produce distinct molecular subtypes with specific characteristics and patient survival outcomes that require different therapeutic methods. Urothelial tumors in young patients appear to have distinct genetic features compared with their counterparts in older patients. Using a Lund subtype-specific immunohistochemistry panel, we performed molecular subtype profiling of an urothelial carcinoma case series (n = 49) in patients younger than 45 years of age. We demonstrate that the urothelial carcinoma in young patients tends to be of molecular urothelial-like A subtype (80%) and is associated with favorable, recurrent-free survival ( P = .022). In the urothelial-like cluster, we identified a portion of patients (10%) with high-grade non–muscle-invasive cancers (so-called urothelial-like D type) that showed significantly higher levels of squamous differentiation and p16, E2F3, and ki67 expression in addition to aberrant expression of Ck20 and a trend toward lower recurrent-free survival ( P = .057). Segregation of the cohort according to the decade of occurrence revealed that all tumors (n = 8) of patients younger than 30 years were clearly classified as urothelial-like A subtype. Statistically more aggressive molecular subtypes, such as urothelial-like D and basal/squamous-like (6%) subtypes, were identified in patients older than 30 years of age. Genomically unstable (2%) and mesenchymal-like (2%) subtypes were classified in the 40- to 44-year age group only. These data suggest that more aggressive molecular subtypes of bladder carcinoma appear and become more frequent with age. Further investigations are needed to validate this hypothesis.

Evaluation of basal and luminal subtypes of urothelial carcinoma in African American and non-African American patients.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 305-305 ◽  
Author(s):  
Jordan Kardos ◽  
Jonathan J Melquist ◽  
David D. Chism ◽  
Woonyoung Choi ◽  
Katherine Cockerill ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
African American ◽  
Urothelial Carcinoma ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Tumor Stage ◽  
Intrinsic Subtype ◽  
Breast Cancer Patients ◽  
Muscle Invasive

305 Background: African American (AA) patients with urothelial carcinoma (UC) have been known to have a worse prognosis even when corrected for variables such as tumor stage and grade. Analysis of gene expression of several malignancies has resulted in the discovery of molecular subtypes with well-defined intrinsic biology. Recent studies in high grade (HG), muscle-invasive UC have led to the identification of two intrinsic, molecular subsets termed “luminal” and “basal” with characteristics of stages of urothelial differentiation, and that remarkably reflect the luminal and basal-like molecular subtypes of breast cancer. Patients with basal-like UC have a significantly worse overall survival. Methods: A total of 215 HG muscle-invasive UC tumors from the MDACC (n=75) and TCGA (n=140) were used to make intrinsic subtype calls using gene expression profiling (MDACC: DASL [cDNA-mediated Annealing, Selection, extension, and Ligation] and TCGA: RNA seq). Basal and luminal subtype calls were derived using previously published subtype classifiers (Damrauer et. al. PNAS, 2014 and Choi et. al. Cancer Cell, 2014). Patients were classified into AA and non-AA (white, Hispanic, or Asian) based upon self-reported race. Results: In total there were 16 and 199 tumors from AA and non-AA patients respectively. In non-AA patients, the proportion of tumors that were classified as basal and luminal were approximately equal (93 and 106 respectively), while in AA patients, there was enrichment of basal tumors (12 basal and 4 luminal) (p=0.03735, Fisher’s exact test). Conclusions: AA patients are enriched in the basal molecular subtype of UC. Similar findings have been previously documented in AA women with breast cancer. The enrichment of basal UC in AAs suggests that a biological explanation may in part underlie the poor outcomes seen in AA patients. Future studies will explore the prognostic and predictive implications of basal subtype in AA patients with UC.

scholarly journals Basal and Luminal Molecular Subtypes in Naturally-Occurring Canine Urothelial Carcinoma are Associated with Tumor Immune Signatures and Dog Breed

2021 ◽  
pp. 1-17
Author(s):  
Breann C. Sommer ◽  
Deepika Dhawan ◽  
Audrey Ruple ◽  
José A. Ramos-Vara ◽  
Noah M. Hahn ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cancer Progression ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Clinical Stage ◽  
Tumor Characteristics ◽  
Rna Seq ◽  
Advanced Clinical Stage ◽  
Naturally Occurring ◽  
Immune Signatures

BACKGROUND: Improved therapies are needed for patients with invasive urothelial carcinoma (InvUC). Tailoring treatment to molecular subtypes holds promise, but requires further study, including studies in pre-clinical animal models. Naturally-occurring canine InvUC harbors luminal and basal subtypes, mimicking those observed in humans, and could offer a relevant model for the disease in people. OBJECTIVE: To further validate the canine InvUC model, clinical and tumor characteristics associated with luminal and basal subtypes in dogs were determined, with comparison to findings from humans. METHODS: RNA sequencing (RNA-seq) analyses were performed on 56 canine InvUC tissues and bladder mucosa from four normal dogs. Data were aligned to CanFam 3.1, and differentially expressed genes identified. Data were interrogated with panels of genes defining luminal and basal subtypes, immune signatures, and other tumor features. Subject and tumor characteristics, and outcome data were obtained from medical records. RESULTS: Twenty-nine tumors were classified as luminal and 27 tumors as basal subtype. Basal tumors were strongly associated with immune infiltration (OR 52.22, 95%CI 4.68–582.38, P = 0.001) and cancer progression signatures in RNA-seq analyses, more advanced clinical stage, and earlier onset of distant metastases in exploratory analyses (P = 0.0113). Luminal tumors were strongly associated with breeds at high risk for InvUC (OR 0.06, 95%CI 0.01 –0.37, P = 0.002), non-immune infiltrative signatures, and less advanced clinical stage. CONCLUSIONS: Dogs with InvUC could provide a valuable model for testing new treatment strategies in the context of molecular subtype and immune status, and the search for germline variants impacting InvUC onset and subtype.

scholarly journals Expression of HER2/neu and Ki-67 in Urothelial Carcinoma and their Relation to Clinicopathological Data: An Egyptian Study

2021 ◽  
Author(s):  
Badawia B Ibrahim ◽  
Samira A Mahmoud ◽  
Alzahraa A Mohamed ◽  
Hala M El Hanbuli
Keyword(s):  
Urothelial Carcinoma ◽  
Bladder Carcinoma ◽  
Histological Grade ◽  
P Value ◽  
Urinary Bladder Carcinoma ◽  
Ki 67 ◽  
Urothelial Bladder Carcinoma ◽  
Cellular Marker ◽  
Urothelial Bladder ◽  
Common Malignancy

Introduction: Bladder cancer is the most common malignancy involving the urinary system and the ninth most common malignancy worldwide. Ki-67 is a nonhistone cellular marker for proliferation. HER2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma, its clinical significance remains under-investigated and poorly linked to the patients’ clinicopathological features especially with no reported Egyptian study. Aim: The aim of this work was to study the expression of HER2/neu and Ki-67 in urinary bladder carcinoma to evaluate their role in tumourigenesis and their correlation with other available clinicopathological variables associated with urothelial carcinoma. Materials and Methods: This cross-sectional study was conducted at the Department of Pathology, Faculty of Medicine, Cairo University, Egypt. Samples were paraffin blocks from 60 cases diagnosed with urothelial carcinoma underwent radical cystectomy. Ki-67 and HER2/neu immunohistochemical staining was done and of Ki-67 and HER2/neu Immunostaining was recorded. The associations between Ki-67, HER2/neu expressions and clinical and histopathological parameters of urothelial bladder carcinoma was evaluated. Results: The Ki-67 expression had significant association with tumour histological grade and lymphovascular invasion (p-value <0.05). The association of HER2/neu expression had significant association with perineural invasion (p-value <0.05). Conclusion: HER2/neu immunostaining was not associated with most of the clinicopathologic prognostic factors in urothelial bladder carcinoma.

Evaluation of β-catenin expression in muscle-invasive urothelial bladder carcinoma

2014 ◽  
Vol 27 (3) ◽  
pp. 507 ◽  
Author(s):  
MohamedSayed El Gharabawy ◽  
FatmaAhmed Elserafy ◽  
EidAbdel-Rasoul Elsherif ◽  
NohaMohamed Nor-Eldin-Elkady ◽  
TarekMohamed Abdel Elbaky ◽  
...  
Keyword(s):  
Bladder Carcinoma ◽  
Urothelial Bladder Carcinoma ◽  
Urothelial Bladder ◽  
Muscle Invasive

Is Immediate Radical Cystectomy Necessary for All Patients with Non-Muscle-Invasive Micropapillary Bladder Cancer?

2015 ◽  
Vol 96 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Benjamin L. Jackson ◽  
Aza Mohammed ◽  
Nick Mayer ◽  
John Dormer ◽  
T.R. Leyshon Griffiths
Keyword(s):  
Urothelial Carcinoma ◽  
Prognostic Indicator ◽  
Lymph Node Involvement ◽  
Morphological Marker ◽  
Free Survival ◽  
Non Invasive ◽  
Node Involvement ◽  
Resection Specimen ◽  
Muscle Invasive

Introduction: We aim to review the outcomes of micropapillary urothelial carcinoma (MPUC) of the bladder from a single institution. The hypothesis is that non-muscle-invasive (NMI) MPUC may have a heterogeneous prognosis, and detailed pathological analysis may identify patients that could be managed without immediate cystectomy. Patients and Methods: This is a retrospective analysis of patients presenting with MPUC in a primary transurethral resection specimen (n = 40). The pattern of micropapillary (MP) differentiation [surface/non-invasive (sMP) or invasive (iMP)], extent of MP differentiation and lymphovascular invasion (LVI) were correlated with overall survival (OS), recurrence-free survival and upstaging at re-resection. Results: Sixteen of 40 patients died after a median follow-up of 37 months. Tumour stage was strongly predictive of OS (p < 0.0001). LVI was associated with increased mortality (hazard ratio 12.4, 95% CI: 3.5-44.5, p = 0.0001), higher pathological stage (p = 0.001), lymph node involvement (p = 0.001) and iMP differentiation (p = 0.006). In NMI patients not undergoing cystectomy (n = 17), NMI-sMP compared with NMI-iMP differentiation was associated with an improved OS when compared with iMP (63 vs. 47 months, p = 0.05). Conclusions: MPUC is an aggressive variant of urothelial carcinoma (UC). Similar to conventional UC, LVI associated with MPUC is an adverse prognostic indicator. iMP is a morphological marker for LVI. Histopathological reports should distinguish between sMP and iMP differentiation.

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