Multidrug resistance gene (MDR-1) expression in the colonic mucosa of patients with refractory ulcerative colitis
Acta gastroenterol. latinoam
; 36(1): 23-32, mar. 2006. ilus, graf, tab
Article
in En
| BINACIS
| ID: bin-123356
Responsible library:
BR1.1
ABSTRACT
BACKGROUND:
P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial.AIM:
to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients.METHODS:
P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas).RESULTS:
Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical 9/11 cases, cytoplasmic 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC.CONCLUSIONS:
These results suggest a critical role of P-gp overexpression in steroid-refractory UC.(AU)
Full text:
1
Collection:
06-national
/
AR
Database:
BINACIS
Main subject:
Colitis, Ulcerative
/
ATP Binding Cassette Transporter, Subfamily B, Member 1
/
Genes, MDR
Limits:
Humans
Language:
En
Journal:
Acta gastroenterol. latinoam
Year:
2006
Document type:
Article
/
Congress and conference
Country of publication:
Argentina