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. 2014 Aug 30;5(16):6620-32.
doi: 10.18632/oncotarget.2268.

Epidermal growth factor receptor (EGFR) is an independent adverse prognostic factor in esophageal adenocarcinoma patients treated with cisplatin-based neoadjuvant chemotherapy

Michaela Aichler  1 , Martin Motschmann  1 , Uta Jütting  2 , Birgit Luber  3 , Karen Becker  3 , Katja Ott  4 , Florian Lordick  5 , Rupert Langer  3 , Marcus Feith  6 , Jörg Rüdiger Siewert  7 , Axel Walch  1
Affiliations

Epidermal growth factor receptor (EGFR) is an independent adverse prognostic factor in esophageal adenocarcinoma patients treated with cisplatin-based neoadjuvant chemotherapy

Michaela Aichler et al. Oncotarget. .

Abstract

Neoadjuvant platin-based therapy is accepted as a standard therapy for advanced esophageal adenocarcinoma (EAC). Patients who respond have a better survival prognosis, but still a significant number of responder patients die from tumor recurrence. Molecular markers for prognosis in neoadjuvantly treated EAC patients have not been identified yet. We investigated the epidermal growth factor receptor (EGFR) in prognosis and chemotherapy resistance in these patients. Two EAC patient cohorts, either treated by neoadjuvant cisplatin-based chemotherapy followed by surgery (n=86) or by surgical resection (n=46) were analyzed for EGFR protein expression and gene copy number. Data were correlated with clinical and histopathological response, disease-free and overall survival. In case of EGFR overexpression, the prognosis for neoadjuvant chemotherapy responders was poor as in non-responders. Responders had a significantly better disease-free survival than non-responders only if EGFR expression level (p=0.0152) or copy number (p=0.0050) was low. Comparing neoadjuvantly treated patients and primary resection patients, tumors of non-responder patients more frequently exhibited EGFR overexpression, providing evidence that EGFR is a factor for indicating chemotherapy resistance. EGFR overexpression and gene copy number are independent adverse prognostic factors for neoadjuvant chemotherapy-treated EAC patients, particularly for responders. Furthermore, EGFR overexpression is involved in resistance to cisplatin-based neoadjuvant chemotherapy.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. EGFR protein expression is associated with prognosis in patients treated with neoadjuvant chemotherapy or primary resection
(A) Disease-free and (B) overall survival of all neoadjuvant chemotherapy-treated patients. (C) Disease-free and (D) overall survival of responding patients. (E) Disease-free and (F) overall survival of non-responding patients. (G) Disease-free and (H) overall survival of primary resection patients. Patients can be stratified as patients with a good survival prognosis if EGFR protein expression is low and patients with a poor survival prognosis if EGFR protein expression is high.
Figure 2
Figure 2. EGFR overexpression and EGFR/Chromosome-7 ratio are molecular factors for stratification of patients after neoadjuvant chemotherapy
(A, B, C, D) Disease-free survival of neoadjuvant chemotherapy-treated patients. (A) Low EGFR protein expression. (B) Low EGFR/Chromosome-7 ratio. (C) High EGFR protein expression. (D) High EGFR/Chromosome-7 ratio. (E, F, G, H) Overall survival of neoadjuvant chemotherapy-treated patients. (E) Low EGFR protein expression. (F) Low EGFR/Chromosome-7 ratio. (G) High EGFR protein expression. (H) High EGFR/Chromosome-7 ratio. Prognosis for neoadjuvant chemotherapy responders was as poor as that for non-responders when EGFR expression level was high. Responders had a significantly better prognosis than non-responders when EGFR expression level or EGFR/Chromosome-7 ratio were low.
Figure 3
Figure 3
Bar graphs depict EGFR expression level distribution (EGFR-high vs. EGFR-low) in comparisons of primary resection patients with neoadjuvant chemotherapy (A) responders and (B) non-responders. EGFR overexpression is more frequent in non-responding patients, and thus, this overexpression can be interpreted as a factor for chemotherapy resistance.
See this image and copyright information in PMC

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