Precursor lesions in patients with multiple endocrine neoplasia type 1-associated duodenal gastrinomas
Precursor lesions in patients with multiple endocrine neoplasia type 1-associated duodenal gastrinomas
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DOI：
10.1053/j.gastro.2005.01.058
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发表时间：
2005-05-01
期刊：
影响因子：
29.4
通讯作者：
Klöppel, G
中科院分区：
文献类型：
--
作者：
Anlauf, M;Perren, A;Klöppel, G
背景与目的：前驱病变的识别对理解肿瘤发生有很大影响。已知内分泌肿瘤的前驱病变发生在 MEN1 综合征的情况下。本研究的目的是检验 MEN1 相关十二指肠胃泌素瘤起源于弥漫性癌前胃泌素细胞变化的假设。前驱病变可能先于十二指肠胃泌素瘤的发展，因为与散发性胃泌素瘤相比，这些肿瘤通常是多发的。方法：对25例十二指肠胃泌素瘤手术患者的十二指肠非肿瘤组织中内分泌细胞的分布进行定性和定量分析。 MEN1 状态通过临床评估和基于聚合酶链反应的突变分析进行评估。结果：25 名胃泌素瘤患者中有 14 名在非肿瘤性十二指肠粘膜中出现由胃泌素细胞组成的增殖性增生性病变，类似于慢性萎缩性胃炎中观察到的胃肠嗜铬样细胞病变。所有经证实具有 MEN1 的佐林格-埃利森综合征患者均具有此类增殖性胃泌素细胞病变，而所有无前驱病变的佐林格-埃利森综合征患者均为 MEN1 阴性。结论：MEN1 中的十二指肠胃泌素瘤（而非散发性十二指肠胃泌素瘤）与非肿瘤粘膜内的增殖性胃泌素细胞变化相关。这些病变很可能先于 MEN1 相关十二指肠胃泌素瘤的发展。
Background & Aims: The identification of precursor lesions has a great impact on the understanding of tumorigenesis. Precursor lesions of endocrine tumors are known to occur in the setting of the MEN1 syndrome. The aim of this study was to test the hypothesis that MEN1-associated duodenal gastrinomas originate from diffuse preneoplastic gastrin cell changes. Precursor lesions may precede the development of duodenal gastrinomas because, in contrast to sporadic gastrinomas, these tumors are usually multiple. Methods: The distribution of endocrine cells in the nontumorous duodenal tissue was analyzed qualitatively and quantitatively for 25 patients operated on for a duodenal gastrinoma. MEN1 status was assessed clinically and by polymerase chain reaction-based mutational analysis. Results: Fourteen of 25 patients with gastrinoma had proliferative, hyperplastic lesions consisting of gastrin cells in the nontumorous duodenal mucosa, similar to the gastric enterochromaffin-like cell lesions observed in chronic atrophic gastritis. All patients with Zollinger-Ellison syndrome with proven MEN1 had such proliferative gastrin cell lesions, and all patients with Zollinger-Ellison syndrome without precursor lesions were MEN1 negative. Conclusions: Duodenal gastrinomas in MEN1, but not sporadic duodenal gastrinomas, are associated with proliferative gastrin cell changes within the nontumorous mucosa. It is likely that these lesions precede the development of MEN1-associated duodenal gastrinomas.