EpCAM Expression in Lymph Node Metastases of Urothelial Cell Carcinoma of the Bladder: A Pilot Study

Fels, Christa A.M. van der; Rosati, S.; Jong, Igle J. de

doi:10.3390/ijms18081802

Cited by 12 publications

(13 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EpCAM is highly and frequently expressed in the vast majority of carcinomas that have been analyzed [11,12] and its expression in metastases frequently correlates with levels in the corresponding primary tumors ( Fig. 4 and [13,14,21,55]). As such, EpCAM bears potential as a prognostic and therapeutic marker in carcinomas and during cancer progression and metastasis formation.…”

Section: Epcam As a Prognostic Marker In Cancermentioning

confidence: 98%

“…Frequent and high-level expression of EpCAM on various carcinomas (98 out of 131 tested) [11,12] and metastases [13,14], and a correlation with clinical outcome qualified it as prognostic marker and therapeutic target [15]. EpCAMspecific antibody Panorex® (edrecolomab; 17-1A) first attained market approval for treating colorectal carcinomas in 1995 [16].…”

Section: Clinical Significance In Cancermentioning

confidence: 99%

See 1 more Smart Citation

Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?

Gires

Pan

Schinke

et al. 2020

Cancer Metastasis Rev

203

140

View full text Add to dashboard Cite

EpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, EpCAM is reckoned as a multi-functional transmembrane protein involved in the regulation of cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. To fulfill these functions, EpCAM is instrumental in intra- and intercellular signaling as a full-length molecule and following regulated intramembrane proteolysis, generating functionally active extra- and intracellular fragments. Intact EpCAM and its proteolytic fragments interact with claudins, CD44, E-cadherin, epidermal growth factor receptor (EGFR), and intracellular signaling components of the WNT and Ras/Raf pathways, respectively. This plethora of functions contributes to shaping intratumor heterogeneity and partial EMT, which are major determinants of the clinical outcome of carcinoma patients. EpCAM represents a marker for the epithelial status of primary and systemic tumor cells and emerges as a measure for the metastatic capacity of CTCs. Consequentially, EpCAM has reclaimed potential as a prognostic marker and target on primary and systemic tumor cells.

show abstract

Section: Epcam As a Prognostic Marker In Cancermentioning

confidence: 98%

Section: Clinical Significance In Cancermentioning

confidence: 99%

Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?

Gires

Pan

Schinke

et al. 2020

Cancer Metastasis Rev

203

140

View full text Add to dashboard Cite

show abstract

“…The immunostaining was evaluated semi quantitatively by an experienced genitourinary pathologist (M.H. ), in a manner that was described previously [ 11 , 12 , 13 ]. The proportion score (PS) multiplied by the intensity score (IS) resulted in the total immunostaining (TIS).…”

Section: Methodsmentioning

confidence: 99%

“…Both VEGF and EGFR have been used as a radiolabeled imaging agent for molecular imaging in the previously mentioned tumors [ 9 , 10 ]. Previously we reported epithelial cell adhesion molecule (EpCAM) to be an antigen with high tumor distinctiveness for LN positive disease in urothelial cell carcinoma (UCC) of the bladder [ 11 ]. Besides imaging modalities, the above mentioned antigens have been used for the development of therapeutic purposes as well.…”

Section: Introductionmentioning

confidence: 99%

Potential Receptors for Targeted Imaging of Lymph Node Metastases in Penile Cancer

et al. 2020

View full text Add to dashboard Cite

Imaging modalities using tumor-directed monoclonal antibodies may be of value to improve the pre- and intraoperative detection and resection of lymph node (LN) metastatic disease in penile squamous cell carcinoma (PSCC). We investigated the expression of prostate-specific membrane antigen (PSMA), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) to analyze their potency for diagnostic applications. Antigen expression was determined in primary tumors and LNs with and without metastases of 22 patients with PSCC. The total immunostaining score (TIS, 0–12) was determined as the product of a proportion score (PS, 0–4) and an intensity score (IS, 0–3). EGFR and VEGF expression were high in primary tumor (median TIS 8) and LN metastases (median TIS 6 and 8, respectively). No EGFR expression was seen in LNs without metastases. However, LNs without metastases did show VEGF expression (median TIS 6). No EpCAM or PSMA expression was seen in PSCC. This study shows that VEGF and EGFR expression is moderate to high in LN metastases of PSCC. Both VEGF and EGFR warrant further clinical evaluation to determine their value as a target for pre- and intraoperative imaging modalities in the detection of LN metastases in PSCC.

show abstract

“…To address our hypothesis, we isolated benign epithelial cells from the renal pelvis, prostatic urethra, and bladder using an epithelial marker, EPCAM, and a basal urothelial marker, CD49f (23,24). We found that primary human urothelial cells can be divided into 2 populations (CD49f high and CD49f low ) ( Fig.…”

Section: Sccb and Other Bladder Cancer Phenotypes Can Be Initiated Frommentioning

confidence: 98%

A genetically defined disease model reveals that urothelial cells can initiate divergent bladder cancer phenotypes

Wang

Smith

Balanis

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Small cell carcinoma of the bladder (SCCB) is a rare and lethal phenotype of bladder cancer. The pathogenesis and molecular features are unknown. Here, we established a genetically engineered SCCB model and a cohort of patient SCCB and urothelial carcinoma samples to characterize molecular similarities and differences between bladder cancer phenotypes. We demonstrate that SCCB shares a urothelial origin with other bladder cancer phenotypes by showing that urothelial cells driven by a set of defined oncogenic factors give rise to a mixture of tumor phenotypes, including small cell carcinoma, urothelial carcinoma, and squamous cell carcinoma. Tumor-derived single-cell clones also give rise to both SCCB and urothelial carcinoma in xenografts. Despite this shared urothelial origin, clinical SCCB samples have a distinct transcriptional profile and a unique transcriptional regulatory network. Using the transcriptional profile from our cohort, we identified cell surface proteins (CSPs) associated with the SCCB phenotype. We found that the majority of SCCB samples have PD-L1 expression in both tumor cells and tumor-infiltrating lymphocytes, suggesting that immune checkpoint inhibitors could be a treatment option for SCCB. We further demonstrate that our genetically engineered tumor model is a representative tool for investigating CSPs in SCCB by showing that it shares a similar a CSP profile with clinical samples and expresses SCCB–up-regulated CSPs at both the mRNA and protein levels. Our findings reveal distinct molecular features of SCCB and provide a transcriptional dataset and a preclinical model for further investigating SCCB biology.

show abstract

EpCAM Expression in Lymph Node Metastases of Urothelial Cell Carcinoma of the Bladder: A Pilot Study

Cited by 12 publications

References 24 publications

Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?

Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?

Potential Receptors for Targeted Imaging of Lymph Node Metastases in Penile Cancer

A genetically defined disease model reveals that urothelial cells can initiate divergent bladder cancer phenotypes

Contact Info

Product

Resources

About