Vascular endothelial growth factor and cyclooxygenase-2 are overexpressed in ileal pouch-anal anastomosis.
OBJECTIVE
Pathophysiology of pouchitis after ileal pouch-anal anastomosis is controversial because of the potential for development of carcinoma. Cyclooxygenase-2-derived prostaglandins may be involved in the inflammatory process and play a role in the pathogenesis of colon cancer. Vascular endothelial growth factor plays a major role in neoangiogenesis and is overexpressed in a number of gastrointestinal malignancies. The goal of this study was to evaluate the expression of cyclooxygenase-2 and vascular endothelial growth factor and to assess neoangiogenesis and epithelial cell proliferation in patients with ileal pouch-anal anastomosis.


METHODS
Endoscopic biopsies were obtained from 15 patients with ileal pouch-anal anastomosis without pouchitis (10 biopsies from the ileal pouch and 10 from ileal nonpouch mucosa) and from 15 subjects with irritable bowel syndrome (10 biopsies from normal-appearing ileum and rectum). Cyclooxygenase-1, cyclooxygenase-2, and vascular endothelial growth factor messenger ribonucleic acid expression was determined by reverse transcriptase polymerase chain reaction. Cyclooxygenase-2 and vascular endothelial growth factor protein expression was evaluated by Western blot. Cyclooxygenase-2, vascular endothelial growth factor, CD34 (neoangiogenesis marker), and Ki67 (proliferation marker) mucosal localizations were evaluated by immunohistochemistry.


RESULTS
Expression of cyclooxygenase-2 and vascular endothelial growth factor was increased in ileal pouch mucosa compared with ileal nonpouch mucosa, normal ileum, and rectum. Cyclooxygenase-2 and vascular endothelial growth factor immunostaining in ileal pouch mucosa was more intense in the crypt area than in the surface epithelium compared with ileal nonpouch mucosa. CD34 (neoangiogenesis marker) and Ki67 (proliferation marker) expression was increased in ileal pouch mucosa.


CONCLUSIONS
Cyclooxygenase-2 and vascular endothelial growth factor are overexpressed in the ileal pouch mucosa. This is associated with increased proliferative activity and neoangiogenesis. Cyclooxygenase-2 and vascular endothelial growth factor overexpression might play a role in the pathogenesis of pouchitis.
Romano
Marco
M
Dipartimento di Internistica Clinica e Sperimentale-Cattedra di Gastroenterologia, Seconda Università di Napoli, c/o II Policlinico, Edificio 3, Via Pansini 5, Napoli, 80131, Italy. marco.romano@unina2.it
Cuomo
Antonio
A
Tuccillo
Concetta
C
Salerno
Raffaele
R
Rocco
Alba
A
Staibano
Stefania
S
Mascolo
Massimo
M
Sciaudone
Guido
G
Mucherino
Caterina
C
Giuliani
Antonio
A
Riegler
Gabriele
G
Nardone
Gerardo
G
Del Vecchio Blanco
Camillo
C
Selvaggi
Francesco
F
D000328:Adult; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000601:surgery*; D039021:Colonic Pouches; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016737:Proctocolectomy, Restorative; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2