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J Gastrointest Oncol. 2013 Mar;4(1):20-9. doi: 10.3978/j.issn.2078-6891.2012.012.

Evaluation of phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and epidermal growth factor receptor (EGFR) gene mutations in pancreaticobiliary adenocarcinoma.

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  • 1Department of Medicine, University at Buffalo, Buffalo, New York, USA;

Abstract

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.

KEYWORDS:

Phosphatidylinositol-3-kinase catalytic subunit (PIK3CA); biliary; cancer; epidermal growth factor receptor (EGFR); mutations; pancreas

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