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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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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.
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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.

Mentions: The frequency of EGFR overexpression in patients who respond to neoadjuvant chemotherapy was compared with the frequency of EGFR overexpression in EAC patients treated with primary resection without chemotherapy. The percentage of cases with high EGFR expression levels (score 2+ or 3+) was significantly more often found (p=0.0108) in the neoadjuvant chemotherapy-treated cohort (31.4%, 27 of 86 vs. 13.0%, 6 of 46) compared to the primary resection cohort (Table 1). To further assess these findings, we separately compared the responder and the non-responder subgroup with the primary resection cohort. No significant difference in the frequency of EGFR overexpression was detected between chemotherapy-responders and in primary resection patients (p=0.2028; Figure 3A). In contrast, the frequency of EGFR overexpression, was significantly higher in non-responders than in primary resection patients (p=0.0107; Figure 3B).


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)

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

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

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.
Mentions: The frequency of EGFR overexpression in patients who respond to neoadjuvant chemotherapy was compared with the frequency of EGFR overexpression in EAC patients treated with primary resection without chemotherapy. The percentage of cases with high EGFR expression levels (score 2+ or 3+) was significantly more often found (p=0.0108) in the neoadjuvant chemotherapy-treated cohort (31.4%, 27 of 86 vs. 13.0%, 6 of 46) compared to the primary resection cohort (Table 1). To further assess these findings, we separately compared the responder and the non-responder subgroup with the primary resection cohort. No significant difference in the frequency of EGFR overexpression was detected between chemotherapy-responders and in primary resection patients (p=0.2028; Figure 3A). In contrast, the frequency of EGFR overexpression, was significantly higher in non-responders than in primary resection patients (p=0.0107; Figure 3B).

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