Myeloperoxidase-positive cell infiltration in colorectal carcinogenesis as indicator of colorectal cancer risk.
Colorectal mucosa is targeted by toxic agents, which can initiate or promote colon cancer. The mechanism of damage might be a focal irritation with loss of normal epithelial cell barrier function. Genetic alterations in tumors may also affect host inflammatory response. The aim of this study was to define the extent of inflammation in colorectal mucosa, along colorectal carcinogenesis, and in microsatellite stable and unstable colorectal carcinomas. We collected 103 samples of normal colorectal mucosa from 65 patients (35 with colorectal cancer or adenoma, 8 with inflammatory bowel diseases, and 22 controls with normal colonoscopy). We also examined 24 aberrant crypt foci, 14 hyperplastic polyps, 16 adenomas, and 67 samples of colorectal carcinoma. Immunohistochemistry was used to count myeloperoxidase (MPO)-positive cells (neutrophils and monocytes) in x100 optical fields under a light microscope. Patients with colorectal tumors had a higher mean number of MPO-positive cells in normal mucosa than controls (mean +/- SD, 2.7 +/- 2.0 versus 1.4 +/- 1.4; P = 0.017). MPO-positive cell number was tightly linked to dysplasia in aberrant crypt foci and adenomas, and it was higher in carcinomas microsatellite unstable than those microsatellite stable (21.6 +/- 15.5 versus 11.9 +/- 8.0; P < 0.01). MPO immunohistochemistry is a simple and reliable technique for the quantification of inflammation in colorectal mucosa., and it may be a potential marker of colorectal cancer risk. Microsatellite instability seems to influence host immune responses to colorectal carcinoma. These observations strongly support a key role of inflammation in colorectal carcinogenesis.
Roncucci
Luca
L
Department of Internal Medicine, University of Modena and Reggio Emilia, Policlinico, Modena, Italy. roncucci@unimo.it
Mora
Erika
E
Mariani
Francesco
F
Bursi
Serena
S
Pezzi
Annalisa
A
Rossi
Giuseppina
G
Pedroni
Monica
M
Luppi
Davide
D
Santoro
Luisa
L
Monni
Sebastiano
S
Manenti
Antonio
A
Bertani
Angela
A
Merighi
Alberto
A
Benatti
Piero
P
Di Gregorio
Carmela
C
de Leon
Ponz Maurizio
PM