HER2 Expression in Bladder Cancer: A Focused View on Its Diagnostic, Prognostic, and Predictive Role

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3720 - 3720

Published: Feb. 13, 2023

Bladder cancer (BC) is a heterogeneous disease from molecular, morphological, and clinical standpoint. HER2 known oncogene involved in bladder carcinogenesis. Assessing overexpression as result of its molecular changes routine pathology practice using immunohistochemistry might be useful adjunct several scenarios, namely (1) to correctly identify flat urothelial lesions inverted the diagnostic setting; (2) provide prognostic hints both non-muscle invasive (NMI) muscle (MI) tumors, thus supplementing risk stratification tools, especially when evaluating higher-risk tumors such those with variant morphology; (3) improve antibody panels surrogate marker BC subtyping. Furthermore, potential therapeutic target has been only partly explored so far, light ongoing development novel therapies.

Language: Английский

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The effect of neoadjuvant chemotherapy on survival outcomes in patients with variant histologies who underwent radical cystectomy with precystectomy diagnostic accuracy: A multicenter study of the Turkish Urooncology Association

International Journal of Urology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

To evaluate the role of neoadjuvant chemotherapy in final treatment plan and its impact on survival bladder cancer patients who were diagnosed with variant histology radical cystectomy specimen whose diagnostic accuracy was achieved previous transurethral resection specimen. In this retrospective multicenter study, data from 221 across 9 centers analyzed between January 2012 2022. The primary endpoint overall, cancer-specific, recurrence-free, metastasis-free rates among without chemotherapy, secondary to identify independent predictors survival. Kaplan-Meier method used estimate overall survival, cancer-specific recurrence-free multivariate analyses performed using Cox-regression model. estimates demonstrated no significant difference two groups. Cox multifactorial analysis revealed that age (HR 1.030, 95% CI 1.003-1.057, p = 0.027), presence pT4 tumor stage 3.861, 1.303-11.494, 0.015), pN+ 2.288, 1.475-3.550, < 0.001) at histopathology survival; 8.245, 1.873-36.292, 0.005 HR 1.792, 1.049-3.061, 0.033) 9.957, 1.286-77.073, 0.028 2.949, 1.674-5.197, 0.001); 1.047, 1.006-1.090, 0.025) 4.150, 1.917-8.981, Neoadjuvant does not provide any advantage histology; therefore, considering disadvantages, such as delaying cystectomy, which can lead inadvertent disease progression chemotherapy-related toxicities, cautious should be exercised when administering chemotherapy.

Language: Английский

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Non-muscle-invasive bladder cancer: An overview of potential new treatment options

Urologic Oncology Seminars and Original Investigations, Journal Year: 2021, Volume and Issue: 39(10), P. 642 - 663

Published: June 22, 2021

This review article summarizes the current clinical practice guidelines around disease definitions and risk stratifications, treatment of non-muscle-invasive bladder cancer (NMIBC). Recently completed ongoing trials novel investigational therapies in Bacillus Calmette-Guérin (BCG)-naïve, BCG-recurrent, BCG-unresponsive patient populations are also described, e.g., those involving immune checkpoint inhibitors, targeted therapies, other chemotherapy regimens, vaccines, viral- or bacterial-based treatments. Finally, a brief overview enhanced cystoscopy drug delivery systems for diagnosis NMIBC is provided.A global shortage access to BCG affecting management BCG-naïve BCG-recurrent/unresponsive NMIBC; hence, there an urgent need assist patients urologists enhance this disease.Searches ClinicalTrials.gov, PubMed, Google Scholar were conducted. Published guidance conference proceedings from major congresses reviewed.Treatment strategies generally consistent across guidelines. Several have demonstrated promising antitumor activity trials, including high-risk disease. The detection, diagnosis, surveillance, been improved through detection.

Language: Английский

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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 3166 - 3166

Published: Nov. 14, 2021

Immunotherapy targeting the PD-1-PD-L1 axis yielded good results in treating different immunologically ''hot'' tumors. A phase II study revealed therapeutic activity of pembrolizumab selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes immunohistochemical expression PD-L1 human PC samples and highlights pre-analytical interpretation variables. Interestingly, 29% acinar PCs, 7% ductal 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohistochemistry. Different scoring methods or cut-off criteria applied variable specimen-types, evaluating tumors showing clinic-pathologic features. The positivity rate antibody clones tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding single case tested for RM-320. most clone was E1L3N, followed by 22C3 (most used eligibility), SP263, SP142, 28-8, gave rates 35%, 11-41% (depending systems), 6%, 3%, 15%, respectively. Other <200 cases. usually higher than benign tissues. It non-tissue microarray specimens (41-50% vs. 15%), as frequently showed heterogenous focal PD-L1-staining. expressed immune stromal 12% 69% cases, Tumor heterogeneity, inter-institutional preanalytics, inter-observer variability may account result biases.

Language: Английский

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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12330 - 12330

Published: Nov. 15, 2021

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in cells. TME influences the survival/progression of prostate cancer (PC), enabling cell immune-evasion also through activation PD-1/PD-L1 axis. We have performed a systematic literature review according to PRISMA guidelines, investigate how pathway is influenced by ISPs. Tumor immune-escape mechanisms include suppression/exhaustion infiltrating cytotoxic T lymphocytes, inhibition suppressive NK increase immune-suppressive cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, other soluble molecules secreted components (and sometimes increased patients' serum), as well hypoxia, regulation PD-L1. Experimental studies using human mouse PC lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that ERK/MEK, Akt-mTOR, NF-kB, WNT JAK/STAT were involved PD-L1 upregulation PC. Blocking immunotherapy drugs can prevent immune-escape, increasing anti-tumor activity

Language: Английский

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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review (Part 6): Correlation of PD-L1 Expression with the Status of Mismatch Repair System, BRCA, PTEN, and Other Genes

Biomedicines, Journal Year: 2022, Volume and Issue: 10(2), P. 236 - 236

Published: Jan. 22, 2022

Pembrolizumab (anti-PD-1) is allowed in selected metastatic castration-resistant prostate cancer (PC) patients showing microsatellite instability/mismatch repair system deficiency (MSI-H/dMMR).

Language: Английский

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Impact of variant histology on upstaging and survival in patients with nonmuscle invasive bladder cancer undergoing radical cystectomy

Urologic Oncology Seminars and Original Investigations, Journal Year: 2024, Volume and Issue: 42(3), P. 69.e11 - 69.e16

Published: Jan. 23, 2024

Language: Английский

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Diagnostic workout of glandular malignant lesions of the bladder according to the 5th WHO classification

Critical Reviews in Clinical Laboratory Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: March 9, 2025

Glandular lesions involving the bladder are less common than conventional urothelial carcinoma, and they often diagnostically challenging diseases, carrying different clinical outcomes. As a group, encompass both primary secondary neoplasms, with sometimes overlapping morphological features. In this scenario, proper information is important, in that involvement of may occur by direct extension or lymphatic/hematogenous spread from carcinomas at other sites, comprising prostate, colon, cervix, breast, lung. According to 5th edition WHO Classification urological tumors, glandular morphology major hallmark following entities: carcinoma differentiation, adenocarcinoma, NOS, urachal tumors Mullerian type. The distinction among these entities, between heavily relies on their biological immunophenotypical This article will review neoplasms bladder, highlighting main markers. Furthermore, molecular data associated pathogenesis, prognosis, treatment be described. aim study provide practical comprehensive up-to-date overview complex topic.

Language: Английский

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Prognostic impact of variant histology in bladder cancer: Would early and aggressive treatment shift the paradigm?

Urologic Oncology Seminars and Original Investigations, Journal Year: 2024, Volume and Issue: 42(5), P. 161.e1 - 161.e8

Published: Jan. 23, 2024

Language: Английский

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Cell-targeting Nanomedicine for Bladder Cancer: A Cellular Bioengineering Approach for Precise Drug Delivery

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: unknown, P. 106220 - 106220

Published: Sept. 1, 2024

Language: Английский

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