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Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer

  • Authors:
    • Emanuel Buck
    • Martin Sprick
    • Matthias M. Gaida
    • Carsten Grüllich
    • Tim Frederik Weber
    • Esther Herpel
    • Thomas Bruckner
    • Ronald Koschny
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, University Hospital Heidelberg, D‑69120 Heidelberg, Germany, HI‑STEM gGmbH/German Cancer Research Center Heidelberg (MRS), D‑69120 Heidelberg, Germany, Department of Pathology, National Center for Tumor Diseases, University Hospital Heidelberg, D‑69120 Heidelberg, Germany, Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, D‑69120 Heidelberg, Germany, Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, D‑69120 Heidelberg, Germany, Institute for Medical Biometry and Informatics, University of Heidelberg, D‑69120 Heidelberg, Germany
    Copyright: © Buck et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3890-3898
    |
    Published online on: February 14, 2019
       https://doi.org/10.3892/ol.2019.10043
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Abstract

Recently, a tumor‑autonomous cytochrome P450 (CYP)‑3A5‑mediated resistance to cancer therapy has been demonstrated in pancreatic ductal adenocarcinoma. Expression of CYP3A5, which is involved in the degradation of irinotecan, has also been reported in colorectal cancer (CRC). The aim of the present study was to analyze CYP3A5 expression in the normal colon, colon adenoma, CRC and normal tissues, as well as to examine whether CYP3A5 expression in CRC has an impact on tumor response to irinotecan treatment. Immunohistochemistry was used to assess 85 tissue samples from 65 patients with CRC, along with 15 samples of normal colon and 45 samples of colon adenoma (including tubular, tubulovillous, and sessile serrated adenomas), and a tissue microarray (TMA) comprised of 26 different normal tissue types. Expression of CYP3A5 was evaluated with a semi‑quantitative score. Tumor response to irinotecan therapy was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. In normal tissues, CYP3A5 was expressed in epithelial cells of the colon, gallbladder, kidney, liver, small intestine, stomach, thyroid gland and tonsil, as well as in nerves. Expression in colon mucosa was heterogeneous, with only weak staining in the minority of specimens. CYP3A5 exhibited markedly higher expression in adenomas compared with normal colon tissues. A statistically significant inverse correlation was identified between CYP3A5 expression in CRC tissues and tumor response to irinotecan therapy. Irinotecan treatment itself did not alter CYP3A5 expression in CRC tissues. As CYP3A5 is involved in the degradation of irinotecan, the significantly higher intratumoral expression of CYP3A5 in patients with CRC who do not respond to irinotecan‑based chemotherapy may indicate a causal role of CYP3A5 in tumor resistance.
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Copy and paste a formatted citation
Spandidos Publications style
Buck E, Sprick M, Gaida MM, Grüllich C, Weber TF, Herpel E, Bruckner T and Koschny R: Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer. Oncol Lett 17: 3890-3898, 2019.
APA
Buck, E., Sprick, M., Gaida, M.M., Grüllich, C., Weber, T.F., Herpel, E. ... Koschny, R. (2019). Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer. Oncology Letters, 17, 3890-3898. https://doi.org/10.3892/ol.2019.10043
MLA
Buck, E., Sprick, M., Gaida, M. M., Grüllich, C., Weber, T. F., Herpel, E., Bruckner, T., Koschny, R."Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer". Oncology Letters 17.4 (2019): 3890-3898.
Chicago
Buck, E., Sprick, M., Gaida, M. M., Grüllich, C., Weber, T. F., Herpel, E., Bruckner, T., Koschny, R."Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer". Oncology Letters 17, no. 4 (2019): 3890-3898. https://doi.org/10.3892/ol.2019.10043
Copy and paste a formatted citation
x
Spandidos Publications style
Buck E, Sprick M, Gaida MM, Grüllich C, Weber TF, Herpel E, Bruckner T and Koschny R: Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer. Oncol Lett 17: 3890-3898, 2019.
APA
Buck, E., Sprick, M., Gaida, M.M., Grüllich, C., Weber, T.F., Herpel, E. ... Koschny, R. (2019). Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer. Oncology Letters, 17, 3890-3898. https://doi.org/10.3892/ol.2019.10043
MLA
Buck, E., Sprick, M., Gaida, M. M., Grüllich, C., Weber, T. F., Herpel, E., Bruckner, T., Koschny, R."Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer". Oncology Letters 17.4 (2019): 3890-3898.
Chicago
Buck, E., Sprick, M., Gaida, M. M., Grüllich, C., Weber, T. F., Herpel, E., Bruckner, T., Koschny, R."Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer". Oncology Letters 17, no. 4 (2019): 3890-3898. https://doi.org/10.3892/ol.2019.10043
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