Reduced PTEN Expression Is Associated With Poor Outcome and Angiogenesis in Invasive Ductal Carcinoma of the Breast

Abstract

Loss of PTEN expression has been associated with advanced stages of tumor. Tumor angiogenesis is involved in tumor progression. In breast cancer, a high frequency of mutations of the PTEN locus has been reported. However, the prognostic importance of PTEN expression and its correlation with angiogenesis in breast cancer have not been well established. Formalin-fixed, paraffin-embedded tissues from 99 women with a primary diagnosis of invasive ductal carcinoma were evaluated for PTEN expression by immunohistochemical methods. The microvessel density (MVD) was also studied by immunohistochemical labeling of endothelial cells with CD34 antibody. Computerized image analysis was used to evaluate MVD. Reduced PTEN expression was seen in 27.3% of invasive ductal carcinoma. The MVD ranged from 22.0 to 197.0, with a median value of 58.5 (65.4 +/- 27.9). Reduced PTEN expression correlated with lymph node status (P < 0.01), tumor grade (P < 0.05), and tumor-node-metastasis (TNM) stage (P < 0.05). There was a statistically significant correlation between reduced PTEN expression and increased MVD (P < 0.05). The mean MVD was higher in reduced PTEN-expressive tumors, irrespective of stage, compared with normal PTEN-expressive tumors with the same stage. On multivariate analysis, only TNM stage and reduced PTEN expression correlated with survival. Our results suggest that reduced PTEN expression may be an independent prognostic indicator in patients with invasive ductal carcinoma. PTEN loss may be associated with increased tumor angiogenesis.

Phosphorylated S6 Kinase-1 as Predictive Marker of Lapatinib Efficacy in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients

“…Loss of PTEN expression results in activation of PI3K pathway leading to development of cancer [15,41]. PTEN loss is present in about one third of breast cancer patients, ranging from 15% to 48% [43][44][45][46]. Our study showed that the incidence of PTEN loss was 31.6%, which is consistent with other reported results.…”

Clinical significance of miR-21 expression in breast cancer: SYBR-Green I-based real-time RT-PCR study of invasive ductal carcinoma

“…However, the relationship between miR-21 and PTEN in breast cancer is not known. There is evidence that reduced expression of PTEN is associated with tumor progression and poor outcome in breast cancer (11,32,33), but the mechanism of PTEN down-regulation in breast cancer is not clear. Some studies found that the incidence of loss of heterozygosity (LOH) in PTEN was approximately 40% in breast cancer (34,35), but a further study showed that this level of LOH is not sufficient to reduce the expression of PTEN (32).…”

“…There are many reports that PTEN has an important role in tumorigenesis of breast cancer (6)(7)(8)(9). It has been shown that reduced PTEN expression is associated with lymph node metastasis, estrogen receptor status, tumor grade, tumor-nodemetastasis (TNM) stage, and microvessel density (MVD), and it may be a valuable prognostic marker in breast cancer (10,11). So, it is reasonable to propose that miR-21 regulating PTEN expression is a ubiquitous mechanism in solid tumors, including breast cancer.…”

Suppression of PTEN function increases breast cancer chemotherapeutic drug resistance while conferring sensitivity to mTOR inhibitors

“…Diverse mechanisms regulate PTEN expression (Lee et al, 2004;Tsutsui et al, 2005a, b;Abdel-Rahman et al, 2006;Agrawal and Eng, 2006). These range from gene deletion, alterations in mRNA splicing, subcellular localization or epigenetic mechanisms that prevent PTEN transcription.…”