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

Filipits, Martin; Haddad, Vincent; Schmid, Katharina; Huynh, Anh; Dunant, Ariane; André, Fabrice; Brambilla, Élisabeth; Stahel, Rolf A.; Pignon, Jean-Pierre; Soria, Jean‐Charles; Popper, Helmut; Chevalier, Thierry Le; Pirker, Robert

doi:10.1158/1078-0432.ccr-06-2446

Cited by 69 publications

(41 citation statements)

References 20 publications

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“…Filipits et al (18) found that NSCLC patients suitable for surgery had a positive MRP1 expression rate of 47% and a positive MRP2 expression of 40%. The overall survival rates of NSCLC patients with a positive MRP2 expression were markedly shorter compared with those of patients with a negative MRP2 expression (P=0.007), suggesting that MRP2 protein expression may be an indicator of poor prognosis of NSCLC patients suitable for surgery.…”

Section: Surgerymentioning

confidence: 99%

Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients

Wang

Xiao

et al. 2013

Molecular and Clinical Oncology

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Abstract. The incidence of lung cancer is one of the leading causes of mortality. This study aimed to investigate the prognostic and predictive importance of p53, c-erbB2 and multidrug resistance proteins (MRP) expression and its correlation with clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). Expression of p53, c-erbB2 and MRP proteins in 152 tumor samples from resected primary NSCLCs was detected by immunohistochemical staining. The correlation of proteins, survival and clinicopathological characteristics was investigated in 152 patients undergoing potentially curative surgery. The positive rates of p53, c-erbB2 and MRP expression were 53.9 (82/152), 44.1 (67/152) and 43.4% (66/152), respectively. Overall survival rates of patients were markedly correlated with the overexpression of p53, c-erbB2 and MRP proteins. One, 2-and 3-year survival rates of patients exhibiting a positive expression of these proteins were 72.6, 54.8 and 32.2%, respectively. These rates were lower compared with those of patients with a negative expression of these proteins (92.1, 78.5 and 63.4%) (P=0.02, 0.01 or 0.00, respectively). Results of Cox's regression analysis showed that c-erbB2 expression and cell differentiation were independent prognostic factors in patients with NSCLC. These findings suggest that the positive expression of p53, c-erbB2 and MRP proteins is correlated with the survival rates of NSCLC patients. Detection of positive p53, c-erbB2 and MRP expression may be a useful predictive indicator of prognosis. Positive c-erbB2 expression is an independent prognostic factor, with a potential to be used as a predictive indicator of chemotherapy efficacy in NSCLC patients.

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Section: Surgerymentioning

confidence: 99%

Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients

Wang

Xiao

et al. 2013

Molecular and Clinical Oncology

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“…Multicenter clinical trails with larger sample size, such as the International Adjuvant Lung Cancer Trial biologic Program (IALT-bio) and the Lung Adjuvant Cisplatin Evaluation biologic Program (LACE-Bio) (25)(26)(27), should be conducted for the application of ERCC1 in clinic. Nevertheless, studies on biomarkers like ERCC1 provides an onset for overcoming drug resistance and tailoring chemotherapy in NSCLC treatment.…”

Section: Introductionmentioning

confidence: 99%

Excision repair cross complementation group 1 is a chemotherapy-tolerating gene in cisplatin-based treatment for non-small cell lung cancer

Wang

Pan

Liu

et al. 2014

International Journal of Oncology

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Abstract. This study aimed to evaluate the biological functions of excision repair cross complementation goup 1 (ERCC1) in cell proliferation, cell cycle, invasion and cisplatin response of non-small cell lung cancer (NSCLC) cells. Firstly, ERCC1 gene was successfully transfected into H1299 cells by gene cloning and transfection techniques. Then, cell proliferation was determined with the cell growth curve and colony-forming assays. Flow cytometry (FCM) was employed to investigate the cell cycle distribution. The ability of cell invasion was estimated by means of Matrigel invasion assays. Response of NSCLC cells to cisplatin was detected utilizing MTT assays, and the intracellular drug concentrations were determined by the high performance liquid chromatography (HPLC) analysis. Expression of the two cell membrane proteins, P-glycoprotein (P-gp) and multidrug resistanceassociated protein (MRP), was also evaluated utilizing FCM technique. By contrast, ERCC1 expression in the NSCLC A549 cells was silenced by small interfering RNA (siRNA) through RNAi technique. In addition, the cytotoxic effect of cisplatin on A549 cells was detected by MTT assays. In the present study, the results demonstrated that ERCC1 had no effect on cell proliferation, cell cycle and the ability of invasion, but showed significant impact on cisplatin response of the NSCLC H1299 cells. Furthermore, siRNA-induced suppression of ERCC1 evidently enhanced sensitivity to cisplatin of NSCLC A549 cells. Therefore, it is confirmed that ERCC1 is a chemotherapy-tolerating gene and a promising predictor in tailoring chemotherapy of NSCLC.

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“…The expression of ABCC1 has been described in NSCLC (19). No positivity was seen for ABCC1 in the tumor presenting the EGFR mutation despite being present in four other adenocarcinomas not bearing the mutation.…”

Section: Discussionmentioning

confidence: 96%

Expression of ABC transporters, p53, Bax, Bcl-2 in an archival sample of non-small cell lung cancer bearing a deletion in the EGFR gene

Amoêdo

Castelo-Branco²,

Paschoal³

et al. 2009

Int J Mol Med

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Abstract. EGFR mutations have been correlated to responsiveness to treatment with tyrosine kinase inhibitors. These drugs are themselves substrates for ABC transporters. In the present work we describe the immunohistochemical profile of an archival sample from a male Brazilian patient with no Asian ancestry and never smoker, diagnosed with non-small cell lung cancer. This tumor was found to contain an in-frame hemi-or homozygous deletion, E746-A750 in exon 19 of the EGFR gene. Immunohistochemistry revealed a relatively weak staining for the ABC transporter subfamily ABCC1 and strongly for ABCB1. The cytoplasm stained positively for Bax and the nucleus stained for p53, but was negative for Bcl-2. Antibody against acetylated lysine revealed staining in both, cytoplasm and nucleus of tumor cells in contrast to normal cells which were essentially negative. The overall immunohistochemistry pattern obtained for this sample indicates that the del E746-A750 mutation may have downregulated the expression of ABCC1. The results also suggest that the NSCLC analyzed displayed a transcriptionally active chromatin as judged by the results obtained with the antiacetylated lysine antibody.

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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

Cited by 69 publications

References 20 publications

Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients

Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients

Excision repair cross complementation group 1 is a chemotherapy-tolerating gene in cisplatin-based treatment for non-small cell lung cancer

Expression of ABC transporters, p53, Bax, Bcl-2 in an archival sample of non-small cell lung cancer bearing a deletion in the EGFR gene

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