Gastric and intestinal phenotypic correlation between exocrine and endocrine components in human stomach tumors
Y. Takenaka1,2, T. Tsukamoto1, T. Mizoshita1, N. Ogasawara1, N. Hirano1, T. Otsuka1, H. Ban1, T. Nakamura3, Y. Yamamura4, M. Kaminishi2 and M Tatematsu1
1Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan, 2Department of Gastrointestinal Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan, 3Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan and 4Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Japan. *These authors contributed equally to this work.
Offprint requests to: Tetsuya Tsukamoto, MD, Ph D, Division of Oncological Pathology, Aichi Cancer Centr Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. e-mail: firstname.lastname@example.org
Summary. We have previously suggested that an origin of a stomach cancer is from a progenitor cell specializing toward exocrine cell (Exo-cell) lineages. To clarify whether our hypothesis is correct or not, we analyzed the expression of Exo-cell and endocrine cell (End-cell) markers in a series of lesions for comparison. We evaluated chromogranin A (CgA) expression in 37 early and 73 advanced stomach cancers, in 30 stomach adenomas, in 8 carcinoid tumors, and in 4 endocrine cell carcinomas (ECCs) with assessment of gastric and/or intestinal (G/I) phenotypes in both Exo-cell and End-cell by immunohistochemistry. CgA expression was observed in 10.8% of the early and 16.4% of the advanced stomach cancers, respectively. The End-cell G/I phenotypes were in line with the Exo-cell counterparts in the CgA-positive stomach cancerous areas, and there was strong association between Cdx2 expression and the intestinal End-cell markers. All of the adenoma cases had the intestinal Exo-cell phenotypic expression, with the positive link between Exo-cell and End-cell G/I phenotypes. All stomach carcinoids had CgA expression but no expression of Exo-cell markers. In conclusion, most stomach cancers might develop from a progenitor cell specializing towards Exo-cell lineages, but some cases possessed both Exo-cell and End-cell markers with maturely differentiated phenotypes. In such cases, Exo-cell and End-cell phenotypes were found to correlate strongly, suggesting the possibility of histogenesis from “cancer stem cells”. Histol Histopathol 22, 273-284 (2007)
Key words: Stomach cancers, Endocrine cell, Phenotypes, Progenitor cell, Cancer stem cells