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, Paul Van Diest, Burkhard Brandt, Horst Buerger

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)54-61
Number of pages8
JournalLaboratory Investigation
Volume86
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Fingerprint

Phyllodes Tumor
erbB-1 Genes
Epidermal Growth Factor Receptor
Breast
Introns
Gene Dosage
Neoplasms
Cyclin A
Cyclin E
Gene Amplification
Stromal Cells
Fluorescence In Situ Hybridization
Polymerase Chain Reaction
Staining and Labeling
Fibroadenoma
Cyclin D1
Mutation

Keywords

  • Amplification
  • Egfr
  • Expression
  • Immunohistochemistry
  • Phyllodes tumor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression. / Kersting, Christian; Kuijper, Arno; Schmidt, Hartmut; Packeisen, Jens; Liedtke, Cornelia; Tidow, Nicola; Gustmann, Christian; Hinrichs, Bernd; Wülfing, Pia; Tio, Joke; Boecker, Werner; Van Diest, Paul; Brandt, Burkhard; Buerger, Horst.

In: Laboratory Investigation, Vol. 86, No. 1, 01.2006, p. 54-61.

Research output: Contribution to journalArticle

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, 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
Kersting, Christian ; Kuijper, Arno ; Schmidt, Hartmut ; Packeisen, Jens ; Liedtke, Cornelia ; Tidow, Nicola ; Gustmann, Christian ; Hinrichs, Bernd ; Wülfing, Pia ; Tio, Joke ; Boecker, Werner ; Van Diest, Paul ; Brandt, Burkhard ; Buerger, Horst. / Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression. In: Laboratory Investigation. 2006 ; Vol. 86, No. 1. pp. 54-61.
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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.",
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