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Vol. 43. Issue 9.
Pages 479-484 (January 2007)
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Vol. 43. Issue 9.
Pages 479-484 (January 2007)
Original Articles
DOI: 10.1016/S1579-2129(07)60111-6
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Expression of Proteins Associated With Multidrug Resistance to Chemotherapy in Lung Cancer
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Alfredo Paredes Larioa, Carlos Blanco Garcíab, Miguel Echenique Elizondoc,
Corresponding author
gepecelm@sc.ehu.es

Correspondence: Dr. M. Echenique Elizondo. Facultad de Medicina. UD San Sebastián. Universidad del País Vasco. P.° Dr. Begiristain, 105. 20014 San Sebastián. Guipúzcoa. España
, Carmen Lobod
a Servicio de Oncología, Hospital Donostia, San Sebastián, Guipúzcoa, Spain
b Servicio de Radioterapia, Hospital Donostia, San Sebastián, Guipúzcoa, Spain
c Departamento de Cirugía, Facultad de Medicina, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain
d Servicio de Patología, Hospital Donostia, San Sebastián, Guipúzcoa, Spain
Article information
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.

Material and 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), multidrugresistance–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.

Key words:
Multidrug-resistance proteins
Lung cancer
Chemotherapy
Objetivo

Las proteínas transportadoras de membrana desempeñan un papel esencial en la resistencia a la quimioterapia. El objetivo del estudio ha sido intentar valorar la influencia de su expresión en la respuesta a la quimioterapia.

Material y métodos

Se recogieron 147 muestras tumorales procedentes de 143 pacientes. De ellas, 35 eran broncoscó-picas y 112 quirúrgicas. Resultaron válidas para el estudio 101, correspondientes a 99 pacientes. Las muestras tumorales criocongeladas se sometieron a análisis inmunohistoquímico para la detección de las 3 proteínas relacionadas con resistencia a múltiples fármacos (MDR-proteínas): Pgp, Mrp1 y Lrp.

Resultados

No expresaban ninguna proteína 16 casos. Se encontró expresión de una sola proteína en 32 casos (3 Pgp, 11 Mrp1 y 18 Lrp); de 2 proteínas en 34 casos (24 Pgp + Lrp; 5 Mrp1 + Pgp; 5 Mrp1 + Lrp), y de las 3 proteínas en 17. No encontramos relación significativa entre la edad y la expresión de Pgp (p = 0,74), Mrp1 (p = 0,95) o Lrp (p = 0,26). No observamos diferencias significativas entre sexos por el número (p = 0,72) ni por el tipo (p = 0,39) de proteínas expresadas de forma simultánea. Tampoco detectamos diferencias significativas entre estadios tumorales por el número (p = 0,55) ni por el tipo (p = 0,21) de MDR-proteínas. No encontramos diferencias significativas entre los diferentes grados histológicos ni por el número (p = 0,59) ni por el tipo (p = 0,51) de MDR-proteínas expresadas simultáneamente. La tendencia de Pgp y Lrp a expresarse asociadas resultó muy significativa (p < 0,01), pero no fue así en el caso de la asociación de Pgp y Mrp1 (p = 0,18) o Mrp1 y Lrp (p = 0,26). Los adenocarcinomas expresaron menos la Mrp1. Los carcinomas escamosos expresaron menos Lrp que los adenocarcinomas y carcinomas indiferenciados de células grandes. Los carcinomas escamosos fueron los que con más frecuencia expresaron Pgp, Mrp1 y Lrp de forma simultánea.

Conclusiones

El cáncer de pulmón expresa con frecuencia MDR-proteínas. De las 3 estudiadas (Pgp, Mrp1 y Lrp), la más frecuentemente observada fue Lrp. En una proporción importante de pacientes se halló expresión simultánea de más de una MDR-proteína. Pgp se expresó fundamentalmente asociada a Lrp. La expresión de Pgp y el número de proteínas expresadas simultáneamente parecieron afectar de forma negativa a la respuesta a la quimioterapia.

Palabras clave:
MDR-proteínas
Cáncer de pulmón
Quimioterapia
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Copyright © 2007. Sociedad Española de Neumología y Cirugía Torácica (SEPAR)
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