High EGFR mRNA expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy.
Pancreatic ductal adenocarcinoma (PDAC) still presents a major therapeutic challenge and a phase III clinical trial has revealed that the combination of gemcitabine and a human epidermal growth factor receptor type I (HER1/EGFR) targeting agent presented a significant benefit compared to treatment with gemcitabine alone. The aim of this study was to investigate EGFR mRNA expression in resected PDAC tissues and its correlation with patient prognosis. We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 88 patients with PDAC who underwent pancreatectomy, and measured EGFR mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction. The high-level EGFR group had significantly shorter disease-free-survival (p=0.029) and overall-survival (p=0.014) as shown by univariate analyses, although these did not reach statistical significance, as shown by multivariate analyses. However, we found that high EGFR expression was an independent prognostic factor in patients receiving gemcitabine-based adjuvant chemotherapy (p=0.023). Furthermore, we measured EGFR mRNA levels in 20 endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytological specimens. Altered EGFR levels were distinguishable in microdissected neoplastic cells from EUS-FNA cytological specimens compared to those in whole cell pellets. In conclusion, quantitative analysis of EGFR mRNA expression using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytological specimens could be useful in predicting prognosis and sensitivity to gemcitabine in PDAC patients.
Department of Surgery and Oncology, Kyushu University, Fukuoka, Japan.
Hayato
H
Fujita
Kenoki
K
Ohuchida
Kazuhiro
K
Mizumoto
Soichi
S
Itaba
Tetsuhide
T
Ito
Kohei
K
Nakata
Jun
J
Yu
Tadashi
T
Kayashima
Akifumi
A
Hayashi
Ryota
R
Souzaki
Tatsuro
T
Tajiri
Manabu
M
Onimaru
Tatsuya
T
Manabe
Takao
T
Ohtsuka
Masao
M
Tanaka
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics; D000093542:Gemcitabine
D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D003841:Deoxycytidine; D066246:ErbB Receptors; D000093542:Gemcitabine