Molecular Pathology of Gastric Carcinoma

Abstract

Gastric carcinoma (GC) is a biologically heterogeneous disease involving numerous genetic and epigenetic alterations. A very small proportion of GCs can be caused by a specific germ-line mutation of the E-cadherin gene (CDH1). Sporadic GC is developed through multistep processes that begin with Helicobacter pylori-induced atrophic gastritis. Epstein-Barr virus is another infectious cause of GC, and the above two infection-associated GCs are characterized by global CpG island methylation in the promoter region of cancer-related genes. Mutations of tumor protein p53 (TP53) and β-catenin (CTNNB1) genes occur early in the development of GC and contribute to gastric carcinogenesis. Furthermore, significant numbers of GCs show loss of Runx3 due to hemizygous deletion and hypermethylation of the promoter region. Aberrant Cdx2 expression has been shown in precancerous lesions as well as GC. However, it remains unclear whether Cdx2 plays an oncogenic role in gastric carcinogenesis. GC with microsatellite instability is also a well-defined subset exhibiting distinctive clinicopathologic features. Targeted therapy against GC with ERBB2 amplification recently improved the prognosis of patients with advanced GC. In addition, epigenetic changes in GC could be attractive targets for cancer treatment with modulators. A genome-wide search has been undertaken to identify novel methylation-silenced genes in GC, which will help us understand the overall molecular features of GC and further provide novel opportunities in the treatment of GC.

Protein arginine methyltransferase 5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer

“…The high mortality of GC is explained by our poor understanding of its mechanism of progression and the lack of suitable diagnostic markers that hinder diagnosis before the disease reaches an advanced stage (7,8). GC represents a biologically and genetically heterogeneous group of tumours that are induced by multiple factors that deregulate cell signalling pathways, which leads to the acquisition of malignant phenotypes such as increased cell proliferation, inhibition of apoptosis and enhanced invasiveness (9)(10)(11). Identification of novel molecules is therefore required to improve diagnosis and therapy.…”

Prognostic impact of expression and methylation status of DENN/MADD domain-containing protein 2D in gastric cancer

“…Gastric cancer (GC) is one of the most common malignant tumors and the second most common cause of cancer death worldwide, although there has been a steady decline in the incidence and mortality risk of GC over several decades in most countries [1,2]. However, advanced GCs are still likely to have an adverse prognosis as a result of early recurrence and distal metastasis, even after curative resection [3].…”

Clinicopathologic features of gastric cancer with synchronous and metachronous colorectal cancer in Korea: are microsatellite instability and p53 overexpression useful markers for predicting colorectal cancer in gastric cancer patients?

“…If the DNA damage cannot be repaired, p53 induces apoptosis [38]. Therefore, direct mutations of the p53 gene or a loss of p53 function by its regulators allows a cell with damaged DNA to escape from normal growth, resulting in cancer development [39]. Because of the increased half-life of the mutant p53 protein compared with the wild-type p53, immunochemical overexpression of p53 protein in tumors has been interpreted as a surrogate for p53 mutation.…”