High EGFR mRNA expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy
High EGFR mRNA expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy
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DOI：
10.3892/ijo.2011.908
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发表时间：
2011-03-01
影响因子：
5.2
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
--
作者：
Fujita, Hayato;Ohuchida, Kenoki;Tanaka, Masao
胰腺导管腺癌（PDAC）仍然是一个主要的治疗挑战，III期临床试验显示，与吉西他滨单独治疗相比，吉西他滨和人表皮生长因子受体I型（HER 1/EGFR）靶向药物联合治疗具有显著的获益。本研究的目的是研究EGFR mRNA在PDAC切除组织中的表达及其与患者预后的相关性。我们从88例接受胰腺切除术的PDAC患者中获得了正式的固定石蜡包埋（FFPE）组织样本，并通过定量实时逆转录聚合酶链反应测定EGFR mRNA水平。如单变量分析所示，高水平EGFR组的无病生存期（p=0.029）和总生存期（p=0.014）显著较短，但如多变量分析所示，这些均未达到统计学显著性。然而，我们发现EGFR高表达是接受吉西他滨辅助化疗患者的独立预后因素（p=0.023）。此外，我们还检测了20例内镜超声引导下细针穿刺（EUS-FNA）细胞学标本中EGFR mRNA的水平。改变的EGFR水平在EUS-FNA细胞学标本的显微切割肿瘤细胞中与全细胞团块中的EGFR水平相比是可区分的。总之，使用FFPE组织样本和来自EUS-FNA细胞学标本的显微切割肿瘤细胞进行EGFR mRNA表达的定量分析可用于预测PDAC患者的预后和对吉西他滨的敏感性。
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 formal in-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.