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.
  
  
  CONCLUSIONS
  In metastatic CRC, ABC-transporter expression in the primary tumour does not predict irinotecan response.
authors.affiliation: 1. Department of Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Trumpi
authors.affiliation: 1. Department of Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
authors.forename: B L
authors.initials: BL
authors.lastname: Emmink
authors.affiliation: 1. Department of Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Prins
authors.affiliation: 2. Department of Medical Oncology, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands ; 4. Department of Medical Oncology, Academic Medical Centre, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
authors.forename: M G H
authors.initials: MG
authors.lastname: van Oijen
authors.affiliation: 3. Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: van Diest
authors.affiliation: 4. Department of Medical Oncology, Academic Medical Centre, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
authors.forename: C J A
authors.initials: CJ
authors.lastname: Punt
authors.affiliation: 2. Department of Medical Oncology, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Koopman
authors.affiliation: 1. Department of Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
authors.forename: O
authors.initials: O
authors.lastname: Kranenburg
authors.affiliation: 1. Department of Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
authors.forename: I H M Borel
authors.initials: IH
authors.lastname: Rinkes
keywords: ABC-transporters; ABCB1; ABCG2; CAIRO; Irinotecan; chemotherapy; metastatic colorectal cancer