Partial PTEN deletion is linked to poor prognosis in breast cancer. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Lebok, P.; Kopperschmidt, V.; Kluth, M.; Hube-Magg, C.; Özden, C.; B., Taskin; Hussein, K.; Mittenzwei, A.; Lebeau, A.; Witzel, I.; Wölber, L.; Mahner, S.; Jänicke, F.; Geist, S.; Paluchowski, P.; Wilke, C.; Heilenkötter, U.; Simon, Ronald; Sauter, Guido; Terracciano, L.; Krech, R.; von d. Assen, A.; Müller, V.; Burandt, E.
• Is Part Of: BMC cancer. Volume 15:Issue 1(2015)
• Page Start: 1
• Page End: 10
• Publication Date: 2015-12
• Subjects: Breast cancer -- PTEN -- FISH -- Prognosis; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s12885-015-1770-3
• Languages: English
• ISSNs: 1471-2407

Abstract

Abstract Background Deletions of chromosome 10q23, including thePTEN (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 aPTEN -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, andCCND1 amplification;p = 0.0020).PTEN deletions were also strongly linked to amplification of genes involved in the PTEN/AKT pathway such asMYC (p = 0.0430) andHER2 (p = 0.0065). Remarkably the combined analysis ofMYC, HER2, CCND1 andPTEN 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 withHER2 amplification andPTEN deletions challenges the concept ofPTEN deletions interfering with trastuzumab therapy. Conclusion PTEN deletion occurs in a relevant fraction of breast cancers, and is linked to aggressive tumor behavior. ReducedPTEN function cooperates withMYC andHER2 activation in conferring aggressive phenotype to cancer cells.