Mdm2 gene amplification in gastric cancer correlation with expression of mdm2 protein and p53 alterations
Mdm2 gene amplification in gastric cancer correlation with expression of mdm2 protein and p53 alterations
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DOI：
10.1038/modpathol.3880107
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发表时间：
2000-06-01
期刊：
影响因子：
7.5
通讯作者：
Roessner, A
中科院分区：
文献类型：
--
作者：
Günther, T;Schneider-Stock, R;Roessner, A
Mdm2位于12号染色体上，被认为是p53功能的负调节因子，似乎在多种肿瘤的发病机制中发挥作用。Mdm2在晚期胃癌中的扩增尚未被研究，在43例胃癌中检测到Mdm2扩增，其遗传结果与Mdm2蛋白表达、p53改变和临床病理数据相关。肿瘤根据Lauren分类：20例肠型肿瘤，19例弥漫生长包括原发性小细胞癌，4例混合分化癌。根据pTNM分类系统进行分期。肿瘤组织经福尔马林固定和石蜡包埋后，免疫组织学检测Mdm2和p53。用mdm2 cDNA探针对肿瘤DNA进行非放射性杂交扩增mdm2致癌基因。用密度学方法评估Southern印迹。对于p53突变筛选，我们使用聚合酶链反应-单链构象多态性技术分析了p53基因的高度保守区域（外显子4至8）。带移位聚合酶链反应产物直接测序。Mdm2扩增18例（41.8%）。mdm2基因在弥漫性肿瘤中扩增的频率更高，而肠型胃癌中p53基因的改变频率更高。mdm2/p53状态的分子遗传学和免疫组织学结果与患者的分期、年龄和性别无统计学意义。mdm2/p53通路是胃癌发生的一部分，只有约20%的胃癌未表现出mdm2和/或p53的改变。mdm2癌基因的上调和伴随的肿瘤抑制基因53的失活似乎在弥漫性癌中起着重要作用。
Mdm2, localized on chromosome 12, is considered a negative regulator of p53 function and seems to play a role in the pathogenesis of a variety of tumors, The mdm2 amplification in advanced-stage gastric carcinoma has not yet been investigated,Mdm2 amplification was determined in 43 gastric carcinomas, and the genetic results were correlated with mdm2 protein expression, p53 alterations, and clinicopathologic data. The tumors were classified according to Lauren: 20 intestinal-type tumors, 19 tumors of diffuse growth inclusive of a primary small cell carcinoma, and 4 carcinomas with mixed differentiation. Staging was based on the pTNM classification system. Mdm2 and p53 were demonstrated by immunohistology on formalin-fixed and paraffin-embedded tumor tissue. The mdm2 oncogene was amplified by nonradioactive hybridization of tumor DNA with an mdm2 cDNA probe. The Southern blots were evaluated densitometrically. For p53 mutation screening, we analyzed the highly conservative regions of the p53 gene (exons 4 to 8) with the use of the polymerase chain reaction-single-strand conformation polymorphism technique. Polymerase chain reaction products with band shifting were directly sequenced.Mdm2 amplification was demonstrated in 18 tumors (41.8%). The mdm2 gene was amplified more frequently in carcinomas with a diffuse growth pattern, Gastric carcinomas of the intestinal type, however, showed a higher frequency of p53 alterations. There was no statistical significance of the molecular genetic and immunohistologic results of the mdm2/p53 status to staging as well as to age and sex of the patients.The mdm2/p53 pathway is a part of the carcinogenesis of gastric carcinoma Only approximately 20% of gastric carcinomas failed to show mdm2 and/or p53 alterations. The upregulation of the mdm2 oncogene and the accompanying inactivation of the tumor suppressor gene 53 seem to play a role above all in carcinomas of the diffuse type.