title: Notch 1 tumor expression is lacking in highly proliferative pancreatic neuroendocrine tumors.
abstract: To date, very little is known about the development of benign organic hyperinsulinism and its metastatic potential. Typical morphologic, biochemical, or genetic differentiations for benign or malign tumor course of insulinomas do not exist. As signaling pathways may affect pancreatic cancer development and the maintenance of the neoplastic phenotype, the purpose of this study was to examine the role of Notch1 expression in organic hyperinsulinism. We examined 32 well-differentiated pancreatic endocrine tumors (wd PET); 11 wd PET of unknown behavior (wd PET ub); and 15 wd pancreatic endocrine cancer (wd PEC) for Notch1 expression by immunohistochemistry. Demographic data, clinical data, and follow-up of all patients were analyzed. Islets of the Langerhans show the strongest Notch1 staining in nearly 90 %. Positive Notch1 staining was absent in the acinar of the pancreas. In patients with a wd PET more than every second tumor (56.3 %/n = 18/32) demonstrated a negative Notch1 staining. The other 14 patients were positive for Notch1. Tumors of unknown behavior (wd PET ub) and malignant insulinomas had no signs of Notch expression in contrast to benign insulinomas. Considering the clinical and histomorphological tumor behavior, no correlation between Notch1 expression and clinical data was found. The missing Notch expression in the malignant tumor course might be used as a potential predictive marker, but further studies are needed to investigate the underlying molecular mechanism.
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Krausch
authors.forename: Feride
authors.initials: F
authors.lastname: Kroepil
authors.forename: Nadja
authors.initials: N
authors.lastname: Lehwald
authors.forename: Anja
authors.initials: A
authors.lastname: Lachenmayer
authors.forename: Matthias
authors.initials: M
authors.lastname: Schott
authors.forename: Martin
authors.initials: M
authors.lastname: Anlauf
authors.forename: Kenko
authors.initials: K
authors.lastname: Cupisti
authors.forename: Wolfram Trudo
authors.initials: WT
authors.lastname: Knoefel
authors.forename: Andreas
authors.initials: A
authors.lastname: Raffel
mesh_terms: D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051881:Receptor, Notch1 / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1