Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression

Christian Kersting; Arno Kuijper; Hartmut Schmidt; Jens Packeisen; Cornelia Liedtke; Nicola Tidow; Christian Gustmann; Bernd Hinrichs; Pia Wülfing; Joke Tio; Werner Boecker; Paulus Joannes van Diest; Burkhard Brandt; Horst Buerger

doi:10.1038/labinvest.3700358

Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression

Christian Kersting, Arno Kuijper, Hartmut Schmidt, Jens Packeisen, Cornelia Liedtke, Nicola Tidow, Christian Gustmann, Bernd Hinrichs, Pia Wülfing, Joke Tio, Werner Boecker, Paulus Joannes van Diest, Burkhard Brandt, Horst Buerger

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Abstract

Phyllodes tumors of the breast are rare biphasic tumors with the potential for invasion and metastatic spread. An important role of the epidermal growth factor receptor (EGFR) in phyllodes tumors has been proposed. However, detailed pathogenetic mechanisms remained unclear. We investigated 58 phyllodes tumors of the breast (40 benign, 10 borderline and eight malignant) by means of egfr fluorescence in situ hybridization (FISH) and gene dosage PCR for a regulatory sequence within intron 1 of egfr. Immunohistochemical staining was performed for EGFR, p16, p21, p27, p53, c-myc, Cyclin A, Cyclin D1, Cyclin E, c-kit and Ki67. Immunopositivity for EGFR was detected in 19% of phyllodes tumors (75% of all malignant tumors) in stromal tumor cells but not in the epithelial component. Whole-gene amplifications were seen by FISH in 15.8% (in stromal cells only) and intron 1 amplifications by gene dosage PCR in as much as 41.8% of all phyllodes tumors. Significant correlations were seen between tumor grade on the one hand and EGFR overexpression (P = 0.001) and intron 1 amplifications (P < 0.05) on the other. EGFR overexpression further correlated positively with immunohistochemical staining for p53, p16, Cyclin A, Cyclin E, Ki67 and c-kit. Presence of intron 1 amplifications correlated with p16 (P < 0.01), p21 (P = 0.009) and p53 immunoreactivity (P < 0.001). Neither EGFR overexpression nor whole-gene amplification was observed in a control series of 167 fibroadenomas and only one of 43 (2.3%) exhibited intron 1 amplification in gene dosage PCR. In conclusion, our results show for the first time that activating mutations in and overexpression of egfr are associated with the progression in grade of phyllodes tumors of the breast. The observed association between intron 1 amplification and overexpression of EGFR provides further insight into regulation mechanisms of EGFR overexpression.

Original language	English (US)
Pages (from-to)	54-61
Number of pages	8
Journal	Laboratory Investigation
Volume	86
Issue number	1
DOIs	https://doi.org/10.1038/labinvest.3700358
State	Published - Jan 2006
Externally published	Yes

Keywords

Amplification
Egfr
Expression
Immunohistochemistry
Phyllodes tumor

ASJC Scopus subject areas

Molecular Biology
Pathology and Forensic Medicine
Cell Biology

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10.1038/labinvest.3700358

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Kersting, C., Kuijper, A., Schmidt, H., Packeisen, J., Liedtke, C., Tidow, N., Gustmann, C., Hinrichs, B., Wülfing, P., Tio, J., Boecker, W., van Diest, P. J., Brandt, B., & Buerger, H. (2006). Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression. Laboratory Investigation, 86(1), 54-61. https://doi.org/10.1038/labinvest.3700358

Kersting, C, Kuijper, A, Schmidt, H, Packeisen, J, Liedtke, C, Tidow, N, Gustmann, C, Hinrichs, B, Wülfing, P, Tio, J, Boecker, W, van Diest, PJ, Brandt, B & Buerger, H 2006, 'Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression', Laboratory Investigation, vol. 86, no. 1, pp. 54-61. https://doi.org/10.1038/labinvest.3700358

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title = "Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression",

abstract = "Phyllodes tumors of the breast are rare biphasic tumors with the potential for invasion and metastatic spread. An important role of the epidermal growth factor receptor (EGFR) in phyllodes tumors has been proposed. However, detailed pathogenetic mechanisms remained unclear. We investigated 58 phyllodes tumors of the breast (40 benign, 10 borderline and eight malignant) by means of egfr fluorescence in situ hybridization (FISH) and gene dosage PCR for a regulatory sequence within intron 1 of egfr. Immunohistochemical staining was performed for EGFR, p16, p21, p27, p53, c-myc, Cyclin A, Cyclin D1, Cyclin E, c-kit and Ki67. Immunopositivity for EGFR was detected in 19% of phyllodes tumors (75% of all malignant tumors) in stromal tumor cells but not in the epithelial component. Whole-gene amplifications were seen by FISH in 15.8% (in stromal cells only) and intron 1 amplifications by gene dosage PCR in as much as 41.8% of all phyllodes tumors. Significant correlations were seen between tumor grade on the one hand and EGFR overexpression (P = 0.001) and intron 1 amplifications (P < 0.05) on the other. EGFR overexpression further correlated positively with immunohistochemical staining for p53, p16, Cyclin A, Cyclin E, Ki67 and c-kit. Presence of intron 1 amplifications correlated with p16 (P < 0.01), p21 (P = 0.009) and p53 immunoreactivity (P < 0.001). Neither EGFR overexpression nor whole-gene amplification was observed in a control series of 167 fibroadenomas and only one of 43 (2.3%) exhibited intron 1 amplification in gene dosage PCR. In conclusion, our results show for the first time that activating mutations in and overexpression of egfr are associated with the progression in grade of phyllodes tumors of the breast. The observed association between intron 1 amplification and overexpression of EGFR provides further insight into regulation mechanisms of EGFR overexpression.",

keywords = "Amplification, Egfr, Expression, Immunohistochemistry, Phyllodes tumor",

author = "Christian Kersting and Arno Kuijper and Hartmut Schmidt and Jens Packeisen and Cornelia Liedtke and Nicola Tidow and Christian Gustmann and Bernd Hinrichs and Pia W{\"u}lfing and Joke Tio and Werner Boecker and {van Diest}, {Paulus Joannes} and Burkhard Brandt and Horst Buerger",

year = "2006",

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doi = "10.1038/labinvest.3700358",

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T1 - Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression

AU - Kersting, Christian

AU - Kuijper, Arno

AU - Schmidt, Hartmut

AU - Packeisen, Jens

AU - Liedtke, Cornelia

AU - Tidow, Nicola

AU - Gustmann, Christian

AU - Hinrichs, Bernd

AU - Wülfing, Pia

AU - Tio, Joke

AU - Boecker, Werner

AU - van Diest, Paulus Joannes

AU - Brandt, Burkhard

AU - Buerger, Horst

PY - 2006/1

Y1 - 2006/1

N2 - Phyllodes tumors of the breast are rare biphasic tumors with the potential for invasion and metastatic spread. An important role of the epidermal growth factor receptor (EGFR) in phyllodes tumors has been proposed. However, detailed pathogenetic mechanisms remained unclear. We investigated 58 phyllodes tumors of the breast (40 benign, 10 borderline and eight malignant) by means of egfr fluorescence in situ hybridization (FISH) and gene dosage PCR for a regulatory sequence within intron 1 of egfr. Immunohistochemical staining was performed for EGFR, p16, p21, p27, p53, c-myc, Cyclin A, Cyclin D1, Cyclin E, c-kit and Ki67. Immunopositivity for EGFR was detected in 19% of phyllodes tumors (75% of all malignant tumors) in stromal tumor cells but not in the epithelial component. Whole-gene amplifications were seen by FISH in 15.8% (in stromal cells only) and intron 1 amplifications by gene dosage PCR in as much as 41.8% of all phyllodes tumors. Significant correlations were seen between tumor grade on the one hand and EGFR overexpression (P = 0.001) and intron 1 amplifications (P < 0.05) on the other. EGFR overexpression further correlated positively with immunohistochemical staining for p53, p16, Cyclin A, Cyclin E, Ki67 and c-kit. Presence of intron 1 amplifications correlated with p16 (P < 0.01), p21 (P = 0.009) and p53 immunoreactivity (P < 0.001). Neither EGFR overexpression nor whole-gene amplification was observed in a control series of 167 fibroadenomas and only one of 43 (2.3%) exhibited intron 1 amplification in gene dosage PCR. In conclusion, our results show for the first time that activating mutations in and overexpression of egfr are associated with the progression in grade of phyllodes tumors of the breast. The observed association between intron 1 amplification and overexpression of EGFR provides further insight into regulation mechanisms of EGFR overexpression.

AB - Phyllodes tumors of the breast are rare biphasic tumors with the potential for invasion and metastatic spread. An important role of the epidermal growth factor receptor (EGFR) in phyllodes tumors has been proposed. However, detailed pathogenetic mechanisms remained unclear. We investigated 58 phyllodes tumors of the breast (40 benign, 10 borderline and eight malignant) by means of egfr fluorescence in situ hybridization (FISH) and gene dosage PCR for a regulatory sequence within intron 1 of egfr. Immunohistochemical staining was performed for EGFR, p16, p21, p27, p53, c-myc, Cyclin A, Cyclin D1, Cyclin E, c-kit and Ki67. Immunopositivity for EGFR was detected in 19% of phyllodes tumors (75% of all malignant tumors) in stromal tumor cells but not in the epithelial component. Whole-gene amplifications were seen by FISH in 15.8% (in stromal cells only) and intron 1 amplifications by gene dosage PCR in as much as 41.8% of all phyllodes tumors. Significant correlations were seen between tumor grade on the one hand and EGFR overexpression (P = 0.001) and intron 1 amplifications (P < 0.05) on the other. EGFR overexpression further correlated positively with immunohistochemical staining for p53, p16, Cyclin A, Cyclin E, Ki67 and c-kit. Presence of intron 1 amplifications correlated with p16 (P < 0.01), p21 (P = 0.009) and p53 immunoreactivity (P < 0.001). Neither EGFR overexpression nor whole-gene amplification was observed in a control series of 167 fibroadenomas and only one of 43 (2.3%) exhibited intron 1 amplification in gene dosage PCR. In conclusion, our results show for the first time that activating mutations in and overexpression of egfr are associated with the progression in grade of phyllodes tumors of the breast. The observed association between intron 1 amplification and overexpression of EGFR provides further insight into regulation mechanisms of EGFR overexpression.

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KW - Expression

KW - Immunohistochemistry

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Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression

Abstract

Keywords

ASJC Scopus subject areas

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