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

Aichler M, Motschmann M, Jütting U, Luber B, Becker K, Ott K, Lordick F, Langer R, Feith M, Siewert JR, Walch A - Oncotarget (2014)

Bottom Line: Data were correlated with clinical and histopathological response, disease-free and overall survival.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.EGFR overexpression and gene copy number are independent adverse prognostic factors for neoadjuvant chemotherapy-treated EAC patients, particularly for responders.

View Article: PubMed Central - PubMed

Affiliation: Research Unit Analytical Pathology- Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, Neuherberg, Germany.

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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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.
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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.

Mentions: EGFR protein expression was significantly associated with outcome in the whole population including neoadjuvant treated and primary resected patients (Figure 1, Table 2). In the neoadjuvant treated group, EGFR protein expression was significantly associated with disease-free survival (p=0.0194; Figure 1A, Table 2). In primary resection patients, a significant association between EGFR protein expression and disease-free survival (p<0.0001; Figure 1G, Table 2) and overall survival (p<0.0001; Figure 1H, Table 2) was identified. Further stratification of the neoadjuvant chemotherapy group into responding and non-responding patients revealed that survival of patients who did not respond to chemotherapy was not associated with EGFR expression (Figure 1E-F, Table 2). In contrast, disease-free and overall survival of responding patients were significantly associated with the EGFR expression status (Figure 1C-D, Table 2). Responding patients with low EGFR expression profit significantly in terms of disease-free (p=0.0015; Figure 1C, Table 2) and overall survival (p=0.0032; Figure 1D, Table 2), while high EGFR expression significantly shortened survival in this subgroup (Figure 1C-D, Table 2).


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

Aichler M, Motschmann M, Jütting U, Luber B, Becker K, Ott K, Lordick F, Langer R, Feith M, Siewert JR, Walch A - Oncotarget (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196151&req=5

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.
Mentions: EGFR protein expression was significantly associated with outcome in the whole population including neoadjuvant treated and primary resected patients (Figure 1, Table 2). In the neoadjuvant treated group, EGFR protein expression was significantly associated with disease-free survival (p=0.0194; Figure 1A, Table 2). In primary resection patients, a significant association between EGFR protein expression and disease-free survival (p<0.0001; Figure 1G, Table 2) and overall survival (p<0.0001; Figure 1H, Table 2) was identified. Further stratification of the neoadjuvant chemotherapy group into responding and non-responding patients revealed that survival of patients who did not respond to chemotherapy was not associated with EGFR expression (Figure 1E-F, Table 2). In contrast, disease-free and overall survival of responding patients were significantly associated with the EGFR expression status (Figure 1C-D, Table 2). Responding patients with low EGFR expression profit significantly in terms of disease-free (p=0.0015; Figure 1C, Table 2) and overall survival (p=0.0032; Figure 1D, Table 2), while high EGFR expression significantly shortened survival in this subgroup (Figure 1C-D, Table 2).

Bottom Line: Data were correlated with clinical and histopathological response, disease-free and overall survival.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.EGFR overexpression and gene copy number are independent adverse prognostic factors for neoadjuvant chemotherapy-treated EAC patients, particularly for responders.

View Article: PubMed Central - PubMed

Affiliation: Research Unit Analytical Pathology- Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, Neuherberg, Germany.

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.

Show MeSH
Related in: MedlinePlus