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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Partial PTEN deletion is linked to poor prognosis in breast cancer

Authors: P. Lebok, V. Kopperschmidt, M. Kluth, C. Hube-Magg, C. Özden, Taskin B., K. Hussein, A. Mittenzwei, A. Lebeau, I. Witzel, L. Wölber, S. Mahner, F. Jänicke, S. Geist, P. Paluchowski, C. Wilke, U. Heilenkötter, Ronald Simon, Guido Sauter, L. Terracciano, R. Krech, A. von d. Assen, V. Müller, E. Burandt

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Deletions of chromosome 10q23, including the PTEN (phosphatase and tensin homolog) locus, are known to occur in breast cancer, but systematic analyses of its clinical relevance are lacking.

Methods

We thus analyzed a tissue microarray (TMA) with 2,197 breast cancers by fluorescence in-situ hybridization (FISH) using a PTEN-specific probe.

Results

PTEN deletions were detected in 19 % of no special type, 9 % of lobular, 4 % of tubular cancers and 46 % in carcinomas with medullary features. 98.7 % of deletions were heterozygous and only 1.3 % were homozygous. PTEN deletion was significantly linked to advanced tumor stage (p = 0.0054), high-grade (p < 0.0001), high tumor cell proliferation (Ki67 Labeling Index; p < 0.0001), and shortened overall survival (p = 0.0090). PTEN deletions were inversely associated with features of luminal type breast cancers (ER/PR positivity; p < 0.0001 each, and CCND1 amplification; p = 0.0020). PTEN deletions were also strongly linked to amplification of genes involved in the PTEN/AKT pathway such as MYC (p = 0.0430) and HER2 (p = 0.0065). Remarkably the combined analysis of MYC, HER2, CCND1 and PTEN aberrations suggested that aberrations of multiple PTEN/AKT pathway genes have a strong additive effect on breast cancer prognosis. While cancers with one of these aberrations behaved only marginally different from cancers with none, disease outcome was markedly worse in cancers with two or more aberrations as compared to those with only one aberration (p = 0.0002). In addition, the particularly poor prognosis of patients with HER2 amplification and PTEN deletions challenges the concept of PTEN deletions interfering with trastuzumab therapy.

Conclusion

PTEN deletion occurs in a relevant fraction of breast cancers, and is linked to aggressive tumor behavior. Reduced PTEN function cooperates with MYC and HER2 activation in conferring aggressive phenotype to cancer cells.
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Metadata
Title
Partial PTEN deletion is linked to poor prognosis in breast cancer
Authors
P. Lebok
V. Kopperschmidt
M. Kluth
C. Hube-Magg
C. Özden
Taskin B.
K. Hussein
A. Mittenzwei
A. Lebeau
I. Witzel
L. Wölber
S. Mahner
F. Jänicke
S. Geist
P. Paluchowski
C. Wilke
U. Heilenkötter
Ronald Simon
Guido Sauter
L. Terracciano
R. Krech
A. von d. Assen
V. Müller
E. Burandt
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1770-3

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