Home » AGEB Journal » Issues » Volume 62 » Fasc.4 - Case series

Volume 62 - 1999 - Fasc.4 - Case series

Endoscopic therapy of Barrett's oesophagus : critical review

Barrett's oesophagus is known as one of the most important risk factor of oesophageal adenocarcinoma. Because of the increasing incidence of these latter, many endoscopic methods such as argon plasma coagulation, photodynamic therapy or endoscopic mucosal resection are now in evaluation in order to eradicate Barrett's oesophagus or to treat dysplasia and early cancers arising from this metaplasia. The aim of this paper is to comment these techniques and discuss their usefulness.


The role of the E-cadherin - catenin complex in gastrointestinal cancer

Cancer is a genetic disease. The unstable genome of cancer cells causes tttmour progression through multiple alterations in suppressor and promoter genes, leading to loss of homeostatic and gain of oncogenic functions. Invasion is the critical step in the acquisition of malignancy. It implicates a continuous molecular conversation of the cancer cells with other cells and with the extraceflular matrix in which adhesion molecules are crucial. One of these, E-cadherin, is discussed in the present review. E-cadherin is a transmembrane glycoprotein that forms a complex with cytoplasmic proteins, termed catenins because they link E-cadherin to the actin cytoskeleton. Ecadherin/catenin-mediated intercellular adhesion and communication is mainly homophylic homotypic. There is compelling evidence from experiments in vitro as well as in vivo to accept that the E-cadherin/ catenin complex acts as an invasion suppressor. The mechanism of this action is not only through cell-cell adhesion but also tbrou2h transduction of signals to the cell's motility system. In the replication error positive human colon cancer cell line HCT-8, the cEE-catenin gene CTNNAI is an invasion suppressor gene. Here, the transition from the non-invasive to the invasive state was prevented by introduction into the unstable non-invasive cells of either an extra CTNNA] or a wild type hUSH6 mismatcb repair gene. 0-catenin also participates at a complex which comprises the adenomatous polyposis cancer protein APC. In colorectal cancer, mutation of either APC or P-catenin is oneogenic. Downregulation of the E-cadherin/catenin complex may occur in several ways amongst which are gene mutations, methylation of 5CpG dinucleotides within the promotor region of E-cadherin, tyrosine phosphorylation of 0-catenin, cell surface expression of proteoglycans sterically hindering E-cadherin and proteolytic release of fragments from the extracellular part of E-cadherin. Upregulation of the E-cadheirin/cateniii complex has been realized with a series of agents, some of which can be used therapeutically. In most human gastrointestinal cancers the E-cadherin/catenin or related complexes are disturbed and this underscores their pivotal role in the progression of these tumours. Mutations of the E-cadherin gene, including germline mutations, occur in diffuse gastric carcinoma, CpG methylation around the promotor region of E-cadherin in hepatocellular carcinomas and mutations of the APC tumour suppressor gene or in the 0-catenin oncogene in most colorectal cancers. The literature agrees about the disturbance of immunohistochemical patterns of E-cadherin and catenin expression in gastrointestinal cancers. Conflicting opinions dO. however, exist about the prognostic value of such immunohistochemical aberrations. We doubt that immunohistochemistry of E-cadherin or catenins add prognostic value to the already used histological grading systems. In our opinion the major benefit from understanding of the E-cadherin/catenin-mediated pathways of invasion will be the development of new anti-invasive treatment strategies.


Haemochromatosis and HFE gene

The discovery of the HFE gene has improved classification and diagnosis of iron overload. Most patients with a phenotypic diagnosis of haemochromatosis are bomozygote for the C282Y mutation. Among those with other genotypes, only compound heterozygotes, who present the C282Y mutation on one chromosome and the H63D on the other, may present with haemochromatosis, but with a low penetrance and a mild expression. Other patients usually present with another cause of iron overload, such as insulin resistance, alcoholic liver disease or liver cirrhosis. The practical management of haemochromatosis has been greatly modified, since liver biopsy is no more necessary for diagnosis in C282Y homozygotes, and is only needed for exclusion of cirrhosis. Family screening has also greatly benefited from genotyping. (Acta gastroelnterol. belg., 1999, 62, 403-409).