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

Matias E. Valsecchi, Mary McDonald, Jonathan R. Brody, Terry Hyslop, Boris Freydin, Charles J. Yeo, Charalambos Solomides, Stephen C. Peiper, Agnieszka K. Witkiewicz

Research output: Contribution to journalArticle

58 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3484-3493
Number of pages10
JournalCancer
Volume118
Issue number14
DOIs
StatePublished - Jul 15 2012

Fingerprint

Growth Factor Receptors
Epidermal Growth Factor Receptor
Adenocarcinoma
Survival
Gene Dosage
Stromal Cells
Staining and Labeling
Neoplasms
Paraffin
Formaldehyde
In Situ Hybridization
Lymph Nodes
Epithelial Cells

Keywords

  • biomarkers
  • EGFR
  • IGF-1R
  • pancreatic cancer
  • prognostic factors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma. / Valsecchi, Matias E.; McDonald, Mary; Brody, Jonathan R.; Hyslop, Terry; Freydin, Boris; Yeo, Charles J.; Solomides, Charalambos; Peiper, Stephen C.; Witkiewicz, Agnieszka K.

In: Cancer, Vol. 118, No. 14, 15.07.2012, p. 3484-3493.

Research output: Contribution to journalArticle

Valsecchi, ME, McDonald, M, Brody, JR, Hyslop, T, Freydin, B, Yeo, CJ, Solomides, C, Peiper, SC & Witkiewicz, AK 2012, 'Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma', Cancer, vol. 118, no. 14, pp. 3484-3493. https://doi.org/10.1002/cncr.26661
Valsecchi, Matias E. ; McDonald, Mary ; Brody, Jonathan R. ; Hyslop, Terry ; Freydin, Boris ; Yeo, Charles J. ; Solomides, Charalambos ; Peiper, Stephen C. ; Witkiewicz, Agnieszka K. / Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma. In: Cancer. 2012 ; Vol. 118, No. 14. pp. 3484-3493.
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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.",
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T1 - Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma

AU - Valsecchi, Matias E.

AU - McDonald, Mary

AU - Brody, Jonathan R.

AU - Hyslop, Terry

AU - Freydin, Boris

AU - Yeo, Charles J.

AU - Solomides, Charalambos

AU - Peiper, Stephen C.

AU - Witkiewicz, Agnieszka K.

PY - 2012/7/15

Y1 - 2012/7/15

N2 - 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.

AB - 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.

KW - biomarkers

KW - EGFR

KW - IGF-1R

KW - pancreatic cancer

KW - prognostic factors

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