TY - JOUR
T1 - Molecular classification of breast phyllodes tumors
T2 - Validation of the histologic grading scheme and insights into malignant progression
AU - Ang, Mei Kim
AU - Ooi, Aik Seng
AU - Thike, Aye Aye
AU - Tan, Patrick
AU - Zhang, Zhongfa
AU - Dykema, Karl
AU - Furge, Kyle
AU - Teh, Bin Tean
AU - Tan, Puay Hoon
N1 - Funding Information:
Acknowledgments This study was supported by grants from the Singapore Cancer Syndicate MS004 and MS04R. We would also like to acknowledge the National Cancer Centre Foundation, Singapore Millennium Foundation, and the Van Andel Foundation for their continued support. We thank our surgical colleagues for providing the fresh tissue samples.
PY - 2011/9
Y1 - 2011/9
N2 - Phyllodes tumors of the breast are rare fibroepithelial neoplasms with a potential for recurrence. Current histological classification is not always predictive of clinical behavior. The aim of this study was to identify genetic changes associated with the development of borderline and malignant phyllodes tumors in an Asian population, and to assess if genetic data supported the categorization of these tumors into the existing three grades of benign, borderline, and malignant. Expression profiling of 21 phyllodes tumors (6 benign, 10 borderline, 5 malignant) was performed using Affymetrix U133Plus 2.0 GeneChips®. Gene expression among benign, borderline, and malignant tumors was compared and a 29 gene list was able to classify them according to their histologic grade. Among these 29 genes are those responsible for matrix formation, cell adhesion, epidermis formation, and cell proliferation. Comparative genomic microarray analysis showed that the most common chromosomal alteration associated with borderline and malignant tumors was 1q gain, and an increasing number of chromosomal changes was noted with increasing histological grade. Upregulation of HOXB13 was seen in malignant relative to borderline phyllodes tumors and further investigated by immunohistochemistry in a corresponding set of formalin-fixed, paraffin-embedded tumors. HOXB13 protein overexpression was found to be correlated with stromal hypercellularity and atypia (P = 0.03, P = 0.039, respectively) and may be implicated in the development of malignant phyllodes tumors.
AB - Phyllodes tumors of the breast are rare fibroepithelial neoplasms with a potential for recurrence. Current histological classification is not always predictive of clinical behavior. The aim of this study was to identify genetic changes associated with the development of borderline and malignant phyllodes tumors in an Asian population, and to assess if genetic data supported the categorization of these tumors into the existing three grades of benign, borderline, and malignant. Expression profiling of 21 phyllodes tumors (6 benign, 10 borderline, 5 malignant) was performed using Affymetrix U133Plus 2.0 GeneChips®. Gene expression among benign, borderline, and malignant tumors was compared and a 29 gene list was able to classify them according to their histologic grade. Among these 29 genes are those responsible for matrix formation, cell adhesion, epidermis formation, and cell proliferation. Comparative genomic microarray analysis showed that the most common chromosomal alteration associated with borderline and malignant tumors was 1q gain, and an increasing number of chromosomal changes was noted with increasing histological grade. Upregulation of HOXB13 was seen in malignant relative to borderline phyllodes tumors and further investigated by immunohistochemistry in a corresponding set of formalin-fixed, paraffin-embedded tumors. HOXB13 protein overexpression was found to be correlated with stromal hypercellularity and atypia (P = 0.03, P = 0.039, respectively) and may be implicated in the development of malignant phyllodes tumors.
KW - Comparative genomic microarray analysis
KW - Gene expression
KW - Histological grade
KW - Malignant progression
KW - Phyllodes tumors
UR - http://www.scopus.com/inward/record.url?scp=80052645745&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052645745&partnerID=8YFLogxK
U2 - 10.1007/s10549-010-1204-5
DO - 10.1007/s10549-010-1204-5
M3 - Article
C2 - 20945089
AN - SCOPUS:80052645745
SN - 0167-6806
VL - 129
SP - 319
EP - 329
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -