Multidrug resistance proteins do not predict benefit of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer: International Adjuvant Lung Cancer Trial Biologic Program.
OBJECTIVE
The purpose of our study was to determine whether multidrug resistance proteins (MRP) are of prognostic and/or predictive value in patients who were enrolled into the International Adjuvant Lung Cancer Trial (IALT).


METHODS
Expression of MRP1 and MRP2 was immunohistochemically assessed in tumor specimens obtained from 782 IALT patients. Prognostic and predictive analyses were based on Cox models adjusted for clinical and pathologic variables.


RESULTS
MRP1 expression was considered positive in 364 (47%) patients and MRP2 expression in 313 (40%) patients. MRP2-positive patients had a significantly shorter overall survival than MRP2-negative patients in the total patient population [adjusted hazard ratio for death, 1.37; 95% confidence interval (95% CI), 1.09-1.72; P = 0.007]. There was no significant association between MRP1 expression and overall survival. Neither MRP1 nor MRP2 predicted response to adjuvant cisplatin-based chemotherapy.


CONCLUSIONS
MRP2 expression is an independent prognostic factor in patients with completely resected non-small cell lung cancer but neither MRP1 nor MRP2 was of predictive value in patients enrolled into the IALT.
Filipits
Martin
M
Department of Medicine I, Medical University of Vienna, Vienna, Austria. martin.filipits@meduniwien.ac.at
Haddad
Vincent
V
Schmid
Katharina
K
Huynh
Anh
A
Dunant
Ariane
A
André
Fabrice
F
Brambilla
Elisabeth
E
Stahel
Rolf
R
Pignon
Jean-Pierre
JP
Soria
Jean-Charles
JC
Popper
Helmut H
HH
Le Chevalier
Thierry
T
Pirker
Robert
R
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000601:surgery*; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D011379:Prognosis; D012189:Retrospective Studies
D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human; C421109:multidrug resistance-associated protein 1