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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: Molecular markers for prognosis in neoadjuvantly treated EAC patients have not been identified yet.Data were correlated with clinical and histopathological response, disease-free and overall survival.Furthermore, EGFR overexpression is involved in resistance to cisplatin-based neoadjuvant chemotherapy.

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 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.
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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.

Mentions: We further evaluated the influence of EGFR protein expression in neoadjuvant chemotherapy-treated patients as a molecular factor for survival prognosis. A statistically significant association between low EGFR expression levels (EGFR-low) and disease-free survival (p=0.0152) and overall survival (p=0.0036) was noted in responders and non-responders (Figure 2A), although responders had a significantly better prognosis than non-responders. In cases where patients did not respond to chemotherapy but had low EGFR protein expression, after surviving the first two years after therapy, their disease-free and overall survival was as good as that for responder patients. In contrast to these findings, in patients with high EGFR expression, the prognosis for responders was as poor as that for non-responders (Figure 2C). Thus, neoadjuvant therapy responders with a putative good prognosis were identified as actually having a poor prognosis after neoadjuvant therapy according to EGFR overexpression.


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

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

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.
Mentions: We further evaluated the influence of EGFR protein expression in neoadjuvant chemotherapy-treated patients as a molecular factor for survival prognosis. A statistically significant association between low EGFR expression levels (EGFR-low) and disease-free survival (p=0.0152) and overall survival (p=0.0036) was noted in responders and non-responders (Figure 2A), although responders had a significantly better prognosis than non-responders. In cases where patients did not respond to chemotherapy but had low EGFR protein expression, after surviving the first two years after therapy, their disease-free and overall survival was as good as that for responder patients. In contrast to these findings, in patients with high EGFR expression, the prognosis for responders was as poor as that for non-responders (Figure 2C). Thus, neoadjuvant therapy responders with a putative good prognosis were identified as actually having a poor prognosis after neoadjuvant therapy according to EGFR overexpression.

Bottom Line: Molecular markers for prognosis in neoadjuvantly treated EAC patients have not been identified yet.Data were correlated with clinical and histopathological response, disease-free and overall survival.Furthermore, EGFR overexpression is involved in resistance to cisplatin-based neoadjuvant chemotherapy.

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