RT Journal Article
SR Electronic
T1 Expression of EpCAM<sup>MF</sup> and EpCAM<sup>MT</sup> variants in human carcinomas
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 408
OP 414
DO 10.1136/jclinpath-2013-201932
VO 67
IS 5
A1 Fong, Dominic
A1 Seeber, Andreas
A1 Terracciano, Luigi
A1 Kasal, Armin
A1 Mazzoleni, Guido
A1 Lehne, Florian
A1 Gastl, Guenther
A1 Spizzo, Gilbert
YR 2014
UL http://jcp.bmj.com/content/67/5/408.abstract
AB Aims Regulated intramembrane proteolysis has been shown to be an important mechanism for oncogenic activation of epithelial cell adhesion molecule (EpCAM) through nuclear translocation of the intracellular domain EpICD. Recent studies have identified new membrane-bound EpCAM variants. To evaluate the prevalence of two membranous EpCAM variants in human tumours, we performed a large-scale expression analysis using specific antibodies against the extracellular domain EpEX (MOC-31 clone) and the intracellular domain EpICD (9-2 clone) of the EpCAM antigen by immunohistochemistry. Material and methods Two multi-tissue microarrays (TMA) series containing 1564 tissue samples each of 53 different histological tumour types were stained and compared. One TMA was stained for EpEX and one for EpICD. Membranous full-length EpCAM (EpCAMMF) expression in tissues was defined by the expression of EpEX and EpICD, while the truncated variant of EpCAM (EpCAMMT) was characterised by a significant loss of membranous EpICD expression compared with EpEX expression. Results We defined tumours with high EpCAMMT expression (ie, cancers of the endometrium and bladder), tumours with intermediate (ie, gastric, pancreatic, colorectal and oesophageal cancer) and tumours with low rates of expression of the EpCAMMT variant (ie, lung, ovarian, gallbladder, breast and prostate cancer). Conclusions Our results indicate that loss of membranous EpICD expression is a common event in human epithelial carcinomas, arguing for the expression of different degrees of EpCAMMF and EpCAMMT variants across the most important tumour entities. Future studies evaluating the prognostic and predictive role of these variants in human malignancies, especially in patients treated with EpCAM-specific antibodies, are clearly warranted.