E-Cadherin expression in Sporadic Gastric cancer from Mexico:: Exon 8 and 9 deletions are infrequent events associated with poor survival

E-Cadherin expression in Sporadic Gastric cancer from Mexico:: Exon 8 and 9 deletions are infrequent events associated with poor survival
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DOI:
10.1016/j.humpath.2004.09.020
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发表时间:
2005-01-01
期刊:
影响因子:
3.3
通讯作者:
Fend, F
Fend, F
中科院分区:
医学3区
文献类型:
--
作者:
Gamboa-Dominguez, A;Dominguez-Fonseca, C;Fend, F

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F-钙粘蛋白的异常表达和突变在胃癌尤其是弥漫型胃癌中较为常见。CDH1(编码E-钙粘素基因)突变在弥漫性胃癌高发人群中的频率及其预后意义尚不清楚。177例来自墨西哥混合症患者的胃扭转包括肠型(53例)、混合型(55例)或弥漫型(69例)GC。此外,对101例未经手术的胃癌患者的内窥镜活检进行了分析。对野生型E-钙粘蛋白(克隆36)和识别缺失外显子8(Del 8)或外显子9(Del 9)的突变型CDHI的2种突变特异性抗体(MSA)进行免疫组织化学染色。染色与组织类型、肿瘤转移分期及随访有关。84%的胃癌中Ecad表达异常或缺失(克隆值为36),以弥漫性或混合性肿瘤为主(P=0.004),晚期(P=0.003)。在野生型E-钙粘素表达正常、异常或缺失的患者中,1年和2年的生存期没有差异。在接受手术治疗的10名患者(5.6%)中观察到对MSA的总体反应性。在140例死亡者和存活者中,del819阳性患者的1年和2年生存率分别为37%和17%,14%和0(对数等级P=0.01)。来自不能手术的GC(101)患者的活检组织中有5例(4.95%)呈del 8或9免疫反应。E-钙粘附素在胃癌中的异常表达较为常见。然而,在来自墨西哥的这一系列肿瘤中,只有5.3%的人观察到外显子8或9的缺失,这一比例低于先前发表的比例,但与更差的预后相关。(C)2005 Elsevier Inc.保留所有权利。
Aberrant expression and mutation of F-cadherin is frequent in gastric carcinoma (GC) especially of the diffuse type. The frequency of CDH1 (gene encoding E-cadherin) mutation in populations with high incidence of diffuse GC and its prognostic significance is unknown. One hundred seventy-seven gastrectornies from Mexican mestizo patients with intestinal (53), mixed (55), or diffuse (69) GC were included. In addition, 101 endoscopic biopsies from patients with GC not subjected to surgery were analyzed. Immunohistochemistry against wild-type E-cadherin (clone 36) and against 2 mutation-specific antibodies (MSA) recognizing mutant CDHI lacking exon-8 (del 8) or exon-9 (del 9) were performed. Staining was correlated with histotype, tumor node metastasis stage, and follow-up. Abnormal or absent Ecadherin expression (clone 36) was identified in 84% GC, predominantly in diffuse or mixed tumors (P = 0.004) in advanced stages (P = 0.003). No survival differences at I and 2 years were observed among patients showing normal, abnormal, or absent wild type E-cadherin expression. Overall reactivity with the MSA was observed in 10 (5.6%) patients who were treated with surgery. In 140 patients, dead from the disease or alive with the disease, the survival at 1 and 2 years was 37% versus 17% and 14% versus 0 for patients without and with del 819 positivity, respectively (log rank P = 0.01). Biopsies from patients with inoperable-GC (101) rendered 5 (4.95%) with del 8 or 9 immunoreactivity. Abnormal E-cadherin expression is frequent in GC. However, exon 8 or 9 deletions were observed in only 5.3% tumors in this series from Mexico, at a lower rate than previously published, but associated with a worse prognosis. (C) 2005 Elsevier Inc. All rights reserved.