TY  - JOUR
A1  - Thomaidis, Thomas
A1  - Maderer, Annett
A1  - Formentini, Andrea
A1  - Bauer, Susanne
A1  - Trautmann, Mario
A1  - Schwarz, Michael
A1  - Neumann, Wiebke
A1  - Kittner, Jens Martin
A1  - Schad, Arno
A1  - Link, Karl-Heinrich
A1  - Rey, Johannes Wilhelm
A1  - Weinmann, Arndt
A1  - Hoffman, Arthur
A1  - Galle, Peter Robert
A1  - Kornmann, Marko
A1  - Möhler, Markus
T1  - Proteins of the VEGFR and EGFR pathway as predictive markers for adjuvant treatment in patients with stage II/III colorectal cancer : results of the FOGT-4 trial
T2  - Journal of experimental & clinical cancer research
N2  - Background: Unlike metastatic colorectal cancer (CRC) there are to date few reports concerning the predictive value of molecular biomarkers on the clinical outcome in stage II/III CRC patients receiving adjuvant chemotherapy. Aim of this study was to assess the predictive value of proteins related with the EGFR- and VEGFR- signalling cascades in these patients.
Methods: The patients' data examined in this study were from the collective of the 5-FU/FA versus 5-FU/FA/irinotecan phase III FOGT-4 trial. Tumor tissues were stained by immunohistochemistry for VEGF-C, VEGF-D, VEGFR-3, Hif-1 α, PTEN, AREG and EREG expression and evaluated by two independent, blinded investigators. Survival analyses were calculated for all patients receiving adjuvant chemotherapy in relation to expression of all makers above.
Results: Patients with negative AREG and EREG expression on their tumor had a significant longer DFS in comparison to AREG/EREG positive ones (p< 0.05). The benefit on DFS in AREG-/EREG- patients was even stronger in the group that received 5-FU/FA/irinotecan as adjuvant treatment (p=0.002). Patients with strong expression of PTEN profited more in terms of OS under adjuvant treatment containing irinotecan (p< 0.05). Regarding markers of the VEGFR- pathway we found no correlation of VEGF-C- and VEGFR-3 expression with clinical outcome. Patients with negative VEGF-D expression had a trend to live longer when treated with 5-FU/FA (p=0.106). Patients who were negative for Hif-1 α, were disease-free in more than 50% at the end of the study and showed significant longer DFS-rates than those positive for Hif-1 α (p=0.007). This benefit was even stronger at the group treated with 5-FU/FA/irinotecan (p=0.026). Finally, AREG-/EREG-/PTEN+ patients showed a trend to live longer under combined treatment combination.
Conclusions: The addition of irinotecan to adjuvant treatment with 5-FU/FA does not provide OS or DFS benefit in patients with stage II/III CRC. Nevertheless, AREG/EREG negative, PTEN positive and Hif-1 α negative patients might profit significantly in terms of DFS from a treatment containing fluoropyrimidines and irinotecan. Our results suggest a predictive value of these biomarkers concerning adjuvant chemotherapy with 5-FU/FA +/− irinotecan in stage II/III colorectal cancer.
KW  - stage II/III colorectal cancer
KW  - predictive biomarkers
KW  - EGFR
KW  - VEGFR
KW  - amphiregulin
KW  - epiregulin
KW  - PTEN
KW  - Hif-1 alpha
KW  - adjuvant chemotherapy
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/35373
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-353738
SN  - 1756-9966
SN  - 0392-9078
N1  - © 2014 Thomaidis et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 33
IS  - 83
PB  - Springer
CY  - Berlin ; Heidelberg
ER  -