J Cancer 2015; 6(11):1079-1086. doi:10.7150/jca.12606 This issue Cite

Research Paper

ABC-Transporter Expression Does Not Correlate with Response to Irinotecan in Patients with Metastatic Colorectal Cancer

K. Trumpi1, B.L. Emmink1, A.M. Prins1, M.G.H. van Oijen2,4, P.J. van Diest3, C.J.A. Punt4, M. Koopman2, O. Kranenburg1, I.H.M. Borel Rinkes1✉

1. Department of Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
2. Department of Medical Oncology, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
3. Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
4. Department of Medical Oncology, Academic Medical Centre, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands

Citation:
Trumpi K, Emmink BL, Prins AM, van Oijen MGH, van Diest PJ, Punt CJA, Koopman M, Kranenburg O, Rinkes IHMB. ABC-Transporter Expression Does Not Correlate with Response to Irinotecan in Patients with Metastatic Colorectal Cancer. J Cancer 2015; 6(11):1079-1086. doi:10.7150/jca.12606. https://www.jcancer.org/v06p1079.htm
Other styles

File import instruction

Abstract

Background: Active efflux of irinotecan by ATP-binding cassette (ABC)-transporters, in particular ABCB1 and ABCG2, is a well-established drug resistance mechanism in vitro and in pre-clinical mouse models, but its relevance in colorectal cancer (CRC) patients is unknown. Therefore, we assessed the association between ABC-transporter expression and tumour response to irinotecan in patients with metastatic CRC.

Methods: Tissue microarrays of a large cohort of metastatic CRC patients treated with irinotecan in a prospective study (CAIRO study; n=566) were analysed for expression of ABCB1 and ABCG2 by immunohistochemistry. Kaplan-Meier and Cox proportional hazard regression analyses were performed to assess the association of ABC transporter expression with irinotecan response. Gene expression profiles of 17 paired tumours were used to assess the concordance of ABCB1/ABCG2 expression in primary CRC and corresponding metastases.

Results: The response to irinotecan was not significantly different between primary tumours with positive versus negative expression of ABCB1 (5.8 vs 5.7 months, p=0.696) or ABCG2 (5.7 vs 6.1 months, p=0.811). Multivariate analysis showed neither ABCB1 nor ABCG2 were independent predictors for progression free survival. There was a mediocre to poor concordance between ABC-transporter expression in paired tumours.

Conclusion: In metastatic CRC, ABC-transporter expression in the primary tumour does not predict irinotecan response.

Keywords: metastatic colorectal cancer, ABC-transporters, ABCB1, ABCG2, Irinotecan, chemotherapy, CAIRO


Citation styles

APA
Trumpi, K., Emmink, B.L., Prins, A.M., van Oijen, M.G.H., van Diest, P.J., Punt, C.J.A., Koopman, M., Kranenburg, O., Rinkes, I.H.M.B. (2015). ABC-Transporter Expression Does Not Correlate with Response to Irinotecan in Patients with Metastatic Colorectal Cancer. Journal of Cancer, 6(11), 1079-1086. https://doi.org/10.7150/jca.12606.

ACS
Trumpi, K.; Emmink, B.L.; Prins, A.M.; van Oijen, M.G.H.; van Diest, P.J.; Punt, C.J.A.; Koopman, M.; Kranenburg, O.; Rinkes, I.H.M.B. ABC-Transporter Expression Does Not Correlate with Response to Irinotecan in Patients with Metastatic Colorectal Cancer. J. Cancer 2015, 6 (11), 1079-1086. DOI: 10.7150/jca.12606.

NLM
Trumpi K, Emmink BL, Prins AM, van Oijen MGH, van Diest PJ, Punt CJA, Koopman M, Kranenburg O, Rinkes IHMB. ABC-Transporter Expression Does Not Correlate with Response to Irinotecan in Patients with Metastatic Colorectal Cancer. J Cancer 2015; 6(11):1079-1086. doi:10.7150/jca.12606. https://www.jcancer.org/v06p1079.htm

CSE
Trumpi K, Emmink BL, Prins AM, van Oijen MGH, van Diest PJ, Punt CJA, Koopman M, Kranenburg O, Rinkes IHMB. 2015. ABC-Transporter Expression Does Not Correlate with Response to Irinotecan in Patients with Metastatic Colorectal Cancer. J Cancer. 6(11):1079-1086.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Popup Image