Endocrine cell tumors of gastrointestinal tract : molecular biological study of their histogenesis progression, and metastasis

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During the period of past two years of this project, about 400 gastrointestinal endocrine cell tumors (GECT) of Japanese and six cell lines of endocrine cell carcinoma were analyzed.1. CLASSIFICATION : GECT were divided into two main groups : carcinoid tumor (CD), low-grade malignancy and endocrine cell carcinoma (ECC), high-grade malignacy.Histological differential diagnosis and the new classification according to ocurring sites of GECT were established.2. HISTOGENESIS : CD was suspected to be mainly derived from immature endocrine cell. ECC was hypothesized to derive from neoplastic endocrine cell in mucosal tubular adenocarcinoma/adenoma, totipotential stem cell, CD,or immature endocrine cell. The first pathway was suspected to be most frequent, followed by the second. Difference in p53 protein overexpression between CD and ECC confirmed the difference in their histogenetic pathway.3. PROGRESSION AND METASTASIS : Cell proliferation activity of GECT was confirmed to correlate well with tumor progression and metastasis. For clinical hormone analysis to assess tumor recurrence and metastasis, GECT should be subdivided into three groups ; argentaffin (serotonin-producing) CD,argyrophi1 (peptide-producing) CD,and ECC (frequently serotonin-producing).4. CELL LINES : Four cell lines established from human esophageal, gastric and rectal ECC well preserved hormone (serotonin, peptide YY,calcitonin)-production. One esophageal cell line was effected by Vincristin and Mitomycin.