Partial PTEN deletion is linked to poor prognosis in breast cancer
Autor: | M. Kluth, A. Mittenzwei, Ronald Simon, Patrick Lebok, Khakan Hussein, Volkmar Müller, Claudia Hube-Magg, Christian Wilke, Isabell Witzel, Uwe Heilenkötter, Fritz Jänicke, Annette Lebeau, V. Kopperschmidt, Luigi Terracciano, Stefan Geist, Cansu Özden, Sven Mahner, Billurvan Taskin, A von der Assen, Guido Sauter, Rainer Krech, E Burandt, Linn Wölber, Peter Paluchowski |
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Rok vydání: | 2015 |
Předmět: |
Oncology
Adult medicine.medical_specialty Cancer Research PTEN Phosphatase Locus (genetics) Breast Neoplasms In situ hybridization Breast cancer FISH Surgical oncology Internal medicine medicine Genetics Tensin Humans Clinical significance In Situ Hybridization Fluorescence Aged Aged 80 and over biology business.industry PTEN Phosphohydrolase Middle Aged medicine.disease Prognosis Tissue Array Analysis biology.protein Cancer research Female Chromosome Deletion business Research Article |
Zdroj: | BMC Cancer |
ISSN: | 1471-2407 |
Popis: | 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. |
Databáze: | OpenAIRE |
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