E-Cadherin and Gastric Cancer

Gastric cancer is one of the most common cancers in the world. Gastric cancer is the third leading cause of cancer associated death worldwide. The prognosis of gastric carcinoma is poor. Gastric carcinoma is a silent disease and often patients are not aware of their disease until reaching the end stages. Symptoms include weight loss, abdominal pain, vomiting, dysphasia, melena and altered bowel function. There are two main histological types of GC according to the World Health Organization (WHO) and the Lauren classifications, diffuse gastric cancer and intestinal gastric cancer. Intestinal gastric cancer is more associated with environmental factors such as infection of H. pylori, high salty diet, smoking, and obesity, while diffuse gastric cancer is composed by noncohesive cells and is more commonly observed in younger patients, with an obvious hereditary form.

The CDH1 gene encodes for E-cadherin. Cadherins are transmembrane glycoproteins that mediate the Calcium-dependent cell-cell adhesion. They are the major part of the adherent junctions and result in the epithelial barrier integrity between the adjacent cells. Also, studies show that the development of human carcinomas is often associated with the loss or mutation of the E-cadherins. Selective loss of E cadherin can cause invasive carcinomas. E-cadherin acts as a tumor suppressor and downregulation of E-cadherin is
observed in various cancers. Somatic mutations of CDH1 have been identified in sporadic diffuse gastric cancer, colorectal cancer, lobular breast cancer, and ovarian cancer.

Clinical Applications of E-Cadherin in Gastric Cancer
Evaluation of expression of E-cadherin or alterations in its encoded CDH1 gene may provide promising applications for diagnosis, prognosis, or therapeutic targets for gastric cancer.

  • Soluble E-cadherin may serve as a prospective tumor marker that accurately reflects the progressive regeneration of E-cadherin at tumor sites. Furthermore, analysis of soluble E-cadherin in serum and cancer tissue provides hints for elucidating the mechanism of decrease of E-cadherin in cancer cells. Moreover, high concentration of soluble E cadherin in the serum of patients with gastric cancer predicts tumor T4 depth invasion and poor survival, suggesting that E-cadherin could be applied as a valid prognostic marker for gastric cancer. It has also been revealed that high levels of soluble E-cadherin in serum 3 to 6 months after curative surgery could predict recurrence of gastric carcinoma. The evidence mentioned above indicates that soluble E-cadherin could serve as a potential biomarker in diagnosis, prognosis, and tumor recurrence of gastric cancer.
  • As germ line mutation in E-cadherin (CDH1) gene was strongly involved in hereditary diffuse gastric cancer (HDGC)
  • Individuals without CDH1 mutation should take clinical surveillance by EGD (oesophagogastroduodenoscopy), while the ones with CDH1 high risk missense mutations or truncating mutations was strongly recommended to take prophylactic gastrectomy and under close follow-up
  • Methylation of CDH1 has been reported to be regulated by H. pylori infection in chronic gastritis and intestinal metaplasia patients, indicating that Ecadherin plays an important role in gastric cancer initiation. Importantly, eradication of H. pylori infection is able to reverse the hypermethylation status of CDH1, thus delaying or reversing H. pylori induced gastric carcinogenesis.

Dr.Orkhan FARMANLI, MD
Surgical Pathologist, Istanbul/ Turkey