评估胰腺胆管腺癌中磷酸肌醇-3-激酶催化亚基（PIK3CA）和表皮生长因子受体（EGFR）基因突变。
Evaluation of phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and epidermal growth factor receptor (EGFR) gene mutations in pancreaticobiliary adenocarcinoma.
机构信息
Department of Medicine, University at Buffalo, Buffalo, New York, USA;
出版信息
J Gastrointest Oncol. 2013 Mar;4(1):20-9. doi: 10.3978/j.issn.2078-6891.2012.012.
BACKGROUND
Phosphatidylinositol-3-kinase (PI3K) activation involves the epidermal growth factor receptor (EGFR) and plays an important role in cell survival signaling in pancreaticobiliary cancer. EGFR gene mutations have been correlated with clinical response to EGFR inhibitors in patients with advanced non-small cell lung cancer. This study examined the prevalence of PIK3CA and EGFR mutations in pancreaticobiliary cancer where erlotinib, an EGFR inhibitor, is approved for therapy.
METHODS
Thirty patients who underwent pancreatectomy for pancreaticobiliary carcinoma were identified. Genomic DNA was extracted from formalin fixed paraffin embedded tumor and adjacent normal tissue, and exons 9 and 20 (for the PIK3CA gene) and exons 18-21 (for the EGFR gene) were amplified by PCR and sequenced. Literature review on EGFR and/or PIK3CA mutations in pancreaticobiliary adenocarcinomas was conducted.
RESULTS
No mutations in either PIK3CA or EGFR genes were identified. The study identified one synonymous single nucleotide polymorphism (SNP) (rs1050171) in the coding region of EGFR. A previously unreported change, suspected to be a SNP, was observed in intron 18 of EGFR (IVS18+15, C>T). Review of the literature showed EGFR mutation rate of 2% and 10.5% in pancreatic and biliary tract carcinomas, respectively. PIK3CA mutations were found in 3.6% and 11.7% of pancreatic and biliary tract carcinomas, respectively.
CONCLUSIONS
A low prevalence of EGFR or PIK3CA mutations exists in pancreatic cancer (<5%), indicating that mutation screening may not be as useful in determining prognosis or response to targeted inhibition.
背景
磷酸肌醇 3-激酶（PI3K）的激活涉及表皮生长因子受体（EGFR），并在胰腺胆管癌的细胞存活信号中发挥重要作用。EGFR 基因突变与晚期非小细胞肺癌患者对 EGFR 抑制剂的临床反应相关。本研究检测了胰腺胆管癌中 PIK3CA 和 EGFR 突变的流行率，其中表皮生长因子受体抑制剂厄洛替尼被批准用于治疗。
方法
确定了 30 名接受胰腺胆管癌切除术的患者。从福尔马林固定石蜡包埋的肿瘤和相邻正常组织中提取基因组 DNA，通过 PCR 扩增 PIK3CA 基因的外显子 9 和 20 以及 EGFR 基因的外显子 18-21，并进行测序。对胰腺胆管腺癌中 EGFR 和/或 PIK3CA 突变进行了文献综述。
结果
未发现 PIK3CA 或 EGFR 基因的突变。该研究在 EGFR 的编码区鉴定出一个同义单核苷酸多态性（SNP）（rs1050171）。在 EGFR 的内含子 18 中观察到一个以前未报道的变化，疑似 SNP（IVS18+15，C>T）。文献回顾显示，胰腺和胆管癌的 EGFR 突变率分别为 2%和 10.5%。在胰腺和胆管癌中分别发现了 3.6%和 11.7%的 PIK3CA 突变。
结论
胰腺癌中 EGFR 或 PIK3CA 突变的发生率较低（<5%），表明突变筛查可能对确定预后或对靶向抑制的反应没有太大帮助。
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