Signet Ring Cells in Gastric Carcinomas Are Derived from Neuroendocrine Cells

Karin Bakkelund ^1*, Reidar Fossmark ¹, Ivar Nordrum ¹ and Helge Waldum ¹

¹ Departments of Cancer Research and Molecular Medicine (KB,RF,HW) and Laboratory Medicine, Children’s and Women’s Health (IN), Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway, and Departments of Medicine (RF,HW) and Pathology and Medical Genetics (IN), St. Olavs Hospital, Trondheim, Norway

^* To whom correspondence should be addressed. E-mail: karin.bakkelund{at}ntnu.

Submitted on August 4, 2005
Accepted on 19 November 2005

	Abstract

Adenocarcinomas are malignant tumors with glandular growth and/or supposed intracellular mucin as identified by periodic acid-Schiff positivity. Gastric signet ring cell carcinomas belong to diffuse type after Laurén. A proportion of diffuse type adenocarcinomas have previously been suggested to be of neuroendocrine origin. In the present study we wanted to examine gastric signet ring cell carcinomas for neuroendocrine differentiation. Eight of eleven gastric signet ring cell carcinomas contained areas with PAS positive signet ring cells that also were immunoreactive for one or several of the neuroendocrine markers synaptophysin, chromogranin A and histidine decarboxylase, the latter an ECL cell marker. Whereas the PAS positivity was located in the central cytoplasm, the neuroendocrine immunoreactivity was often located as a rim surrounding an otherwise nonimmunoreactive cytoplasm, presumed to represent the area with PAS positive material. These findings indicate that signet ring cell carcinomas could be of neuroendocrine origin. We propose that signet ring cell carcinomas develop by gradual dedifferentiation from ECL cells via signet ring cells with neuroendocrine immunoreactivity toward signet ring cells where the cytoplasma mainly consists of PAS positive material. This finding could have implications for the classification and understanding of gastric carcinogenesis.

Key Words: signet ring cells, neuroendocrine differentiation, CgA, synaptophysin, HDC, 5-hydroxytryptamine, somatostatin

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