Gastric and intestinal phenotypic correlation between exocrine and endocrine components in human stomach tumors.
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".
Takenaka
Y
Y
Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Tsukamoto
T
T
Mizoshita
T
T
Ogasawara
N
N
Hirano
N
N
Otsuka
T
T
Ban
H
H
Nakamura
T
T
Yamamura
Y
Y
Kaminishi
M
M
Tatematsu
M
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D053379:Chromogranin A / Q000378:metabolism; D004702:Endocrine Glands / Q000378:metabolism / Q000473:pathology; D005088:Exocrine Glands / Q000378:metabolism / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010641:Phenotype; D013274:Stomach Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; D053379:Chromogranin A; D009363:Neoplasm Proteins