Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy.
OBJECTIVE
The aim of this study was to determine the prognostic value of expression of ATP binding cassette (ABC) transporter proteins and DNA repair gene proteins by immunohistochemically staining tumor biopsy specimens from patients with advanced non-small-cell lung cancer (NSCLC) being treated with platinum-based chemotherapy.


METHODS
Expression of ABC transporter proteins, including BCRP (breast cancer resistance protein) and MRP2 (multidrug resistance proteins 2), and the DNA-repair-related proteins, ERCC1 (excision repair cross-complementation group 1) and BRCA1 (breast cancer type 1 susceptibility protein) was assessed immunohistochemically in 156 tumor samples from untreated stage IV NSCLC patients. All of the patients had received platinum-based chemotherapy. Response to chemotherapy, progression-free survival (PFS), and overall survival were compared in relation to expression of each of the proteins and to clinicopathological factors.


RESULTS
High ERCC1 expression was associated with short survival (237 days vs. 453 days, log-rank P = 0.03), but not with response to chemotherapy or PFS. And high BCRP expression was associated with short survival (214 days vs. 412 days, log-rank P = 0.02) but not with response to chemotherapy or PFS. Multivariate analysis confirmed that negativity for the expression of BCRP tends to be an independent variable related to overall survival (P = 0.06).


CONCLUSIONS
This study examined ERCC1 and BCRP expression in biopsy specimens as candidates for predictors of the survival of patients with advanced NSCLC treated with platinum-based chemotherapy.
Ota
Shuji
S
Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Ishii
Genichiro
G
Goto
Koichi
K
Kubota
Kaoru
K
Kim
Young Hak
YH
Kojika
Masakazu
M
Murata
Yukinori
Y
Yamazaki
Manabu
M
Nishiwaki
Yutaka
Y
Eguchi
Kenji
K
Ochiai
Atsushi
A
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D002945:Cisplatin / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin