Endocrine cell tumors of gastrointestinal tract : histogenesis, growth, metastasis and racial differences

本课题在近两年的时间里，收集并分析了胃肠道内分泌细胞肿瘤。胃肠道内分泌细胞肿瘤分为类癌（CD）、低级别恶性和内分泌细胞癌（ECC）、高级别恶性两组。建立了这两种实体的组织学鉴别诊断。乳糜泻被认为主要来源于未成熟的内分泌细胞。假设ECC来源于粘膜小管腺癌中的肿瘤内分泌细胞，如坏化瘤、全潜能干细胞、CD或未成熟的内分泌细胞。第一种途径被认为是最常见的，其次是第二种。这些假设在p53和LOH.3的分子水平上得到证实。根据发生地点的不同，建立了CD和ECC的新分类。建立了p58蛋白过表达和细胞增殖活性在CD和ECC之间的差异。即使在分化良好的ECC细胞中，p53蛋白的过表达和细胞增殖活性也降低或丧失。从人食管、胃和直肠ECC中建立的四种细胞系显示，它们很好地保存了激素（促缩素、肽YY、降钙素）的产生。长春新素和丝裂霉素对食道ECC细胞株的影响。

During the period of past two years of this particular project, endocrine cell tumors of the gastrointestinal tract were collected and analyzed.1. Endocrine cell tumors of the gastrointestinal tract were divided into two groups : carcinoid tumor(CD), low-grade malignancy and endocrine cell carcinoma(ECC), high-grade malignancy. Histological differential diagnosis between these two entities was established.2. CD was thought to be mainly derived from immature endocrine cells. ECC was hypothesized to derive from neoplastic endocrine cell in mucosal tubular adenocarcinoma orade noma, totipotential stem cell, CD, or immature endocrine cell. The first pathway was suspected to be most frequent, followed by the second. These hypothesis was confirmed by molecular level on p53 and LOH.3. New classification on CD and ECC according to different ocurring sites was established.4. Difference of p58 protein overexpression and cell proliferation activity between CD and ECC were established. p53 protein overexpression and cell proliferation activity were decreased or lost even in well differentiated ECC cells.5. Four cell lines established from human esophageal, gastric and rectal ECC revealed a well preservation of hormone(srotonin, peptide YY, calcitonin)-production. Cell line from esophageal ECC was effected by Vincristin and Mitomycin.