Clinical implications of E-cadherin associated hereditary diffuse gastric cancer

Approximately 1-3% of gastric cancers arise as a result of inherited gastric cancer predisposition syndromes. These may be of the diffuse or intestinal type. Linkage analysis has recently implicated E-cadherin mutations in an estimated 25% of families with an autosomal dominant predisposition to diffuse type gastric cancers. This subset of gastric cancer has been termed hereditary diffuse gastric cancer (HDGC).     

E-cadherin molecular expresion in the diffuse and intestinal types of gastric adenocarcinoma. A report from Lima, Peru]

OBJECTIVE: Signet ring carcinoma of the stomach is well known to be more aggressive and infiltrating than adenocarcinoma. Different studies have proposed that signet ring cell carcinoma would be more infiltrating because of the loss of E-cadherin expression, this cadherin is a class of protein cell membrane protein which plays an important role in cell-adhesion. METHODS: We carried out a transversal comparative study, in order to measure the E-cadherin expression in 10 cases of signet ring cell and in 10 cases of adenocarcinoma, with help of immunohistochemistry. RESULTS: We found a bigger expression of E-cadherin in adenocarcinomas (100%) than signet ring cell carcinoma (40%), this difference was significative using Fisher test (p = 0,011). The loss of E-cadherin would explain the bigger infiltrating capacity in comparison to adenocarcinoma.     

Metachronous gastric diffuse large B-cell lymphoma and adenocarcinoma.

The development of gastric carcinoma in a patient with gastric lymphoma is rare. Helicobacter pylori is a common etiologic agent for both these conditions. We report a 38-year-old lady who was initially diagnosed to have gastric lymphoma and developed early gastric carcinoma on follow up. She was operated on for the carcinoma and is in complete remission since.     

上皮型钙黏素基因启动子甲基化与胃肠腺癌的关系及意义

目的探讨上皮型钙黏素（E—cad）基因启动子CpG岛甲基化与胃腺癌（GAC）和大肠腺癌（CRAC）的关系及意义。方法用甲基化特异性PCR技术检测82例GAC组织（GAC组）、30例十二指肠球部溃疡胃窦黏膜组织（对照组）、30例慢性胃炎伴肠上皮化生或异型增生胃黏膜组织（胃炎组）、94例CRAC组织（CARC组）及其癌旁非肿瘤组织中的E—cad基因启动子CpG岛甲基化状况。结果GAC组E—cad甲基化率显著高于对照组和胃炎组（P〈0．01,〈0．05）,低分化者显著高于高、中分化者（P〈0．05）,Ⅲ～Ⅳ期肿瘤显著高于Ⅰ～Ⅱ期（P〈0．05）CRAC组显著高于癌旁非肿瘤组织（P〈0．01）。结论E—cad基因启动子CpG岛甲基化可能参与胃肠腺癌发生。     

贲门腺癌组织中RKIP、E-cadherin的表达变化及相关性

目的 观察Raf激酶抑制蛋白（RKIP）、上皮型钙黏蛋白（E-cadherin）在贲门腺癌组织中的表达变化,并探讨其相关性.方法 应用免疫组化SP法检测160例贲门腺癌组织及癌旁非肿瘤组织中RKIP、E-cadherin的蛋白表达情况,分析其表达与临床病理参数的关系以及两者表达的相关性.结果 RKIP和E-cadherin在贲门腺癌组织中表达明显低于癌旁组织（P均＜0.05）.RKIP和E-cadherin在高分化、中分化和低分化的贲门腺癌组织中的表达差异有统计学意义（P均＜0.01）,在有淋巴结转移的贲门腺癌组织中表达低于无淋巴结转移的组织（P均＜0.05）.RKIP和E-cadherin在贲门腺癌组织中的表达呈正相关（r=0.388,P＜0.05）.结论 RKIP和E-cadherin 在贲门腺癌组织中表达降低,且两者表达呈正相关.     

Confocal laser endomicroscopy diagnosis of gastric adenocarcinoma in a patient treated for gastric diffuse large-B-cell lymphoma

The association between gastric carcinoma and lymphoma is rare. Confocal laser endomicroscopy is a new diagnostic tool that allows the identification of cellular and vascular architecture during endoscopy. This is the first report of an in vivo early gastric carcinoma diagnosis by confocal laser endomicroscopy in a patient successfully treated for a primary gastric diffuse large-B-cell lymphoma.     

E-cadherin in gastric cancer

Cadherin is an adhesion molecule and a superfamily of calcium-mediated membrane glycoproteins. E-cadherin is the prototype of the class E-cadherin that links to catenins to form the cytoskeleton. Recent evidence has shown that E-cadherin not only acts as an adhesive, but also plays important roles in growth development and carcinogenesis. It has been recently viewed as an invasion as well as a growth suppressor gene. This review summarizes the recent discoveries on E-cadherin and its role in gastric cancer. In particular, our work on E-cadherin in gastric cancer, including its relation with Helicobacter pylori and clinical applications, are described in detail.     

Synchronous diffuse well-differentiated lymphocytic lymphoma and gastric adenocarcinoma presenting as splenomegaly and iron deficiency anemia

Diffuse well-differentiated lymphocytic lymphoma (D-WDLL) and chronic lymphocytic lymphoma (CLL) represent closely related neoplasms which may have indolent courses. Dating back more than one century, reports of associated second primary malignancies continue to intrigue clinicians. A case of synchronous D-WDLL and gastric adenocarcinoma, presenting as splenomegaly and iron deficiency anemia, is presented. The case and literature are reviewed.     

Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families.

BACKGROUND & AIMS: Germline mutations in CDH1 are known to cause hereditary diffuse gastric cancer (HDGC). Breast and colorectal cancer have also been reported in CDH1-associated HDGC. The purpose of this study was to estimate the cumulative risk of gastric and breast cancer in CDH1 mutation carriers. METHODS: Family data were collected by member groups of the International Gastric Cancer Linkage Consortium. Eligible families had at least 3 cases of diffuse gastric cancer, and at least 1 affected member had tested positive for a mutation in CDH1. Eleven families met these criteria. We used the pedigree information to estimate penetrance using the MENDEL program. The conditional likelihood of the pedigree was maximized given the phenotype of the pedigree and genotype of the index case at ascertainment. We parameterized the model in terms of log relative risks for mutation carriers compared with risks in the general population of the United Kingdom. Noncarriers of the gene were assumed to develop the disease at population incidence rates. RESULTS: The estimated cumulative risk of gastric cancer by age 80 years was 67% for men (95% confidence interval [95% CI], 39-99) and 83% for women (95% CI, 58-99). For women, the cumulative risk of breast cancer was 39% (95% CI, 12-84). The combined risk of gastric cancer and breast cancer in women was 90% by age 80 years. CONCLUSIONS: These penetrance estimates should be useful for genetic counseling in multiple-case families. However, they may not apply to individuals with a minimal family history, in whom the risks may be lower.     

Synchronous gastric adenocarcinoma and pancreatic ductal adenocarcinoma

BACKGROUND:The association between gastric and pancreatic carcinoma is a relatively rare condition.In gastric carcinoma patients,the prevalence of second tumors varies 2.8% to 6.8% according to the reported statistics.Gastric cancer associated with pancreatic cancer is uncommon.METHODS:We report a case of a 73-year-old patient hospitalized for vomiting and weight loss.Esophagogastroduodenoscopy demonstrated an ulcerative lesion of the gastric antrum.Computed tomography and magnetic resonance showed a gastri...     

胃腺癌患者舌苔变化及其血清sE-cad水平和临床检验指标的相关性

目的:探讨胃腺癌患者和正常人的舌苔形成与血清sE-cad水平的相关性.方法:采用临床病例-对照法,应用ELISA测定266例胃腺癌患者和252例对照人群的血清sE-cad水平,非参数检验分析血清sE-cad水平、临床检验指标和舌苔类型的相关性.结果:胃腺癌组血清sE-cad水平显著高于对照组(P<0.01),术前者血清sE-cad水平显著高于术后者(P<0.05),胃腺癌未转移者血清sE-cad水平显著高于转移者(P<0.05).胃腺癌组血清sE-cad水平表现为白厚苔>白薄苔>黄厚苔>黄薄苔>剥苔,有统计学意义(P<0.05),对照组血清sE-cad水平表现为黄薄苔>黄厚苔>白薄苔>白厚苔>剥苔,但无统计学意义(P>0.05).胃腺癌组临床检验指标异常者比例均高于对照组(P<0.05),特别是总蛋白异常的厚苔、薄苔胃腺癌患者的血清sE-cad水平均高于总蛋白异常的厚苔、薄苔对照组(P<0.05).结论:胃腺癌患者苔质厚薄变化、血清总蛋白和sE-cad水平检测对临床胃腺癌防治可能有重要的临床价值.     

New subtype of gastric adenocarcinoma: mixed fundic and pyloric mucosa-type adenocarcinoma

A 73-year-old woman underwent upper endoscopic screening that revealed a 30-mm superficial elevated lesion in the anterior wall of the upper gastric body. The lesion had a whitish color and coarse granular surface in conventional white light endoscopy. Magnifying narrow-band imaging indicated irregular microvascular and microsurface patterns within a demarcation line. The microvessels had a distorted polygonal shape within the area surrounded by the marginal crypt epithelium. The patient underwent endoscopic resection. Histological examination of the resected specimen showed a very well- to well-differentiated tubular adenocarcinoma with differentiation toward the mixed fundic and pyloric mucosa, without chief cells. The histological and serological findings indicated the absence of Helicobacter pylori infection. The present case demonstrates a new histological subtype of gastric adenocarcinoma, which has characteristic endoscopic findings.     

Hereditary diffuse gastric cancer

Some diffuse type gastric cancers are of hereditary origin. Their histological characteristics are poor cell differentiation and the presence of signet-ring cells. The cause is a mutation of the CDH1 gene which is responsible for abnormal E-cadherin. The transmission mode is autosomal dominant. Because of serious prognosis of symptomatic hereditary diffuse gastric cancer (HDGC), the high penetrance of the gene (67% in men and 83% in women) and the young age of onset of these tumors (before the age of 40), a prophylactic gastrectomy is recommended to the mutation carriers. The search for the genetic mutation should be recommended to families corresponding to clinical criteria such as the number of affected family members, degree of relationship and age of onset of these tumors.     

Hereditary diffuse gastric cancer: diagnosis and management.

Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome defined by germline mutation of the E-cadherin gene (CDH-1). The cumulative risk for advanced gastric cancer in HDGC is 67% in men and 83% in women by 80 years of age. Early HDGC is characterized by multiple microscopic foci of intramucosal signet-ring cell carcinoma. The time to progression of these foci appears to be variable and currently is not predictable--the carcinoma foci may remain confined to the mucosa for many years. The management options for mutation carriers include prophylactic gastrectomy or surveillance gastroscopy. The only extensive published surveillance experience used chromogastroscopy, which detected early HDGC foci not visible on white-light endoscopy. The use of new techniques such as confocal microscopy, spectroscopy, or autofluorescence may prove useful, but have not been studied in HDGC. In patients up to 20 years of age, the risk for gastric cancer is less than 1%; this risk is outweighed by the mortality and morbidity associated with total gastrectomy. It is therefore recommended that genetic testing should occur at 16 years of age and that annual surveillance chromogastroscopy also should begin at age 16 in identified CDH-1 mutation carriers. After 20 years of age, delaying prophylactic gastrectomy carries significant risk, particularly if the alternative is surveillance by white-light gastroscopy. Surveillance chromogastroscopy (Congo red/methylene blue technique) should be considered for individuals younger than 20 years and patients unwilling to undergo prophylactic gastrectomy. Sufficient evidence for an increased risk for lobular breast cancer in CDH-1 carriers exists to justify breast screening in female carriers older than 35 years of age, however, evidence is insufficient to recommend prophylactic mastectomy.     

MYC and gastric adenocarcinoma carcinogenesis

MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacterpylori （Hpylon] and clinical applications.     

Synchronous gastric adenocarcinoma and carcinoid

We report the rare case of a 68-year-old man who had two separate and histologically dissimilar gastric tumors: a poorly differentiated adenocarcinoma and a carcinoid. The latter tumor showed argyrophilic granules (Grimelius technique) and positivity for chromogranin A and neuron-specific enolase stains, confirming the neuroendocrine nature of the neoplasia. The literature concerning this subject is reviewed.     

E-钙黏蛋白与胃癌关系的研究进展

E-钙黏蛋白(E-cadherin,E-cad)是跨膜糖蛋白家族的一员,正常表达于上皮细胞,介导Ca2-依赖的细胞-细胞黏附,对维持组织结构和形态形成十分重要.转移是恶性肿瘤最具破坏性的特征,也是肿瘤患者死亡的主要原因.因此,以肿瘤的扩散和转移为靶向的研究在肿瘤治疗中起重要作用.本文就近年来关于E-cad在胃癌方面的研究作一概述.