| AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 2009;1(1):23-34
Review Article
Molecular pathogenesis of progression and recurrence in breast
phyllodes tumors
Ana Richelia Jara-Lazaro, Puay Hoon Tan
Department of Pathology, Singapore General Hospital, Outram Road, Singapore 169608
Received November 22, 2008; accepted November 25, 2008; available online January 1, 2009
Abstract: Breast phyllodes tumors are rare fibroepithelial neoplasms that need to be distinguished from the
common morphologically similar fibroadenomas, because phyllodes tumors can recur and progress to
malignancy. Their potentially recurring and metastasizing behavior is attributed to their stromal characteristics, for
which categorization between benign, borderline and malignant tumors have not been universally established.
Previous clonality studies revealing monoclonal stromal cells versus a polyclonal epithelial component theorized
that phyllodes tumors are mainly stromal neoplasms, possibly arising from fibroadenomas. More recent
chromosomal imbalances in both epithelium and stroma have challenged this theory to favor neoplasia of both
epithelium and stroma, with initial interdependence between the two components. Inverse correlations between
epithelial and stromal overexpression for various biological markers-like estrogen receptor, p53, c-kit, Ki-67,
endothelin-1, epidermal growth factor, heparan sulfate, in addition to findings between epithelial Wnt signalling,
and stromal insulin growth factors and beta-catenin expression, suggest an initial epithelial-stromal
interdependence at the benign phase. Upon progression to malignancy, the stroma is hypothesized to assume
an autonomous growth overriding any epithelial influence. Frequent genetic alterations are chromosomal gains
of 1q and losses at chromosome 13. Acquisition of new genetic imbalances within the tumor consistent with
intratumoral heterogeneity, and subclones within histologically benign phyllodes tumors that recur or metastasize
are the current theories explaining these tumors’ unpredictable clinical behavior. (AJTR811004).
Key Words: Molecular pathogenesis; phyllodes tumors; epithelial-stromal interactions; biological markers;
genetic alterations; subclones
Full Text PDF
Address all correspondence to:
Dr Puay Hoon Tan
Department of Pathology
Singapore General Hospital
Outram Road, Singapore 169608
Tel: 65-63214874
Fax: 65 62226826
E-mail: tan.puay.hoon@sgh.com.sg
Review Article
Molecular pathogenesis of progression and recurrence in breast
phyllodes tumors
Ana Richelia Jara-Lazaro, Puay Hoon Tan
Department of Pathology, Singapore General Hospital, Outram Road, Singapore 169608
Received November 22, 2008; accepted November 25, 2008; available online January 1, 2009
Abstract: Breast phyllodes tumors are rare fibroepithelial neoplasms that need to be distinguished from the
common morphologically similar fibroadenomas, because phyllodes tumors can recur and progress to
malignancy. Their potentially recurring and metastasizing behavior is attributed to their stromal characteristics, for
which categorization between benign, borderline and malignant tumors have not been universally established.
Previous clonality studies revealing monoclonal stromal cells versus a polyclonal epithelial component theorized
that phyllodes tumors are mainly stromal neoplasms, possibly arising from fibroadenomas. More recent
chromosomal imbalances in both epithelium and stroma have challenged this theory to favor neoplasia of both
epithelium and stroma, with initial interdependence between the two components. Inverse correlations between
epithelial and stromal overexpression for various biological markers-like estrogen receptor, p53, c-kit, Ki-67,
endothelin-1, epidermal growth factor, heparan sulfate, in addition to findings between epithelial Wnt signalling,
and stromal insulin growth factors and beta-catenin expression, suggest an initial epithelial-stromal
interdependence at the benign phase. Upon progression to malignancy, the stroma is hypothesized to assume
an autonomous growth overriding any epithelial influence. Frequent genetic alterations are chromosomal gains
of 1q and losses at chromosome 13. Acquisition of new genetic imbalances within the tumor consistent with
intratumoral heterogeneity, and subclones within histologically benign phyllodes tumors that recur or metastasize
are the current theories explaining these tumors’ unpredictable clinical behavior. (AJTR811004).
Key Words: Molecular pathogenesis; phyllodes tumors; epithelial-stromal interactions; biological markers;
genetic alterations; subclones
Full Text PDF
Address all correspondence to:
Dr Puay Hoon Tan
Department of Pathology
Singapore General Hospital
Outram Road, Singapore 169608
Tel: 65-63214874
Fax: 65 62226826
E-mail: tan.puay.hoon@sgh.com.sg
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