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

在过去两年的时间里，我们分析了大约400例日本人的胃肠道内分泌细胞瘤(GECT)和6个内分泌细胞癌细胞系。方法：1.将GECT分为类癌(CD)、低度恶性和内分泌细胞癌(ECC)、高度恶性两大类，并建立了组织学鉴别诊断和新的发病部位分类。组织发生：怀疑CD主要来源于未成熟的内分泌细胞。ECC可能来源于黏膜管状腺癌/腺瘤中的肿瘤内分泌细胞、全潜能干细胞、CD或未成熟的内分泌细胞。第一条路径被怀疑是最频繁的，其次是第二条。CD和ECC中P53蛋白过度表达的差异证实了它们在组织发生途径上的差异。进展和转移：GECT的细胞增殖活性被证实与肿瘤的进展和转移密切相关。对于评估肿瘤复发和转移的临床激素分析，GECT应细分为三组：Aggentaffin(产生5-羟色胺)CD、Agyrophi1(肽产生)CD和ECC(频繁产生5-羟色胺)。细胞系：由人食道、胃和直肠ECC建立的四个细胞系--分泌保存完好的激素(5-羟色胺、YY肽、降钙素)。用长春新碱和丝裂霉素作用于一株食道细胞。

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.