Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications

Favaretto, Ricardo L.; Zéqui, Stênio de Cássio; Oliveira, Renato Almeida Rosa de; Santana, Thiago Borges Marques; Costa, Walter Henriques da; Cunha, Isabela Werneck da; Guimarães, Gustavo Cardoso

doi:10.1590/s1677-5538.ibju.2017.0204

Cited by 19 publications

(26 citation statements)

References 75 publications

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“…Finally, because of the retrospective nature of the study, we were limited to the data available in the medical charts. Fu-ture studies could look at the combination of clinical markers combined with tissue-based molecular markers and inflammation scores to construct predictive and prognostic models for UTUC (32,33). Overall, the surprising predictive value of preoperative hydronephrosis regarding pathology and prognosis of UTUC might be clinically significant.…”

Section: Discussionmentioning

confidence: 99%

Preoperative hydronephrosis predicts adverse pathological features and postoperative survival in patients with high-grade upper tract urothelial carcinoma

et al. 2021

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Purpose: Epidemiological studies reported confl icting results about preoperative hydronephrosis in upper tract urothelial carcinoma (UTUC). This study aimed to investigate the association between preoperative hydronephrosis and pathologic features and oncologic outcomes in patients with UTUC treated by radical nephroureterectomy (RNU). Materials and Methods: This was a retrospective, single-center cohort study of 377 patients treated by RNU without perioperative chemotherapy between January 2001 and December 2014. Logistic regression, Cox regression, and survival analyses were performed. Results: Among the 226 patients with high-grade UTUC, 132 (58%) had preoperative hydronephrosis. Multivariable logistic regression revealed that hydronephrosis was independently associated with advanced pT stage (P=0.017) and lymph node or lymphovascular invasion (P=0.002). Median follow-up was 36 months (interquartile range: 20-48 months). The 3-and 5-year overall survival (OS) rates in patients with hydronephrosis were signifi cantly lower than in those without hydronephrosis (both P <0.001). The 3-and 5-year cancer-specifi c survival (CSS) rates in patients with hydronephrosis were signifi cantly lower than in those without hydronephrosis (both P=0.001). Hydronephrosis was independently associated with OS and CSS (P=0.001 and P=0.004, respectively). Among the 151 patients with low-grade UTUC, hydronephrosis was not associated with pathologic features and postoperative survival. Conclusions: Preoperative hydronephrosis was signifi cantly associated with adverse pathologic features and postoperative survival in patients with high-grade UTUC.

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Section: Discussionmentioning

confidence: 99%

Preoperative hydronephrosis predicts adverse pathological features and postoperative survival in patients with high-grade upper tract urothelial carcinoma

et al. 2021

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“…Interestingly, BC patients were categorized into four groups based on expression levels and subcellular localization of BLCAP; the increased expression of this protein confers a poorer prognosis for patients (64). Tissue-based molecular markers can have prognostic value not only in BC, but also in upper tract urothelial carcinoma (UTUC) (65).…”

Section: Tissue Proteomicsmentioning

confidence: 99%

Proteomic research and diagnosis in bladder cancer: state of the art review

et al. 2021

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Purpose: Proteomic biomarkers have been emerging as alternative methods to the gold standard procedures of cystoscopy and urine cytology in the diagnosis and surveillance of bladder cancer (BC). This review aims to update the state of the art of proteomics research and diagnosis in BC. Materials and Methods: We reviewed the current literature related to BC research on urinary, tissue, blood and cell line proteomics, using the Pubmed database. Findings: Two urinary protein biomarkers are FDA-approved (NMP22® and BTA® tests), only if performed along with cystoscopy for surveillance after initial diagnosis, but not in the primary diagnostic setting due to high false-positive rates in case of infections, stones and hematuria. There are a great number of non-FDA approved proteins being studied, with good preliminary results; panels of proteins seem valuable tools to be refined in ongoing trials. Blood proteins are a bigger challenge, because of the complexity of the serum protein profile and the scarcity of blood proteomic studies in BC. Previous studies with the BC tissue proteome do not correlate well with the urinary proteome, likely due to the tumor heterogeneity. Cell line proteomic research helps in the understanding of basic mechanisms that drive BC development and progression; the main difficulty is culturing low-grade tumors in vitro, which represents the majority of BC tumors in clinical practice. Conclusion: Protein biomarkers have promising value in the diagnosis, surveillance and prognostic of BC. Urine is the most appropriate body fluid for biomarker research in BC due to its easiness of sampling, stability and enrichment of shed and secreted tumor-specific proteins. Panels of biomarkers may exhibit higher sensitivity than single proteins in the diagnosis of BC at larger populations due to clinical and tumor heterogeneity. Prospective clinical trials are warranted to validate the relevance of proteomic data in the clinical management of BC.

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“…Several studies have investigated the prognostic impact of markers related to cell adhesion, cell differentiation, angiogenesis, cell proliferation (Ki-67), epithelial-mesenchymal transition, mitosis, apoptosis, and vascular invasion, and c-met protein. 21 Microsatellite instability (MSI) can help detect germline mutations and hereditary cancers. It is an independent molecular prognostic marker.…”

Section: Classification and Histologic Variantsmentioning

confidence: 99%

Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter

Bianconi¹,

Cimadamore

Faloppi

et al. 2019

Therapeutic Advances in Urology

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Upper tract urothelial carcinoma (UTUC) accounts for 5% of urothelial carcinomas (UCs), the estimated annual incidence being 1–2 cases per 100,000 inhabitants. Similarly to bladder UC, divergent differentiations and histologic variants confer an adverse risk factor in comparison with pure UTUC. Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment. Systemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic UCs. Although initial response rates are high, the median survival with combination chemotherapy is about 15 months. In first-line chemotherapy several cisplatin-based regimens have been proposed. For patients with advanced UC who progress to first-line treatment, the only product licensed in Europe is vinflunine, a third-generation, semisynthetic, vinca alkaloid. Better response rates (15–60%), with higher toxicity rates and no overall survival (OS) benefit, are generally achieved in multidrug combinations, which often include taxanes and gemcitabine. The US FDA has recently approved five agents targeting the programmed death-1 and programmed death ligand-1 pathway as a second-line therapy in patients with locally advanced or metastatic UC with disease progression during or following platinum-containing chemotherapy. Potential therapeutic targets are present in 69% of tumours analyzed. Specific molecular alterations include those involved in the RTK/Ras/PI(3)K, cell-cycle regulation and chromatin-remodeling pathways, many of them have either targeted therapies approved or under investigation. Angiogenic agents, anti-epidermal growth factor receptor therapy, phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathway inhibitors and immunotherapeutic drugs are being successfully investigated.

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Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications

Cited by 19 publications

References 75 publications

Preoperative hydronephrosis predicts adverse pathological features and postoperative survival in patients with high-grade upper tract urothelial carcinoma

Preoperative hydronephrosis predicts adverse pathological features and postoperative survival in patients with high-grade upper tract urothelial carcinoma

Proteomic research and diagnosis in bladder cancer: state of the art review

Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter

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