Abstract
Background: Epidermal growth factor receptor (EGFR) has a highly polymorphic CA repeat region that affects transcription efficiency and anti-EGFR drug sensitivity in carcinomas. Erlotinib is an EGFR tyrosine kinase inhibitor approved for pancreatic cancer treatment. We analyzed the impact of EGFR intron 1 CA repeat lengths in pancreatic cancer clinical outcome and in vitro response to erlotinib. Methods: Allele-specific EGFR intron 1 lengths were analyzed in 30 microdissected pancreatic cancer surgical specimens, matched peripheral blood samples, and 9 pancreatic cancer cell lines treated with erlotinib. CA repeat lengths were correlated with survival, tumor parameters, molecular markers of EGFR pathway activation, and in vitro antiproliferative effects of erlotinib. Results: Both patient samples and cell lines displayed the full spectrum of EGFR CA repeat lengths (14-22 per allele). Patients with shorter sum of total CA repeats (<36) had worse median survival than patients with ≥36 repeats (13.7 vs 30.6 months, P = .002). Shorter patient EGFR intron 1 length correlated with EGFR expression (P = .026). Tumor intron 1 length was identical to that of matched peripheral blood specimens. There was no correlation between EGFR intron 1 length and pancreatic cancer stage, nodal status, grade, or expression of p-EGFR, p-ERK and p-Akt. Shorter EGFR intron 1 length was associated with in vitro response to erlotinib treatment (P = .02). Conclusions: Shorter EGFR intron 1 CA repeat length is associated with worse pancreatic cancer clinical prognosis and in vitro response to erlotinib. EGFR intron 1 length can be reliably measured in peripheral blood and may translate into a quantitative predictive marker of both pancreatic cancer aggressiveness and erlotinib sensitivity.
Original language | English (US) |
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Pages (from-to) | 2150-2158 |
Number of pages | 9 |
Journal | Annals of surgical oncology |
Volume | 14 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2007 |
Externally published | Yes |
Keywords
- EGFR
- Epidermal growth factor receptor
- Erlotinib
- Intron 1
- Pancreatic cancer
- Polymorphism
ASJC Scopus subject areas
- Surgery
- Oncology