Evaluation of HER2 expression in urothelial carcinoma cells as a biomarker for circulating tumor cells

Abstract

BackgroundDetection of circulating tumor cells (CTC) by techniques based on epithelial cell adhesion molecule (EpCAM) is suboptimal in urothelial carcinoma (UC). As HER2 is thought to be broadly expressed in UC, we explored its utility for CTC detection.MethodsHER2 and EpCAM expression was analyzed in 18 UC cell lines (UCCs) by qRT‐PCR, western blot and fluorescence‐activated cell scanning (FACS) and compared to the strongly HER2‐expressing breast cancer cell line SKBR3 and other controls. HER2 expression in UC patient tissues was measured by qRT PCR and correlated with data on survival and risk for metastasis. UCCs with high EpCAM and variable HER2 expression were used for spike‐in experiments in the CellSearch system. Twenty‐one blood samples from 13 metastatic UC patients were analyzed for HER2‐positive CTCs with CellSearch.ResultsHER2 mRNA and protein were broadly expressed in UCC, with some heterogeneity, but at least 10‐fold lower than in the HER‐2+ SKBR3 cells. Variations were unrelated to cellular phenotype or clinicopathological characteristics. EpCAM expression was essentially restricted to UCCs with epitheloid phenotypes. Heterogeneity of EpCAM and HER2 expression was observed also in spike‐in experiments. The 7 of 21 blood samples from 6 of 13 patients were enumerated as CTC positive via EpCAM, but only one sample stained weakly positive (1+) for HER2.ConclusionsDetection rate of CTCs by EpCAM in UC is poor, even in metastatic patients. Because of its widespread expression, particularly in patients with high risk of metastasis, detection of HER2 could improve identification of UC CTCs, which is why combined detection using antibodies for EpCAM and HER2 may be beneficial.

A multimodal molecular imaging approach targeting urokinase plasminogen activator receptor for the diagnosis, resection and surveillance of urothelial cell carcinoma

“…Ideally, these tracers visualise unique characteristics of UCC which distinguishes the tumour from adjacent normal tissue. In case of uPAR and EpCAM, these membrane receptors have complementary expression patterns during the complex multistep process of switching from a sessile to an invasive cancer cell [24,25]. In addition to uPAR targeting, we show our recently introduced EpCAM-targeting tracer, which is currently being evaluated on patients with gastrointestinal cancer, could also be used for UCC (NL7363) [26].…”

Evaluation of HER2/neu and SPINK1 as an adjunct to the prognosis of urothelial dysplasia and urothelial carcinoma of the urinary bladder

“…Also, no statistically significant relation could be detected between HER2 expression and grading of UD cases. Similarly, in a study by Mohamad et al (2014) and Nini et al (2020) no statistically significant relation was reported regarding age and sex with respect to HER2 overexpression in their studied cases.…”

Enhanced Cytotoxic Activity of PEGylated Curcumin Derivatives: Synthesis, Structure–Activity Evaluation, and Biological Activity

“…Thus, the interaction of BF 2 -possessing compounds with HER2 receptors can be involved in the cytotoxic activity of these compounds [ 32 ]. Based on the literature data, both cell lines used in our studies, 5637 and SCaBER, expressed the HER2 receptor [ 39 ]. The similar IC 50 values calculated for our BF 2 complexes toward 5637 and SCaBER cells could potentially result from this interaction.…”