Clinical significance of multi-drug resistance associated protein and P-glycoprotein in patients with bladder cancer.
OBJECTIVE
The clinical significance of multi-drug resistant proteins, such as multi-drug resistance associated protein and P-glycoprotein, in terms of prognostic value was determined in patients with bladder cancer.


METHODS
The expression of multi-drug resistance associated protein and P-glycoprotein was investigated immunohistochemically before and after chemotherapy. The relationship between expression of these multi-drug resistant proteins and clinical outcome assessed by tumor recurrence rate, cystectomy rate and 5-year survival rate was also investigated in 33 patients with bladder cancer.


RESULTS
Before chemotherapy multi-drug resistance associated protein expression was observed in 1 of 28 patients (4%) while P-glycoprotein expression was observed in 22 of 33 (67%). Multi-drug resistance associated protein induction by chemotherapy was observed in 6 of 28 patients (21%), whereas P-glycoprotein induction was noted in 4 (14%). Multi-drug resistance associated protein in this disease is induced more frequently by high dose (more than 300 mg.) than low dose (less than 300 mg.) anthracyclines (p < 0.01). Immunohistochemical analysis also revealed co-expression of multi-drug resistance associated protein and P-glycoprotein in 5 of 28 patients (18%) after chemotherapy. However, there was no significant correlation between positive P-glycoprotein expression before chemotherapy and clinical outcome.


CONCLUSIONS
Multi-drug resistance associated protein as well as P-glycoprotein mediated multi-drug resistance may be induced after chemotherapy for bladder tumors. However, the presence of P-glycoprotein before chemotherapy does not predict clinical outcome in patients with bladder cancer.
Nakagawa
M
M
Department of Urology, Oita Medical University, Japan.
Emoto
A
A
Nasu
N
N
Hanada
T
T
Kuwano
M
M
Cole
S P
SP
Nomura
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000096:biosynthesis*; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins