Anlauf M, Perren A, Klöppel G
Institut für Pathologie, Universitätsklinikum S-H, Campus Kiel.
Verh Dtsch Ges Pathol. 2007;91:320-9.
The identification of precursor lesions has a great impact on our understanding of tumorigenesis. In this study we investigated whether preneoplastic lesions can be identified in sporadic gastrinomas and in gastrinomas in multiple endocrine neoplasia type 1 (MEN1) patients. These lesions were tested for loss of heterozygosity (LOH) of the MEN1 gene locus on chromosome 11q13.
Tissue specimens from 25 patients with Zollinger-Ellison syndrome (ZES) were analyzed. The MEN1 status was assessed clinically and by mutational analysis. For simultaneous analysis of hormones and allelic deletions a combined FISH fluorescence in situ hybridization/immunofluorescence protocol was established.
Hyperplastic gastrin cell lesions were present in the nontumorous mucosa of all MEN1 patients, but not in 12 patients with sporadic duodenal gastrinomas. The hyperplastic gastrin cells retained both 11q13 alleles. 11q13 LOH was, however, detected in duodenal gastrinomas, some as small as 300 microm in diameter, in 13 patients with MEN1.
MEN1-associated duodenal gastrinomas, but not sporadic gastrinomas, are associated with gastrin cell hyperplasia. It is therefore likely that hyperplastic gastrin cell lesions precede the development of MEN1-associated duodenal gastrinomas. Allelic deletion of the MEN1 gene locus may reflect a decisive initial event in the development of multifocal MEN1-associated gastrinomas from hyperplastic gastrin cell lesions.
前驱病变的识别对我们理解肿瘤发生有重大影响。在本研究中，我们调查了散发性胃泌素瘤和1型多发性内分泌肿瘤（MEN1）患者的胃泌素瘤中是否能识别出癌前病变。对这些病变进行了11号染色体q13区域MEN1基因座杂合性缺失（LOH）检测。
分析了25例卓艾综合征（ZES）患者的组织标本。通过临床评估和突变分析来评估MEN1状态。为同时分析激素和等位基因缺失，建立了一种联合荧光原位杂交/免疫荧光检测方法。
所有MEN1患者的非肿瘤性黏膜中均存在胃泌素细胞增生性病变，但12例散发性十二指肠胃泌素瘤患者中未发现。增生的胃泌素细胞保留了两个11q13等位基因。然而，在13例MEN1患者的十二指肠胃泌素瘤中检测到11q13 LOH，有些肿瘤直径小至300微米。
MEN1相关的十二指肠胃泌素瘤而非散发性胃泌素瘤与胃泌素细胞增生有关。因此，增生性胃泌素细胞病变可能先于MEN1相关的十二指肠胃泌素瘤发生。MEN1基因座的等位基因缺失可能反映了增生性胃泌素细胞病变发展为多灶性MEN1相关胃泌素瘤过程中的一个决定性初始事件。
