Gastric cancer: New genetic developments

Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Journal of Surgical Oncology (Impact Factor: 2.84). 05/2005; 90(3):114 - 133. DOI: 10.1002/jso.20214

ABSTRACT Gastric cancer's (GC) incidence shows large geographic differences worldwide with the lowest rates occurring in most Western industrialized countries including the United States and the United Kingdom; in contrast, relatively high rates of GC occur in Japan, Korea, China, and South America, particularly Chile. The Laurén classification system classifies GC under two major histopathological variants: 1) an intestinal type and 2) a diffuse type. The intestinal type is more common in the general population, more likely to be sporadic and related to environmental factors such as diet, particularly salted fish and meat as well as smoked foods, cigarette smoking, and alcohol use. It exhibits components of glandular, solid, or intestinal architecture, as well as tubular structures. On the other hand, the diffuse type is more likely to have a primary genetic etiology, a subset of which, known as hereditary diffuse gastric cancer (HDGC), is due to the E-cadherin (CDH1) germline mutation. The diffuse type pathology is characterized by poorly cohesive clusters of cells which infiltrate the gastric wall, leading to its widespread thickening and rigidity of the gastric wall, known as linitis plastica. Helicobacter pylori infection is associated with risk for both the intestinal and diffuse varieties of gastric cancer. Germline truncating mutations of the CDH1 gene, which codes for the E-cadherin protein, were initially identified in three Maori families from New Zealand that were predisposed to diffuse GC. Since then, similar mutations have been described in more than 40 additional HDGC families of diverse ethnic backgrounds. It is noteworthy that two-thirds of HDGC families reported to date have proved negative for the CDH1 germline mutation. A number of candidate genes have been identified through analysis of the molecular biology of E-cadherin. Patients with evidence of the CDH1 germline mutation in the context of a family history of HDGC must be considered as candidates for prophylactic gastrectomy, given the extreme difficulty in its early diagnosis and its exceedingly poor prognosis when there is regional or distant spread. Specifically, the E-cadherin cytoplasmic tail interacts with catenins, assembling the cell-adhesion complex involved with E-cadherin mediated cell:cell adhesion. β-catenin and γ-catenin compete for the same binding site on the E-cadherin cytoplasmic tail, directly linking the adhesion complex to the cytoskeleton through α-catenin. β-catenin gene (CTNNB1) mutations have been described predominantly in intestinal-type gastric cancers and CTNNB1 gene amplification and overexpression have recently been described in a mixed-type gastric cancer. This paper reviews the genetics of both intestinal and diffuse types of gastric carcinoma, their differential diagnosis, molecular genetics, pathology, and, when known, their mode of genetic transmission within families. J. Surg. Oncol. 2005;90:114–133. © 2005 Wiley-Liss, Inc.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ZET Mide kanseri dünyadaki en yaygin malignitelerden biridir. Fakat etyolojisi tam olarak açiklanamamistir ve insidansi bariz cografi varyasyonlar gösterir. Bu yazimizda 17 yasinda, tedaviye dirençli karin agrisi sebebiyle klinigimize müracaat eden hastayi inceledik. Laboratuvar tetkilerinde anemi disinda özellik yoktu. Yapilan endoskopik muayenesinde mide kanseri t anisi kondu. Mide kanseri ileri yas hastaligidir, fakat özellikle mide kanserinin endemik görüldügü bölgelerde, tedaviye yanitsiz dispeptik sikayetleri olan hastalarda ayirici teshiste akilda bulundurulmalidir. ABSTRACT A Gastric Cancer Case In Young Patient Gastric cancer is one of the most frequent malignant diseases in t he worldwide, b ut the etiology remains unclear, and there are marked geographical divergences in the prevalence. We here present a 17-year old female case who was admitted to our clinic due to abdominal pain. Laboratory tests were normal except anemia findings. Gastric cancer was diagnosed in the endoscopic examination. Gastric cancer is an elderly disease, but, especially in endemic regions, it should be taken into consideration in the differential diagnosis in patients with dyspeptic symptoms being resistant to therapy.
  • Source
    Life Science Journal. 01/2013; 10(12s):212-216.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The prognostic significance of CD24 expression for survival in patients with gastric cancer remains controversial. We conducted a meta-analysis to investigate the impact of CD24 expression on clinicopathological features and survival outcomes in gastric cancer. A comprehensive literature search of the electronic databases PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI; up to April 8, 2014) was performed for relevant studies using multiple search strategies. Correlations between CD24 expression and clinicopathological features and overall survival (OS) were analyzed. A total of 1,041 patients with gastric cancer from 9 studies were included. The pooled odds ratios (ORs) indicated CD24 expression was associated with tumor depth (OR = 0.45, 95% confidence interval [CI] = 0.32-0.63; P<0.00001), status of lymph nodes (OR = 0.40, 95% CI = 0.25-0.64; P = 0.0001) and tumor node metastasis (TNM) stage (OR = 0.56, 95% CI = 0.41-0.77; P = 0.0003). The pooled hazard ratio (HR) for OS showed overexpression of CD24 reduced OS in gastric cancer (HR = 1.99, 95% CI = 1.29-3.07, P = 0.002). Whereas, combined ORs showed that CD24 expression had no correlation with tumor differentiation or Lauren classifications. CD24 overexpression in patients with gastric cancer indicated worse survival outcomes and was associated with common clinicopathological poor prognostic factors.
    PLoS ONE 01/2014; 9(12):e114746. · 3.53 Impact Factor