Clinical significance of epidermal growth factor receptor protein overexpression and gene copy number gains in prostate cancer.
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Clinical significance of epidermal growth factor receptor protein overexpression and gene copy number gains in prostate cancer. / Schlomm, Thorsten; Kirstein, Patrick; Iwers, Liv; Daniel, Birte; Steuber, Thomas; Walz, Jochen; Chun, Felix; Haese, Alexander; Köllermann, Jens; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Simon, Ronald; Erbersdobler, Andreas.
in: CLIN CANCER RES, Jahrgang 13(22 Pt 1), 2007, S. 6579-6584.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Clinical significance of epidermal growth factor receptor protein overexpression and gene copy number gains in prostate cancer.
AU - Schlomm, Thorsten
AU - Kirstein, Patrick
AU - Iwers, Liv
AU - Daniel, Birte
AU - Steuber, Thomas
AU - Walz, Jochen
AU - Chun, Felix
AU - Haese, Alexander
AU - Köllermann, Jens
AU - Graefen, Markus
AU - Huland, Hartwig
AU - Sauter, Guido
AU - Simon, Ronald
AU - Erbersdobler, Andreas
PY - 2007
Y1 - 2007
N2 - PURPOSE: The epidermal growth factor receptor (EGFR) is a protein involved in the tumor progression of many cancer types and is an important therapeutic target. To determine its role in prostate cancer, we analyzed 2,497 prostate cancers on the DNA and protein level. EXPERIMENTAL DESIGN: Tissue samples from each tumor were brought into a tissue microarray and analyzed by immunohistochemistry and fluorescence in situ hybridization. A subset of cancers was also sequenced for EGFR exon 18 to 21 mutations. RESULTS: Detectable EGFR expression was found in 18% of cancers and was significantly associated with high grade, advanced stage, and high risk for prostate-specific antigen recurrence in univariate analysis (P <0.0001, each). Fluorescence in situ hybridization analysis with a dual-labeling probe for centromere 7 and EGFR showed increased EGFR copy number in 3.3% of cases. EGFR copy number gains were mostly due to an overrepresentation of the entire chromosome and were associated with EGFR protein expression (P <0.0001), high grade (P <0.0001), and advanced stage (P = 0.0056). Only one cancer had a high-level amplification (>20 EGFR gene copies per cell). This amplification was heterogeneous, involving only approximately 30% of the cancer volume. EGFR mutations were not found in 35 of the cases analyzed. CONCLUSION: Increased EGFR expression is often seen in prostate cancer and is associated with poor prognosis. The significant association of EGFR copy number gains with protein expression argues for the significant role of minimal gene copy number changes for protein expression. Although EGFR expression was not an independent prognostic variable, the potential utility of anti-EGFR medications might be worth further investigation in EGFR-expressing prostate cancer.
AB - PURPOSE: The epidermal growth factor receptor (EGFR) is a protein involved in the tumor progression of many cancer types and is an important therapeutic target. To determine its role in prostate cancer, we analyzed 2,497 prostate cancers on the DNA and protein level. EXPERIMENTAL DESIGN: Tissue samples from each tumor were brought into a tissue microarray and analyzed by immunohistochemistry and fluorescence in situ hybridization. A subset of cancers was also sequenced for EGFR exon 18 to 21 mutations. RESULTS: Detectable EGFR expression was found in 18% of cancers and was significantly associated with high grade, advanced stage, and high risk for prostate-specific antigen recurrence in univariate analysis (P <0.0001, each). Fluorescence in situ hybridization analysis with a dual-labeling probe for centromere 7 and EGFR showed increased EGFR copy number in 3.3% of cases. EGFR copy number gains were mostly due to an overrepresentation of the entire chromosome and were associated with EGFR protein expression (P <0.0001), high grade (P <0.0001), and advanced stage (P = 0.0056). Only one cancer had a high-level amplification (>20 EGFR gene copies per cell). This amplification was heterogeneous, involving only approximately 30% of the cancer volume. EGFR mutations were not found in 35 of the cases analyzed. CONCLUSION: Increased EGFR expression is often seen in prostate cancer and is associated with poor prognosis. The significant association of EGFR copy number gains with protein expression argues for the significant role of minimal gene copy number changes for protein expression. Although EGFR expression was not an independent prognostic variable, the potential utility of anti-EGFR medications might be worth further investigation in EGFR-expressing prostate cancer.
M3 - SCORING: Zeitschriftenaufsatz
VL - 13(22 Pt 1)
SP - 6579
EP - 6584
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
ER -
