INTESTINE Vol.6 No.3(8)

Theme Colorectal carcinoid tumors -- New strategy of treatment
Title Genetic alterations of neuroendocrine cell tumor during its development and progression
Publish Date 2002/05
Author Hitoshi Kawamata Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine
Author Johji Imura Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine
Author akahiro Fujimori Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine
[ Summary ] We proposed a hypothetical pathway for the development of neuroendocrine cell (NEC) tumors, carcinoid and NEC carcinoma in the digestivetract. We presented a case with a composite tumor, consisting of adenocarcinoma and argyrophil NEC carcinoma. All tumor regions showed a point mutation in p53 gene at exon 7 (GGC to GTC at codon 245). The distal portion of NEC carcinoma showed an additional point mutation in p53 gene at exon 5 (GCC to GTC at codon 129). On the other hand, we investigated the expression of COX-2, and the relationship between COX-2 expression and K-ras mutation in colorectal adenomas. We found that COX-2 was expressed in some NECs in the adenomas. An increase of COX-2-positive cells in adenoma was observed in 11 out of 29 lesions, 10 of which had a K-ras gene mutation. Moreover, most of the colorectal adenocarcinomas over-expressed COX-2 and showed K-ras mutation, whereas none of the NEC tumors showed either over-expression of COX-2 or K-ras mutation.
These results indicate that adenocarcinoma and NEC carcinoma are sometimes derived from a common epithelial cells in the digestive tract, and that different genetic alterations may also be involved in the development of colorectal adenocarcinoma and NEC tumors.
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