896 Defining molecular subtypes of urothelial carcinoma using tissue microarrays

2012 ◽  
Vol 11 (1) ◽  
pp. e896-e896a
Author(s):  
G. Sjödahl ◽  
K. Lövgren ◽  
M. Fernö ◽  
M. Höglund
Keyword(s):  
Urothelial Carcinoma ◽  
Molecular Subtypes ◽  
Tissue Microarrays

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.

Association of current molecular subtypes in urothelial carcinoma with patterns of muscularis propria invasion

2021 ◽  
Author(s):  
Koorosh Haghayeghi ◽  
Shaolei Lu ◽  
Andres Matoso ◽  
Stephen F. Schiff ◽  
Catrina Mueller-Leonhard ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Molecular Subtypes ◽  
Muscularis Propria

PDL1 status in muscle-invasive urothelial carcinoma in the context of neoadjuvant cisplatin-based chemotherapy.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 300-300 ◽  
Author(s):  
Jen-Jane Liu ◽  
Alexander S Baras ◽  
Nilay M Gandhi ◽  
Gunes Guner ◽  
Enrico Munari ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Therapeutic Option ◽  
Tissue Microarrays ◽  
Pathologic Response ◽  
Strong Positive Correlation ◽  
Cancer Specific Survival ◽  
Study Results ◽  
Trial Testing ◽  
Open Radical Cystectomy ◽  
Muscle Invasive

300 Background: Although complete and partial response rates to cisplatin-based neoadjuvant chemotherapy (cNAC) are 40-50% in patients with muscle-invasive urothelial carcinoma (MIUC), post-cystectomy cancer specific survival (CSS) for patients who fail to respond to cNAC is poor (5-y CSS = 27%). Therefore, up to half of MIUC could be amenable to alternative systemic therapies. Anti-programmed death ligand (PDL1) has shown promising results in tumors with proven PDL1 expression, including advanced stage MIUC. We evaluated PDL1 expression in MIUC in a cohort categorized by pathologic response to cNAC to test the hypothesis that anti-PDL1 therapy is a rational therapeutic option for patients non-responsive to cNAC. Methods: We studied 150 patients who received cNAC followed by open radical cystectomy (RC) from 2000-2013. Pathologic response (<pT1 N0 at RC) and CSS were compared to patients who had RC without cNAC. Tissue microarrays of MIUC specimens representing patients with and without response to cNAC were stained with PD-L1 (Cell-Signaling, E1L3N, 1:100) and FOXP3 (eBioscience, 236A/E7, 1:250). The degree of tumoral PDL1 and tumoral lymphocyte FOXP3 staining was manually scored. Tumors with 5% and >15/hpf staining were considered positive for PDL1 and FOXP3, respectively. Percentage of non-responders to cNAC staining positive for PDL1 was the primary outcome of our study. Results: The rate of PDL1 positivity in MIUC cNAC non-responders was 47% which was similar to the 43% rate in responders. There was a strong positive correlation of tumoral PDL1 staining with tumoral lymphocytes FOXP3 staining, Goodman-Kruskal gamma=0.71 (p<0.0001), which was independent of cNAC responder status (Table). Conclusions: Patients with MIUC that are non-responders to cNAC have poor long term CSS. Our results demonstrate that cNAC non-responders exhibit frequent PDL1 tumoral staining, suggesting that neoadjuvant or adjuvant anti-PDL1 therapy represents an attractive therapy worthy of prospective clinical trial testing in MIUC patients whose tumors do not respond to or in patients who cannot tolerate cisplatin based chemotherapy. [Table: see text]

PD18-11 DISTINCT MOLECULAR SUBTYPES AND A HIGH DIAGNOSTIC URINARY BIOMARKER OF UPPER URINARY TRACT UROTHELIAL CARCINOMA

2020 ◽  
Vol 203 ◽  
pp. e380
Author(s):  
Yoichi Fujii* ◽  
Yusuke Sato ◽  
Hiromichi Suzuki ◽  
Tetsuichi Yoshizato ◽  
Kenichi Yoshida ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urothelial Carcinoma ◽  
Molecular Subtypes ◽  
Upper Urinary Tract ◽  
Urinary Biomarker ◽  
Urinary Tract Urothelial Carcinoma

HER2 Status in Molecular Subtypes of Urothelial Carcinoma of the Renal Pelvis and Ureter

2020 ◽  
Vol 18 (4) ◽  
pp. e443-e449
Author(s):  
Takashi Yorozu ◽  
Shun Sato ◽  
Takahiro Kimura ◽  
Kosuke Iwatani ◽  
Hajime Onuma ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Renal Pelvis ◽  
Molecular Subtypes ◽  
Her2 Status

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.

Prognostic value of PD-1 and PD-L1 expression in patients with high-grade urothelial carcinoma of the upper urinary tract.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 358-358
Author(s):  
Laura-Maria Krabbe ◽  
Barbara Heitplatz ◽  
Ryan C Hutchinson ◽  
Solomon L Woldu ◽  
Sina Preuss ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Microarrays ◽  
Tumor Stage ◽  
Survival Outcomes ◽  
High Grade ◽  
Cancer Specific Survival ◽  
Infiltrating Lymphocytes

358 Background: To investigate the prognostic value of PD-1 and PD-L1 expression in patients with high-grade upper tract urothelial carcinoma (UTUC). Methods: Tissue microarrays were created using 448 patients from the International UTUC collaboration who underwent extirpative surgery for high-grade UTUC and stained for PD-1 (antibody (AB): NAT105, diluted 1:250 from Ventana) and PD-L1 (AB: E1L3N prediluted from Cell Signaling). PD-1 and PD-L1 expression was assessed in a semi-quantitative fashion and any percentage of staining of the tumor cells (PD-L1) and tumor-infiltrating lymphocytes (PD-1) was considered positive. Univariate (UVA) and multivariate analyses (MVA) were performed to assess independent prognosticators of oncological outcomes. No funding was received. Results: Median age of the cohort was 69.2 years and 56.5% of patients were male. PD-L1 and PD-1 were positive in 24.1% and 37.5% of patients. PD-L1 positivity was associated with favorable pathological stage, where as PD-1 positivity was significantly associated with pelvicalyceal location, lymph node metastases, non-organ confined disease, presence of lymphovascular invasion, sessile architecture, necrosis, concomitant CIS, and history of non-muscle invasive bladder cancer. PD-L1 positivity was not significantly associated with survival outcomes. In Cox regression UVA, PD-1 positivity was associated with worse recurrence-free survival (RFS) (HR 1.5 (95%CI 1.08-2.14, p=0.016)), cancer-specific survival (CSS) (HR 1.5 (95%CI 1.07-2.19, p=0.021)), and overall survival (OS) (HR 1.5 (95%CI 1.10-1.97, p=0.009)). However in MVA, PD-1 positivity was not found to be an independent predictor of RFS, CSS or OS. Conclusions: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and was a significant prognosticator for RFS, CSS and OS on UVA in patients treated with extirpative surgery for high-grade UTUC in a large, multi-institutional cohort. In MVA, the independent prognostic value of PD-1 was not confirmed. PD-L1 positivity was associated with lower tumor stage, but not with other pathological characteristics or survival outcomes.

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