Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer.
BACKGROUND
ATP-binding cassette (ABC) transporter and DNA excision repair proteins play a pivotal role in the mechanisms of drug resistance. The aim of this study was to investigate the expression of ABC transporter and DNA excision repair proteins, and to elucidate the clinical significance of their expression in biopsy specimens from patients with small-cell lung cancer (SCLC).


METHODS
We investigated expression of the ABC transporter proteins, P-glycoprotein (Pgp), multidrug resistance associated-protein 1 (MRP1), MRP2, MRP3, and breast cancer resistance protein (BCRP), and the DNA excision repair proteins, excision repair cross-complementation group 1 (ERCC1) protein and breast cancer susceptibility gene 1 (BRCA1) protein, in tumor biopsy specimens obtained before chemotherapy from 130 SCLC patients who later received platinum-based combination chemotherapy, and investigated the relationship between their expression and both response and survival.


RESULTS
No significant associations were found between expression of Pgp, MRP1, MRP2, MRP3, ERCC1, or BRCA1 and either response or survival. However, there was a significant association between BCRP expression and both response (p=0.026) and progression-free survival (PFS; p=0.0103).


CONCLUSIONS
BCRP expression was significantly predictive of both response and progression-free survival (PFS) in SCLC patients receiving chemotherapy. These findings suggest that BCRP may play a crucial role in drug resistance mechanisms, and that it may serve as an ideal molecular target for the treatment of SCLC.
Kim
Young Hak
YH
Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Ishii
Genichiro
G
Goto
Koichi
K
Ota
Shuji
S
Kubota
Kaoru
K
Murata
Yukinori
Y
Mishima
Michiaki
M
Saijo
Nagahiro
N
Nishiwaki
Yutaka
Y
Ochiai
Atsushi
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004720:Endonucleases / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012189:Retrospective Studies; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D004720:Endonucleases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C116614:ABCG2 protein, human; C071447:ERCC1 protein, human