Multidrug resistance gene (MDR-1) expression in the colonic mucosa of patients with refractory ulcerative colitis.
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.


OBJECTIVE
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.
Sambuelli
Alicia María
AM
IBD Section, Clinical Service Dr C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina. asambu@fibertel.com.ar
Negreira
Silvia Mónica
SM
Gil
Aníbal Héctor
AH
Huernos
Sergio Pablo
SP
Goncalves
Silvina
S
Toro
Martín Ariel
MA
Kogan
Zulema
Z
Cabanne
Ana
A
Camarero
Sandra
S
Bai
Julio César
JC
Lazarowski
Alberto Jorge
AJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000737:chemistry; D039021:Colonic Pouches; D004847:Epithelial Cells / Q000737:chemistry; D015870:Gene Expression; D019450:Genes, MDR; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1