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

Journal of Experimental & Clinical Cancer Research

Markus Moehler³  Marko Kornmann²  Peter Robert Galle³  Arthur Hoffman⁵  Arndt Weinmann³  Johannes Wilhelm Rey⁵  Karl-Heinrich Link⁴  Arno Schad¹  Jens Martin Kittner³  Wiebke Neumann³  Michael Schwarz³  Mario Trautmann³  Susanne Bauer³  Andrea Formentini²  Annett Maderer³  Thomas Thomaidis³ 

[1] Department of Pathology, Johannes-Gutenberg University, Mainz, Germany;Department of Surgery, University Hospital, Ulm, Germany;I. Medical Department, Johannes-Gutenberg University, Mainz, Germany;Department of Surgery, Asklepios Clinic, Wiesbaden, Germany;Medical Department, Marienhospital, Frankfurt, Germany

关键词: Adjuvant chemotherapy;    Hif-1 alpha;    PTEN;    Epiregulin;    Amphiregulin;    VEGFR;    EGFR;    Predictive biomarkers;    Stage II/III colorectal cancer;   

Others  :  1145581
DOI  :  10.1186/s13046-014-0083-8

 received in 2014-07-08, accepted in 2014-09-24,  发布年份 2014

【 摘 要 】

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 ?, 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 ?, 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 ? (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 ? 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.

【 授权许可】

   
2014 Thomaidis et al.; licensee BioMed Central Ltd.

【 图 表 】

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