title: Cyclooxygenase-2 and Hypoxia-Inducible Factor-1alpha protein expression is related to inflammation, and up-regulated since the early steps of colorectal carcinogenesis.
abstract: Chronic mucosal inflammation is considered a risk factor for colorectal cancer. Neutrophils are a major source of oxidants, whereas cyclooxygenase 2 (COX-2) and Hypoxia Inducible Factor-1alpha (HIF-1alpha) protein expression levels are increased in inflammatory and malignant lesions. The main purpose of the present study was to evaluate myeloperoxidase (MPO) positive cell infiltration, COX-2 and HIF-1alpha protein expression in colorectal carcinogenesis, especially in its early phases, using immunohistochemistry and immunofluorescence confocal microscopy techniques. MPO, COX-2 and HIF-1alpha proteins were expressed at higher rates in the normal colorectal mucosa of patients with inflammatory bowel diseases and colorectal tumours than in patients with normal colonoscopy. A gradual increase in COX-2 and HIF-1alpha protein expression was observed in dysplastic aberrant crypt foci, adenomas and carcinomas, showing a strong relation to dysplasia. In conclusion, the present study supports the hypothesis of a key role of inflammation in malignant transformation of colorectal mucosa. The evaluation of some early markers related to inflammation in the mucosa of the large bowel may serve as potential tool for prognosis and therapeutic strategies.
authors.affiliation: Department of Internal Medicine, University of Modena and Reggio Emilia, Via Del Pozzo 71, 41100 Modena, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mariani
authors.forename: Paola
authors.initials: P
authors.lastname: Sena
authors.forename: Laura
authors.initials: L
authors.lastname: Marzona
authors.forename: Massimo
authors.initials: M
authors.lastname: Riccio
authors.forename: Rita
authors.initials: R
authors.lastname: Fano
authors.forename: Paola
authors.initials: P
authors.lastname: Manni
authors.forename: Carmela Di
authors.initials: CD
authors.lastname: Gregorio
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pezzi
authors.forename: Maurizio Ponz de
authors.initials: MP
authors.lastname: Leon
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Monni
authors.forename: Anto De
authors.initials: AD
authors.lastname: Pol
authors.forename: Luca
authors.initials: L
authors.lastname: Roncucci
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009195:Peroxidase; D051546:Cyclooxygenase 2