ABC-transporter expression does not correlate with response to irinotecan in patients with metastatic colorectal cancer

K. Trumpi, B. L. Emmink, A. M. Prins, M. G H van Oijen, P. J. van Diest, C. J A Punt, M. Koopman, O. Kranenburg, I. H M Borel Rinkes

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1079-1086
Number of pages8
JournalJournal of Cancer
Volume6
Issue number11
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

irinotecan
ATP-Binding Cassette Transporters
Colorectal Neoplasms
Neoplasms
Transcriptome
Drug Resistance
Disease-Free Survival
Multivariate Analysis
Immunohistochemistry
Regression Analysis

Keywords

  • ABC-transporters
  • ABCB1
  • ABCG2
  • CAIRO
  • Chemotherapy
  • Irinotecan
  • Metastatic colorectal cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Trumpi, K., Emmink, B. L., Prins, A. M., van Oijen, M. G. H., van Diest, P. J., Punt, C. J. A., ... Borel Rinkes, I. H. M. (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

ABC-transporter expression does not correlate with response to irinotecan in patients with metastatic colorectal cancer. / 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.; Borel Rinkes, I. H M.

In: Journal of Cancer, Vol. 6, No. 11, 2015, p. 1079-1086.

Research output: Contribution to journalArticle

Trumpi, K, Emmink, BL, Prins, AM, van Oijen, MGH, van Diest, PJ, Punt, CJA, Koopman, M, Kranenburg, O & Borel Rinkes, IHM 2015, 'ABC-transporter expression does not correlate with response to irinotecan in patients with metastatic colorectal cancer', Journal of Cancer, vol. 6, no. 11, pp. 1079-1086. https://doi.org/10.7150/jca.12606
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. ; Borel Rinkes, I. H M. / ABC-transporter expression does not correlate with response to irinotecan in patients with metastatic colorectal cancer. In: Journal of Cancer. 2015 ; Vol. 6, No. 11. pp. 1079-1086.
@article{0f64f3d71284444295f72835a351d322,
title = "ABC-transporter expression does not correlate with response to irinotecan in patients with metastatic colorectal cancer",
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 = "ABC-transporters, ABCB1, ABCG2, CAIRO, Chemotherapy, Irinotecan, Metastatic colorectal cancer",
author = "K. Trumpi and Emmink, {B. L.} and Prins, {A. M.} and {van Oijen}, {M. G H} and {van Diest}, {P. J.} and Punt, {C. J A} and M. Koopman and O. Kranenburg and {Borel Rinkes}, {I. H M}",
year = "2015",
doi = "10.7150/jca.12606",
language = "English (US)",
volume = "6",
pages = "1079--1086",
journal = "Journal of Cancer",
issn = "1837-9664",
publisher = "Ivyspring International Publisher",
number = "11",

}

TY - JOUR

T1 - ABC-transporter expression does not correlate with response to irinotecan in patients with metastatic colorectal cancer

AU - Trumpi, K.

AU - Emmink, B. L.

AU - Prins, A. M.

AU - van Oijen, M. G H

AU - van Diest, P. J.

AU - Punt, C. J A

AU - Koopman, M.

AU - Kranenburg, O.

AU - Borel Rinkes, I. H M

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - ABC-transporters

KW - ABCB1

KW - ABCG2

KW - CAIRO

KW - Chemotherapy

KW - Irinotecan

KW - Metastatic colorectal cancer

UR - http://www.scopus.com/inward/record.url?scp=84947733560&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947733560&partnerID=8YFLogxK

U2 - 10.7150/jca.12606

DO - 10.7150/jca.12606

M3 - Article

VL - 6

SP - 1079

EP - 1086

JO - Journal of Cancer

JF - Journal of Cancer

SN - 1837-9664

IS - 11

ER -