Carcinogenic hypergastrinemia: signet-ring cell carcinoma in a patient with multiple endocrine neoplasia type 1 with Zollinger-Ellison's syndrome.
BACKGROUND
Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families.


OBJECTIVE
In this study we investigated the histopathological and molecular findings in the gastrointestinal wall of a patient with multiple endocrine neoplasia type 1 with malignant duodenal gastrinoma and multiple gastric ECL cell tumors, who additionally developed a signet-ring cell carcinoma of the stomach.


METHODS
Biopsies from the gastrointestinal tract of a patient with multiple endocrine neoplasia type 1 were immunostained for vesicular monoamine transporter-2 and E-cadherin. Nonamidated gastrin products were measured in the serum of the patient using antibodies that react with progastrin, Gly-extended, and amidated gastrins. Genetic analyses were performed to exclude germ-line mutations within the E-cadherin gene.


RESULTS
Immunohistochemical studies of gastric ECL cell tumors showed a largely diminished E-cadherin expression in comparison to gastric surface mucosa cells and a loss of E-cadherin expression in the cells of the signet-ring carcinoma. Detailed biochemical measurements revealed progastrin concentrations that were approximately 20%, and Gly-gastrin concentrations that were approximately 10% the amidated gastrin concentrations in plasma. Molecular analyses revealed no E-cadherin germ-line mutation.


CONCLUSIONS
Our immunohistochemical studies might suggest that the gastrinoma-associated excessive progastrin tissue concentrations led to diminished expression of E-cadherin within the gastric mucosa and promoted tumor development of a signet-ring cell carcinoma.
Schott
Matthias
M
Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany. schottmt@uni-duesseldorf.de
Sagert
Cornelia
C
Willenberg
Holger S
HS
Schinner
Sven
S
Ramp
Uwe
U
Varro
Andrea
A
Raffel
Andreas
A
Eisenberger
Claus
C
Zacharowski
Kai
K
Perren
Aurel
A
Scherbaum
Werner A
WA
D015820:Cadherins / Q000235:genetics; D018279:Carcinoma, Signet Ring Cell / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D005755:Gastrins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018761:Multiple Endocrine Neoplasia Type 1 / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D013274:Stomach Neoplasms / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D014463:Ultrasonography; D015043:Zollinger-Ellison Syndrome / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology
D015820:Cadherins; D005755:Gastrins