Increased EpCAM expression in malignant insulinoma: potential clinical implications.
OBJECTIVE
EpCAM (CD326) is overexpressed in progenitor cells of endocrine pancreatic islands of Langerhans during fetal development and was suggested to act as a morphoregulatory molecule in pancreatic island ontogeny. We tested whether EpCAM overexpression is reactivated in insulinomas, endocrine tumors arising in the pancreas.


METHODS
We used monoclonal anti-EpCAM antibody Ber-Ep4 for immunohistochemistry on formalin-fixed and paraffin-embedded tumor material. We analyzed 53 insulinomas: 40 benign (disease stage<IIa) and 13 malignant tumors (disease stage IIIb/IV). Disease stage disposition followed new TNM classification of the European Neuroendocrine Tumor Society (ENETS) for foregut neuroendocrine tumors (2006). Additionally, ten insulinoma metastases were analyzed. Clinical follow-up was available for overall survival analysis from 49 patients. The EpCAM expression of the islands of Langerhans was classified as 2+ in healthy pancreatic tissue.


RESULTS
In 38% of the benign insulinomas (disease stage<IIa), we found strong (3+) EpCAM expression. In contrast, malignant insulinomas (disease stage IIIb/IV) and their metastases exhibited a strong (3+) EpCAM expression with 78 and 80% respectively, significantly more frequent (P<0.01). The malignant tissue was characterized by a significantly lower number of unstained cells and significantly higher number of 3+ stained cells. Quantitative PCR for EpCAM mRNA validated strong EpCAM expression in malignant insulinoma. Kaplan-Meier curves indicated survival disadvantage for EpCAM 3+ insulinomas, but this was not statistically significant (log-rank test).


CONCLUSIONS
This first EpCAM expression study in benign/malignant insulinomas indicates that strong EpCAM expression could help to identify patients at risk for malignant disease and might be used as a therapeutic target for antibody-based therapies in patients with metastatic insulinoma.
Raffel
Andreas
A
Department of General, Institute of Pathology, University Hospital of the Heinrich-Heine University Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany. raffel@med.uni-duesseldorf.de
Eisenberger
Claus F
CF
Cupisti
Kenko
K
Schott
Matthias
M
Baldus
Stephan E
SE
Hoffmann
Imke
I
Aydin
Feride
F
Knoefel
Wolfram T
WT
Stoecklein
Nikolas H
NH
D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics / Q000401:mortality; D007150:Immunohistochemistry; D007340:Insulinoma / Q000235:genetics* / Q000401:mortality* / Q000556:secondary; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D012333:RNA, Messenger