Abstract A59: Prognostic relevance of PTEN and TP53 deletion in breast cancer

Abstract

Abstract Inactivation of PTEN and TP53 have been suggested to promote unfavorable phenotypes in various cancers, including breast cancer. Chromosomal deletion is one well established mechanism for inactivation of these genes. In breast cancer, deletions of TP53 and PTEN are known to occur, but systematic analyses of its clinical relevance are lacking. We thus analyzed a tissue microarray (TMA) with 2,197 breast cancers by fluorescence in-situ hybridization (FISH) using specific probes against TP53 and PTEN in combination with respective centromere probes. We found, that TP53 deletion (29%/1026 cancers) occur more frequent in breast cancers than deletions of PTEN (19%/1,239 cancers). The frequency of PTEN deletion varied between histological subtypes with highest deletion rate in medullary cancers (18 of 39, 46%) and lowest deletion rate in mucinous cancers (1 of 28; 3%; p<0.0001) for mucinous vs. medullary). PTEN deletions were significantly linked to various unfavorable tumor features, including 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). Deletions of TP53 were significantly linked to high-grade (p<0.0001) and high tumor cell proliferation (p=0,0193) but unrelated to histological subtypes, tumor stage, nodal status, and patient survival. Deletion of PTEN and TP53 were unrelated to each other (p=0.6469). Combined analysis of PTEN and TP53 deletions showed that TP53 deletion had no additional effect on patient prognosis in cancers with or without PTEN deletion. In conclusion, our data support a role of PTEN and TP53 deletions in breast cancer. However, only PTEN deletion is inked to aggressive tumor behavior, while TP53 deletion has no prognostic relevance in breast cancer. Citation Format: Martina Kluth, Anette Lebeau, Isabell Witzel, Sven Mahner, Linn Woelber, Stefan Geist, Peter Paluchowski, Christian Wilke, Uwe Heilenkoetter, Volkmar Mueller, Ronald Simon, Guido Sauter, Luigi Terracciano, Rainer Krech, Albert von der Assen, Eike Burandt, Patrick Lebok. Prognostic relevance of PTEN and TP53 deletion in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A59.