Phenotypic shift in human differentiated gastric cancers from gastric to intestinal epithelial cell type during disease progression |
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Authors: | Akemi Yoshikawa Ken-ichi Inada Takasuke Yamachika Nobuyuki Shimizu Michio Kaminishi Masae Tatematsu |
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Institution: | (1) Laboratory of Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan, JP;(2) Department of Gastrointestinal Surgery, Postgraduate School of Medicine, The University of Tokyo, Tokyo, Japan, JP |
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Abstract: | Background. The phenotypic expression of tumor cells is widely thought to resemble that of the tissue of origin. In the present study,
to assess phenotypic changes that occur with disease progression, we investigated human differentiated gastric cancers at
different depths of invasion for component cancer cell types.
Methods. Using a combined mucin histochemical and immunohistochemical approach, we classified surgical specimens of 301 differentiated
gastric cancers into three types: gastric epithelial cell (G) type, intestinal epithelial cell (I) type and mixed gastric
and intestinal (GI) type, according to the phenotypic differentiation of the component cancer cells. The relation between
the phenotypic type of cancer and their depth of invasion was evaluated.
Results. The proportion of G type cancers was 41.4% in early (tumor invasion of mucosa or submucosa) cases, decreasing to 22.2% in
advanced (tumor invasion of muscularis propia or deeper) cases, whereas the proportion of I type cancers increased with progressive
disease from 23.5% to 31.1% (P < 0.01). Cancers invading the subserosa or deeper included more I type cases and fewer G type than cancers limited to the
mucosa (P < 0.01). In most cases of each phenotypic type, intestinal metaplasia was recognized in the surrounding background mucosa,
but no clear relation was shown between the phenotype of cancers and the degree of intestinal metaplasia in the background
mucosa, suggesting that intestinal metaplasia is not always a preneoplastic lesion.
Conclusions. A phenotypic shift from G to I type expression was observed with the progression of human differentiated gastric cancers.
Intestinalization may occur independently in cancerous and noncancerous gastric mucosa.
Received for publication on May 1, 1998; accepted on Oct. 22, 1998 |
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Keywords: | : human differentiated gastric cancer differentiation phenotype phenotypic change intestinalization preneoplastic lesion |
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