Abstract
BackgroundUpper urinary tract urothelial carcinoma (UTUC) accounts for only about 5–10% of all urothelial cancers and is characterized by an aggressive and frequently rapidly fatal behavior. However, detailed knowledge of its molecular profile is still lacking.Materials and methodsWe identified, by chart analysis, patients who underwent radical nephroureterectomy or diagnostic biopsy for UTUC between January 2015 and August 2020 at the Santa Maria Hospital of Terni, in Italy. Eligible patients were required to have also adequate clinical informations and follow-up details. The primary objective of the study was to evaluate DNA mismatch repair (MMR) proteins and Nectin-4 immunohistochemical expression in UTUC, looking also for an eventual correlation between these molecular features. The secondary objective was to investigate genomic instability in the case of a MMR protein loss. Expression of proteins was assessed by using immunohistochemistry and microsatellite instability (MSI) performed by next generation sequencing. Nectin-4 expression was reported using an intensity scoring system (score, 0–3+), instead the expression of DNA MMR proteins was indicated as present (no loss) or not present (loss).ResultsThirty four cases have been evaluated and 27 considered eligible for the study with their tumor samples analyzed. Nectin-4 was found to be expressed in 44% of cases and 18.5% of patients showed defective-MMR phenotype. We found a significant correlation between Nectin-4 expression and MSH2/MSH6 protein loss. Out of 7 patients with DNA MMR proteins loss or equivocal phenotype, 3 showed MSI.ConclusionsOur pilot study suggest a possible relationship between Nectin-4 and DNA MMR protein expression in UTUC and a clinically significant correlation between defective MMR phenotype and genomic instability. Because of the possible implications of these data for innovative treatment approaches, the need for further studies in this area is warranted.
Highlights
Upper urinary tract urothelial carcinoma (UTUC) accounts for only about 5–10% of all urothelial cancers and is characterized by an aggressive and frequently rapidly fatal behavior
Nectin-4 was found to be expressed in 44% of cases and 18.5% of patients showed defective-mismatch repair (MMR) phenotype
We found a significant correlation between Nectin-4 expression and MSH2/MSH6 protein loss
Summary
Upper urinary tract urothelial carcinoma (UTUC) accounts for only about 5–10% of all urothelial cancers and is characterized by an aggressive and frequently rapidly fatal behavior. Upper urinary tract urothelial carcinoma (UTUC) is a rare and heterogeneous disease, representing about 5–10% of all urothelial tumors with limited evidence in Calandrella et al BMC Cancer (2022) 22:168 literature but some emerging biologic details [1, 2]. Similar histological characteristics have been found between UTUC and lower tract carcinoma (LTUC, mainly bladder cancer), increasing evidence suggest UTUC as a distinct biologic disease with specific genetic and epigenetic features [5]. While MSI is rare in bladder cancer (3% of cases), a defective DNA MMR system has been documented in more than 15% of sporadic UTUC cases, to reiterate their different genetic profiles [7]
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