title: Epithelial cell adhesion molecule (EpCAM) is overexpressed in breast cancer metastases.
abstract: EpCAM (CD326) has diverse roles in cell adhesion and proliferation, and is known to be overexpressed in primary breast carcinomas (PBCs). While clinical and preclinical data suggest a role for EpCAM in metastases, the only prior study of EpCAM expression in breast cancer metastases suggested that EpCAM expression is decreased after first-line chemotherapy. This study evaluates EpCAM expression in metastatic breast carcinoma (MBC) versus matched PBC . Rapid autopsies were performed on 17 patients with widely metastatic breast cancer. Single patient tissue microarrays (TMAs) were constructed from archived PBC and post-mortem MBCs. In total, 169 spots from 17 PBCs and 895 spots from 195 MBCs were labeled for EpCAM by immunohistochemistry (IHC). Expression was scored as intensity (1-3) multiplied by percent membrane labeling (0-100%) and was subclassified as low (0-100), moderate (101-200), or high (201-300) labeling. PBCs exhibited exclusively low-moderate EpCAM labeling. EpCAM labeling was present in all metastases and was significantly increased in MBCs of 14 of 17 patients (P value range <0.05 to <0.0001, t test). In the remaining three patients, EpCAM labeling was nonsignificantly increased in 1 and unchanged in 2. High EpCAM labeling was verified using a different antibody for IHC, as well as in a separate series of surgically resected metastases compared to unmatched surgically resected primary breast cancers. In conclusion, EpCAM is highly expressed in MBCs compared to matched PBCs, verifying that it is a promising therapeutic target.
authors.affiliation: Department of Pathology, Johns Hopkins Hospital, Weinberg 2242, 401 North Broadway, Baltimore, MD 21231, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Cimino
authors.forename: Marc
authors.initials: M
authors.lastname: Halushka
authors.forename: Peter
authors.initials: P
authors.lastname: Illei
authors.forename: Xinyan
authors.initials: X
authors.lastname: Wu
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics; D001344:Autopsy; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D012333:RNA, Messenger