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      Loss of PTEN expression in breast cancer: association with clinicopathological characteristics and prognosis

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          Abstract

          Various studies have evaluated the significance of PTEN (phosphatase and tensin homolog deleted from chromosome 10) expression in breast cancer, but their results remain controversial. We conducted a meta-analysis to evaluate the associations of PTEN expression with clinicopathological characteristics and prognosis in breast cancer. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to identify relevant publications. The associations between PTEN expression and clinicopathological parameters, disease-free survival (DFS), and overall survival (OS) were then assessed via meta-analyses of odds ratio (ORs) and hazard ratio (HRs) with 95% confidence intervals (CIs). Based on 27 studies involving 10,231 patients, the pooled results revealed that PTEN loss was significantly more common in breast cancer than in normal tissues (OR = 12.15, 95% CI = 6.48–22.79, P < 0.00001) and that PTEN loss had clear associations with larger tumor size (> 2 cm, OR = 0.62, 95% CI = 0.48–0.82, P = 0.0006), lymph node metastasis(OR = 0.61, 95% CI = 0.45–0.82, P = 0.0001), later TNM stage(stage III–IV, OR = 0.55, 95% CI = 0.35–0.86, P = 0.009), poor differentiation(OR = 0.37, 95% CI = 0.24–0.59, P < 0.0001), and the highly aggressive triple-negative phenotype (OR = 1.62, 95% CI = 1.23–2.12, P = 0.0005). Moreover, patients with PTEN loss exhibited significantly worse DFS and OS(HR = 1.63, 95% CI = 1.04–2.22, P < 0.00001; HR = 1.41, 95% CI = 1.08–1.73, P < 0.0001; respectively). In conclusion, PTEN loss might predict more aggressive behavior and worse outcomes in patients with breast cancer.

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          Most cited references42

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          (O.) Andersen, (D.T.T.) Haug (edd.) Relative Chronology in Early Greek Epic Poetry. Pp. xiv + 277, figs. Cambridge: Cambridge University Press, 2012. Cased, £60, US$99. ISBN: 978-0-521-19497-6.

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            Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer.

            The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene is often altered in prostate cancer. To determine the prevalence and clinical significance of the different mechanisms of PTEN inactivation, we analyzed PTEN deletions in TMAs containing 4699 hormone-naïve and 57 hormone-refractory prostate cancers using fluorescence in situ hybridization analysis. PTEN mutations and methylation were analyzed in subsets of 149 and 34 tumors, respectively. PTEN deletions were present in 20.2% (458/2266) of prostate cancers, including 8.1% heterozygous and 12.1% homozygous deletions, and were linked to advanced tumor stage (P < 0.0001), high Gleason grade (P < 0.0001), presence of lymph node metastasis (P = 0.0002), hormone-refractory disease (P < 0.0001), presence of ERG gene fusion (P < 0.0001), and nuclear p53 accumulation (P < 0.0001). PTEN deletions were also associated with early prostate-specific antigen recurrence in univariate (P < 0.0001) and multivariate (P = 0.0158) analyses. The prognostic impact of PTEN deletion was seen in both ERG fusion-positive and ERG fusion-negative tumors. PTEN mutations were found in 4 (12.9%) of 31 cancers with heterozygous PTEN deletions but in only 1 (2%) of 59 cancers without PTEN deletion (P = 0.027). Aberrant PTEN promoter methylation was not detected in 34 tumors. The results of this study demonstrate that biallelic PTEN inactivation, by either homozygous deletion or deletion of one allele and mutation of the other, occurs in most PTEN-defective cancers and characterizes a particularly aggressive subset of metastatic and hormone-refractory prostate cancers. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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              Akt-regulated pathways in prostate cancer.

              Prostate cancer remains a major cause of cancer-related mortality. Genetic clues to the molecular pathways driving the most aggressive forms of prostate cancer have been limited. Genetic inactivation of PTEN through either gene deletion or point mutation is reasonably common in metastatic prostate cancer and the resulting activation of phosphoinostide 3-kinase, AKT and mTOR provides a major therapeutic opportunity in this disease as mTOR inhibitors, HSP90 inhibitors and PI3K inhibitors begin to enter clinical development.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                9 May 2017
                31 March 2017
                : 8
                : 19
                : 32043-32054
                Affiliations
                1 Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
                2 Institute of Endemic Diseases, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, P.R. China
                3 Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, P.R. China
                Author notes
                Correspondence to: Jin Yang, 1473106133@ 123456qq.com
                Article
                16761
                10.18632/oncotarget.16761
                5458267
                28410191
                7a5ca2de-2e43-4cee-b578-33e9d261ce06
                Copyright: © 2017 Li et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 January 2017
                : 22 March 2017
                Categories
                Research Paper

                Oncology & Radiotherapy
                pten,breast cancer,prognosis,meta-analysis
                Oncology & Radiotherapy
                pten, breast cancer, prognosis, meta-analysis

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