Schott Matthias, Sagert Cornelia, Willenberg Holger S, Schinner Sven, Ramp Uwe, Varro Andrea, Raffel Andreas, Eisenberger Claus, Zacharowski Kai, Perren Aurel, Scherbaum Werner A
Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany.
J Clin Endocrinol Metab. 2007 Sep;92(9):3378-82. doi: 10.1210/jc.2007-0283. Epub 2007 Jul 3.
Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families.
In this study we investigated the histopathological and molecular findings in the gastrointestinal wall of a patient with multiple endocrine neoplasia type 1 with malignant duodenal gastrinoma and multiple gastric ECL cell tumors, who additionally developed a signet-ring cell carcinoma of the stomach.
Biopsies from the gastrointestinal tract of a patient with multiple endocrine neoplasia type 1 were immunostained for vesicular monoamine transporter-2 and E-cadherin. Nonamidated gastrin products were measured in the serum of the patient using antibodies that react with progastrin, Gly-extended, and amidated gastrins. Genetic analyses were performed to exclude germ-line mutations within the E-cadherin gene.
Immunohistochemical studies of gastric ECL cell tumors showed a largely diminished E-cadherin expression in comparison to gastric surface mucosa cells and a loss of E-cadherin expression in the cells of the signet-ring carcinoma. Detailed biochemical measurements revealed progastrin concentrations that were approximately 20%, and Gly-gastrin concentrations that were approximately 10% the amidated gastrin concentrations in plasma. Molecular analyses revealed no E-cadherin germ-line mutation.
Our immunohistochemical studies might suggest that the gastrinoma-associated excessive progastrin tissue concentrations led to diminished expression of E-cadherin within the gastric mucosa and promoted tumor development of a signet-ring cell carcinoma.
胃神经内分泌肿瘤是一种罕见的肿瘤，起源于胃体黏膜中的胃嗜铬样（ECL）细胞。胃泌素及其衍生物已被报道可调节上皮细胞的增殖、迁移和分化。上皮钙黏蛋白（E-cadherin）基因的突变已被证明与受影响家族中弥漫性胃癌的发生有关。
在本研究中，我们调查了一名患有1型多发性内分泌肿瘤且伴有恶性十二指肠胃泌素瘤和多发性胃ECL细胞瘤的患者，该患者还发生了胃印戒细胞癌，其胃肠道壁的组织病理学和分子学发现。
对一名1型多发性内分泌肿瘤患者的胃肠道活检组织进行囊泡单胺转运体-2和E-cadherin免疫染色。使用与前胃泌素、甘氨酸延伸型胃泌素和酰胺化胃泌素反应的抗体，测定患者血清中的非酰胺化胃泌素产物。进行基因分析以排除E-cadherin基因中的种系突变。
胃ECL细胞瘤的免疫组织化学研究显示，与胃表面黏膜细胞相比，E-cadherin表达大幅减少，印戒细胞癌的细胞中E-cadherin表达缺失。详细的生化测量显示，血浆中前胃泌素浓度约为酰胺化胃泌素浓度的20%，甘氨酸胃泌素浓度约为10%。分子分析未发现E-cadherin种系突变。
我们的免疫组织化学研究可能表明，胃泌素瘤相关的前胃泌素组织浓度过高导致胃黏膜中E-cadherin表达减少，并促进了印戒细胞癌的肿瘤发展。
