Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma.

Abstract

BACKGROUND:

The aim of this study was to evaluate the expression of epidermal growth factor receptor (EGFR) and insulinlike growth factor 1 receptor (IGF-1R) proteins and IGF-1R gene copy numbers in pancreatic ductal adenocarcinoma in relation to patients' characteristics and prognosis.

METHODS:

Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue derived from tumor specimens recovered during surgery. Slides were evaluated for membranous EGFR and IGF-1R staining using both the HercepTest and the semiquantitative H-score systems. Chromogenic in situ hybridization was performed to quantify IGF-1R gene copy number. The primary outcome was the association between EGFR expression, IGF-1R expression-in both neoplastic epithelial and stromal cells-or IGF-1R gene copy number and overall survival. Secondary outcomes included associations between EFGR and IGF-1R expression and pathologic variables.

RESULTS:

A total of 105 patients were included. EGFR expression was present in 30.4% of cases and was associated with lymph node metastasis (P = .038). IGF-1R was overexpressed in 53% of tumors and correlated with higher tumor grade (P = .033). High membranous expression of EGFR (P < .001) and/or IGF-1R (P = .004), the cytoplasmic detection of EGFR (P = .027), and high expression levels of IGF-1R in the tumoral stroma (P < .001) were all associated with shorter overall survival, being significantly better in patients who simultaneously do not express membranous EGFR or stromal IGF-1R.

CONCLUSIONS:

EGFR and IGF-1R expression, in neoplastic and stromal cells, seems to be an important prognostic factor.

• Authors: Matias E Valsecchi, Mary McDonald, Jonathan R Brody, Terry Hyslop, Boris Freydin, Charles J Yeo, Charalambos Solomides, Stephen C Peiper, Agnieszka K Witkiewicz
• Journal: Cancer (Cancer) Vol. 118 Issue 14 Pg. 3484-93 (Jul 15 2012) ISSN: 1097-0142 [Electronic] United States
• PMID: 22086503 (Publication Type: Evaluation Study, Journal Article)
• Copyright: Copyright © 2011 American Cancer Society.

Chemical References

• Biomarkers, Tumor
• ErbB Receptors
• Receptor, IGF Type 1

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Carcinoma, Pancreatic Ductal (genetics, mortality)
• ErbB Receptors (genetics, metabolism)
• Female
• Gene Dosage
• Gene Expression
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms (genetics, mortality)
• Prognosis
• Receptor, IGF Type 1 (genetics, metabolism)