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 ¼ 0.001) and intron 1 amplifications (Po0.05) 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 (Po0.01), p21 (P ¼ 0.009) and p53 immunoreactivity (Po0.001). 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.

Fibroepithelial Tumors of the Breast: Pathologic and Immunohistochemical Features and Molecular Mechanisms

“…59 74 EGFR positivity was detected in 19% of PTs (75% of all malignant tumors) in stromal tumor cells but not in the epithelial component, and it was correlated with p53 expression. Like many other biomarkers, the overall low sensitivity can limit its application in daily practice.…”

Phyllodes tumors of the breast segregate in two groups according to genetic criteria

“…23,24 Epidermal growth factor receptor (EGFR) overexpression and amplifications are common in phyllodes tumors. 26 To characterize the genetic changes associated with phyllodes tumors of the breast, we evaluated the genetic imbalances of a series of 30 phyllodes tumors of different histological grades using CGH. Our main objective was to investigate whether the genetic imbalances could help for the evaluation of the malignant potential of these tumors.…”

Amplifications of EGFR gene and protein expression of EGFR, Her-2/neu, c-kit, and androgen receptor in phyllodes tumor of the prostate

“…They also found that EGFR overexpression was associated with progression in the phyllodes tumor of the breast. 3 In this study, we demonstrated frequent and strong EGFR protein expression (four of 11 cases) in the stromal components of prostatic phyllodes tumors. One case had three recurrences before sarcoma emerged.…”

“…A recent study revealed that amplifications of the EGFR gene are common and are associated with tumor progression in phyllodes tumors of the breast. 3 However, a similar analysis has not been performed on prostatic phyllodes tumor. In phyllodes tumors of the breast, c-kit (CD-117) expression is correlated with increased tumor grade and may be useful in predicting recurrent disease.…”