Adenocarcinoma Of Oesophagus Junction And Cardia: Similar Response To Neoadjuvant Therapy.

Introduction: Selenium, which is discussed as a potential micronutrient in the prevention of colorectal cancer, is an essential component of Selenoprotein P (SeP) and the gastrointestinal glutathione peroxidase (GI-GPX).Glutathione peroxidases reduce lipidic and nonlipidic hydroperoxides, using reduced glutathione as cosubstrate.The gastrointestinal isoenzyme GI-GPX plays an important role in the antioxidant defense of the human digestive tract.SeP, a heavily glycosylated, secreted protein of still unknown function, is suggested to be involved in redox-regulation.Therefore, we studied the expression of SeP and GI-GPX mRNA in colorectal adenomas as well as in the normal surrounding mucosa.Methods: Biopsies were obtained from colorectal adenomas and the macroscopically and histologically normal adjacent mucosa.Total RNA was extracted from the tissue samples, and the expression of SeP and GI-GPX was determined by Northern blot analysis.As a reference, pooled tissue samples from macroscopically and histologically normal mucosa were obtained.Results: Abundant mRNA signals of GI-GPX and SeP in the normal colon mucosa were previously described by our group.In the biopsy samples obtained from adenomas, GI-GPX mRNA levels were increased, whereas only weak signals were detected in the surrounding mucosa.In contrast, SeP mRNA expression in the adenoma specimens was markedly reduced, as compared to high levels in normal adjacent tissue.Discussion: According to animal models and epidemiological data, low selenium levels may facilitate the development of colorectal cancer.As a potential mechanism, selenocysteine-containing proteins could be involved in tumor inhibition by protection against oxidative injury.The markedly increased expression of GI-GPX found in our study may support this hypothesis.Because of the still unknown biological function of SeP, the very low expression of SeP mRNA in adenomas is difficult to explain.The downregulated gene expression of SeP in colorectal adenomas as compared to the adjacent mucosa indicates a connection with different stages of cell differentiation and proliferation.