Tag Archive for: epithelial–mesenchymal transition


Article of the week: “Twist” of fate: epithelial–mesenchymal transition (EMT) markers predict recurrence in prostate cancer

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Expression patterns of epithelial–mesenchymal transition markers in localized prostate cancer: significance in clinicopathological outcomes following radical prostatectomy

Hosny M. Behnsawy, Hideaki Miyake, Ken-Ichi Harada and Masato Fujisawa


• To analyse the expression patterns of multiple molecular markers implicated in epithelial–mesenchymal transition (EMT) in localized prostate cancer (PC), in order to clarify the significance of these markers in patients undergoing radical prostatectomy (RP).


• Expression levels of 13 EMT markers, namely E-cadherin, N-cadherin, b-catenin, g-catenin, fibronectin, matrix metalloproteinase (MMP) 2, MMP-9, Slug, Snail, Twist, vimentin, ZEB1 and ZEB2, in RP specimens from 197 consecutive patients with localized PC were evaluated by immunohistochemical staining.


• Of the 13 markers, expression levels of E-cadherin, Snail, Twist and vimentin were closely associated with several conventional prognostic factors.

• Univariate analysis identified these four EMT markers as significant predictors for biochemical recurrence (BR), while serum prostate-specific antigen, Gleason score, seminal vesicle invasion (SVI), surgical margin status (SMS) and tumour volume were also significant.

• Of these significant factors, expression levels of Twist and vimentin, SVI and SMS appeared to be independently related to BR on multivariate analysis

• There were significant differences in BR-free survival according to positive numbers of these four independent factors. That is, BR occurred in four of 90 patients who were negative for risk factors (4.4%), 21 of 83 positive for one or two risk factors (25.3%) and 19 of 24 positive for three or four risk factors (79.2%).


• Measurement of expression levels of potential EMT markers, particularly Twist and vimentin, in RP specimens, in addition to conventional prognostic parameters, would contribute to the accurate prediction of the biochemical outcome in patients with localized PC following RP.


Read Previous Articles of the Week

Editorial: The promise of EMT-associated biomarkers in a clinical setting

Emily A. Matuszak  and Natasha Kyprianou
Departments of Toxicology, Urology and Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA

Radical prostatectomy is among the most successful treatment modalities for patients exhibiting clinically localized prostate cancer. Despite this, roughly one-third of all radical prostatectomy patients will experience biochemical recurrence following prostatectomy. Curing prostate cancer requires a greater understanding of distinct biological events that differentiate prostate cancer from advanced life-threatening disease. Thus, a current challenge facing the clinical management of prostate cancer is the need for novel prognostic biomarkers capable of predicting biochemical recurrence to direct therapeutic interventions at earlier disease stages.

The oncogenic epithelial–mesenchymal transition (EMT) plays a critical role in metastatic prostate cancer progression [1]. EMTs engender coordinated molecular and genetic events which provoke phenotypic transformations that are indicative of the acquisition of mesenchymal characteristics which yield altered cellular behaviours [2]. Such altered behaviours may include but are not limited to enhanced migratory capability, increased invasive capacity, heightened resistance to apoptosis and conferred stem-like properties [3,4]. Conversion of an epithelial-derived prostate cancer cell to a more mesenchymal-like state has recently been implicated in prostate tumourigenesis as a mechanism facilitating the progression to metastatic castration-resistant disease [5].While alterations in the expression profiles of numerous EMT-associated transcriptional regulators and their molecular targets have served as biomarkers for studying EMT programmes, less is known about the contributions of EMTs in the emergence of treatment failure and tumour recurrence. Recently, EMT has been suggested to be a programme involved in metastatic disease progression that may also profoundly influence therapeutic outcomes amongst patients. Thus, it may be advantageous to develop predictors for risk assessment among prostate cancer patients that include specific EMT-associated markers in clinical evaluations.

Despite our current lack of knowledge regarding the clinicopathological significance of EMT, the potential value of an EMT marker signature as a prognostic indicator of biochemical recurrence among prostate cancer patients has emerged with some promise. Behnsawy et al. establish an initial path towards estimating the clinical value of assessing EMT marker levels in tandem with conventional clinicopathological prognostic factors in radical prostatectomy specimens from patients with organ confined prostate cancer, without any neoadjuvant therapy. Their evaluation follows a robust profile and results intriguingly reflect a pattern that may facilitate prediction of biochemical recurrence among patients. Using an exhaustive immunohistochemical analysis, the expression patterns of 13 EMT markers were evaluated in 197 radical prostatectomy specimens of which the expression levels of two EMT-associated markers, Twist and vimentin, were the most promising factors for such predictions.

The novel aspect and translational significance of this study are both reflected in the homogeneity of the patient population, in terms of localized organ confined disease. It represents an initial step towards recognizing an expression signature for specific EMT-associated factors in the therapeutic outcome of localized prostate cancer, but not disease progression. While the clinical impact of the reported findings may not be fully apparent, one may begin to speculate the promise of incorporating EMT-associated biomarkers in a clinical setting to facilitate diagnosis, prognosis and/or directing treatment strategies among patients. Primary endpoints of acquisition of an EMT phenotype following androgen axis targeting treatment must be clearly defined in the design of future clinical trials for the treatment of prostate cancer patients, with caution being given to selection of biopsy specimens vs radical prostatectomy specimens at an ‘optimal’ EMT window and in order to mitigate bias in tissue sampling resulting from long duration of therapeutic intervention. Control groups will provide valuable biological material to identify alternative mechanisms of treatment resistance (MAPK signalling). The statistical power in the relatively large cohort analysed enhances our confidence in considering the EMT landscape as an attractive platform for prediction of therapeutic response in future clinical trials. The concern, however, of whether improved prediction of biochemical recurrence by EMT profiling in pretreatment biopsies justifies its integration in the clinicopathological parameters (Gleason score, PSA) remains. Thus high expectations and much promise surround the pathological exploitation of EMT biomarkers (as signatures) in identifying profiles of tumour aggressiveness and providing a significant contribution in our quest towards the development of personalized therapies in prostate cancer patients with advanced disease.

1 Matuszak E, Kyprianou N. Androgen regulation of epithelial–mesenchymal transition in prostate tumorigenesis. Expert Rev Endo Metab 2011; 6: 469–82
2 Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial–mesenchymal transition in development and disease. Cell 2009; 139: 871–90
3 Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009; 9: 265–73
4 Kalluri R, Weinberg R. The basics of epithelial–mesenchymal transition. J Clin Invest 2009; 119: 1420–8
5 Tanaka H, Kono E, Tran CP et al. Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance. Nat Med 2010; 16: 1414–20

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