Evaluation of Therapeutic Targets in Histological Subtypes of Bladder Cancer

Abstract

Histologically, bladder cancer is a heterogeneous group comprising urothelial carcinoma (UC), squamous cell carcinoma, adenocarcinomas (ACs), urachal carcinomas (UrCs), and small cell neuroendocrine carcinomas (SCCs). However, all bladder cancers have been treated so far uniformly, and targeted therapy options are still limited. Thus, we aimed to determine the protein expression/molecular status of commonly used cancer targets (programmed cell death 1 ligand 1 (PD-L1), mismatch repair (MMR), androgen and estrogen receptors (AR/ER), Nectin-4, tumor-associated calcium signal transducer 2 (Tacstd2, Trop-2), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and fibroblast growth factor receptor 3 (FGFR3)) to give first insights into whether patients with SCC, AC/UrCs, and squamous-differentiated carcinomas (Sq-BLCA) of the bladder could be eligible for targeted therapies. In addition, for MMR-deficient tumors, microsatellite instability was analyzed. We completed our own data with molecular data from The Cancer Genome Atlas (TCGA). We present ratios for each drug and cumulative ratios for multiple therapeutic options for each nonurothelial subtype. For example, 58.9% of SCC patients, 33.5% of AC/UrCs patients, and 79.3% of Sq-BLCA patients would be eligible for at least one of the analyzed targets. In conclusion, our findings hold promise for targeted therapeutic approaches in selected patients in the future, as various drugs could be applied according to the biomarker status.

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

“…Behzatoglu et al reported the presence of HER2 overexpression in 56% of micropapillary carcinomas (MPCs) and only 36% of conventional BCs; on the other hand, HER2 positivity rates declined to 20% in the group of BCs with squamous differentiation (SD-BC), and no expression was seen in the cases of sarcomatoid carcinoma (SCs) and BC with glandular differentiation (GD-BC) [ 67 ], in keeping with the findings by Wang et al on a cohort of upper urinary tract UCs [ 68 ]. Even lower positivity rates (3–11%) of HER2 amplification/overexpression in SD-BCs were reported in two studies [ 69 , 70 ].…”

Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value—Need for Biomarker Testing in High-Risk Patients?

“…First, we examined the expression of Nectin-4 by immunohistochemistry in SCC, ADENO, and SARCO. As described in the literature, a partly cytoplasmic, partly membranous staining for Nectin-4 was observed in tumor cells [ 15 , 16 ]. Immunoreactivity was scored using the H-score as described.…”

Glandular Lesions of the Urinary Bladder: Diagnostic and Molecular Updates

“…14,[24][25][26] However, current studies detected potentially targetable molecular alterations in PBAC in 33.5% to 67% of cases. 26,27 Therefore, molecular testing for predictive biomarkers might be helpful in advanced cases.…”