Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

The aberrant expression of beta-catenin in esophageal squamous cell cancer (ESCC) in Northeastern Iran

Purpose/Objective(s): The esophagus squamous cell cancer has very high incidence among Northeastern Turkmen tribes of Iran. This population traces its ancestry back to East Asian tribes who migrated to Iran in 12th Century. Genetic as well as environmental factors have been contemplated as the causes of this highly malignant disease. The pathophysiology as well as the genetic causes of this disease remains vastly unknown. Alteration in Wnt signaling/beta-catenin pathway has been associated with several solid tumors. Two of the beta-catenin target genes, PTGS2 and EGFR, have been previously shown to be up regulated in esophageal cancer. We therefore hypothesized that beta catenin expression may be altered in esophagus squamous cell cancer cells. Materials/Methods: Biopsy and surgical specimens were obtained from 30 unrelated esophageal cancer patients from this ethnic population in collaboration with the Gulestan University of Medical Sciences, Iran. Expression and cellular localization of beta catenin and E-cadherins in both normal and malignant cells were studied using immunecytochemistry techniques. Results: The most striking finding was the change in cellular localization of E-cadherin, which was highly expressed in the cell membrane of the normal epithelium but was completely absent in the cell membrane of the malignant cells. We observed similar changes in cellular expression of the beta catenin. While normal esophageal epithelium from the same affected individuals demonstrate strong membrane localization of beta catenin, malignant epithelial cells show markedly reduced to absent beta-catenin membrane localization. Such changes appear to be specific for esophageal squamous cell cancer as this was absent in some other malignant tumors such as in colon cancer (Figure 1). Conclusions: Our results demonstrate reduced cell membrane expression of beta catenin and E-cadherin in esophageal squamous cell cancer. Based on these findings, we hypothesize that reduced expression of beta catenin as well as E-cadherin may cause reduced cell-cell adhesion of the malignant cells and contribute to malignant behavior of the tumor cells. These results are very similar to previous findings in esophageal squamous cell cancer of East Asians and suggest that the esophageal squamous cell cancer in these two populations may have a common pathophysiology and/or genetic etiology. Further studies are required to understand the exact role of Wnt signaling in the pathogenesis of this type of squamous esophageal cancer of the esophagus