Epidermal growth factor receptor (EGFR) is highly conserved in pancreatic cancer.
BACKGROUND
Pancreatic cancer remains a deadly disease, and the vast majority of pancreatic cancer patients are not candidates for treatment with curative intent. Erlotinib, an EGFR-specific tyrosine kinase inhibitor, was approved recently for use in patients with pancreatic cancer. Somatic mutations in the EGFR gene appear to predict survival and response to tyrosine kinase inhibitor therapy in a subset of patients with non-small-cell lung cancer (NSCLC).


METHODS
The purpose of this study was to characterize EGFR mutations in pancreatic adenocarcinoma. EGFR TK mutations were analyzed in 9 pancreatic carcinoma cell lines and 31 clinical specimens from patients with pancreatic cancer who underwent resection. Using laser capture microdissection, tumor cells from patients were harvested selectively for genomic DNA extraction. Mutations were examined by direct sequencing of exons 18-21.


RESULTS
Of 9 pancreatic cancer cell lines, 6 had either 2454G>A or 2361G>A mutations in exon 20. Of 31 patients, 25 patients had 2361G>A in exon 20, and 1 patient had 2508C>T in exon 21. All were silent mutations.


CONCLUSIONS
The EGFR tyrosine kinase domain is highly conserved in pancreatic cancer. The association among EGFR mutation status, clinical prognosis, and response to anti-EGFR therapy described in NSCLC may not be applicable to pancreatic cancer. This observation does not diminish the possible role of anti-EGFR therapy in pancreatic cancer because there remains a need to explore alternative explanations for pancreatic cancer aberrant EGFR pathway activation such as ligand overexpression, gene amplification, and loss of inhibitory mechanisms.
Tzeng
Ching-Wei D
CW
Department of Surgery, University of Alabama at Birmingham, Birmingham, Ala, USA.
Frolov
Andrey
A
Frolova
Natalya
N
Jhala
Nirag C
NC
Howard
J Harrison
JH
Buchsbaum
Donald J
DJ
Vickers
Selwyn M
SM
Heslin
Martin J
MJ
Arnoletti
J Pablo
JP
D000230:Adenocarcinoma / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000378:metabolism*
D066246:ErbB Receptors