[Expression of proteins associated with multidrug resistance and resistance to chemotherapy in lung cancer].
OBJECTIVE
Membrane transporters are proteins that play a crucial role in resistance to chemotherapy. The aim of this study was to assess the influence of membrane transporter protein expression on chemotherapeutic response.


METHODS
One hundred and forty seven samples of tumor tissue were collected from 143 patients; 35 samples were obtained by bronchoscopy and 112 were surgical specimens. A total of 101 samples from 99 patients were adequate for study. Cryopreserved samples were subjected to immunohistochemical analysis to detect 3 proteins associated with multidrug resistance: P-glycoprotein (Pgp), multidrug-resistance-associated protein 1 (MRP1), and lung resistance protein (LRP).


RESULTS
In 16 cases none of the proteins were expressed. A single protein was expressed in 32 (3 Pgp, 11 MRP1, and 18 LRP); 2 in 34 cases (24 Pgp and LRP; 5 MRP1 and Pgp; 5 MRP1 and LRP); and all 3 in 17 cases. No significant relationship was found between age and the expression of Pgp (P=.74), MRP1 (P=.95), or LRP (P=.26). Nor were there significant differences in number (P=.72) or type of coexpressed proteins (P=.39) by sex, by tumor stage (number, P=.55; type, P=.21), or by tumor grade (number, P=.59; type, P=.51). There was a highly significant trend toward coexpression of Pgp and LRP (P< .01) but not of Pgp and MRP1 (P=.18) or MRP1 and LRP (P=.26). MRP1 was expressed less often in adenocarcinoma. LRP was expressed less often in squamous cell carcinoma than in adenocarcinoma and undifferentiated large cell carcinoma. Coexpression of Pgp, MRP1, and LRP was observed most often in squamous cell carcinoma.


CONCLUSIONS
Proteins associated with multidrug resistance are commonly expressed in lung cancer. Of the 3 proteins studied, LRP was the one most often found. Coexpression of more than 1 of the proteins was found in a considerable percentage of patients. Pgp was mainly found to be coexpressed with LRP. Pgp expression and the number of coexpressed proteins seemed to have a negative impact on response to chemotherapy.
Paredes Lario
Alfredo
A
Servicio de Oncología, Hospital Donostia, San Sebastián, Guipúzcoa, España.
Blanco García
Carlos
C
Echenique Elizondo
Miguel
M
Lobo
Carmen
C
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis*; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C421109:multidrug resistance-associated protein 1