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Recent insights into the molecular pathogenesis of mammary phyllodes tumours

Abstract

Phyllodes tumours (PTs) of the breast are true biphasic neoplasms within which interactions between the epithelium and stroma are critical for tumour development and progression. Despite numerous studies reporting the results of ancillary marker investigations in PTs, the current histological grading systems remain unreliable at predicting clinical outcome even when supplemented by these markers. As a consequence, there has been much interest in the prospect of using molecular/genetic techniques to develop a more robust "grading" system. This review focuses on recent cytogenetic and molecular studies investigating the pathogenesis of PTs and those correlating molecular findings with clinicopathological features of the tumours. Recent data highlight that intratumoural genetic heterogeneity is common in PTs and may account for the reported lack of correlation between histological grading and clinical behaviour. The entire spectrum of molecular aberrations in PTs are yet to be fully defined, however recent array-based studies using comparative genomic hybridisation have reported that copy number changes increase with the progression from benign PT to malignancy. Tumour recurrence and progression is likely to reflect the presence of under-recognised subclones. p(16INK4a) (CDKN2A) inactivation also appears to be important in PT pathogenesis. Further additional studies will be required to identify and validate new prognostic markers and therapeutic targets in order to improve the diagnosis, classification, prediction of outcome and management of patients with this rare neoplasm. Data generated from modern sequencing technologies are likely to provide new insights into the disease and assist in this endeavour.

Type Journal
ISBN 1472-4146 (Electronic) 0021-9746 (Linking)
Authors Karim, R. Z.; O'Toole, S. A.; Scolyer, R. A.; Cooper, C. L.; Chan, B.; Selinger, C.; Yu, B.; Carmalt, H.; Mak, C.; Tse, G. M.; Tan, P. H.; Putti, T. C.; Lee, C. S.;
Publisher Name J CLIN PATHOL
Published Date 2013-12-01 00:00:00
Published Volume 66
Published Issue 6
Published Pages 496-505
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?12162_12685/J Clin Pathol-2013-Karim-496-505.pdf