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

Authors


Correspondence: Hideaki Miyake, Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

e-mail: hideakimiyake@hotmail.com

Abstract

What's known on the subject? and What does the study add?

  • There have been few studies evaluating the prognostic value of epithelial–mesenchymal transition markers in prostate cancer; therefore the significance of these markers in the prognosis of patients with prostate cancer, particularly those with localized disease, remains largely unknown.
  • Consideration of the expression levels of potential epithelial–mesenchymal transition markers, particularly Twist and vimentin, in addition to conventional prognostic parameters would contribute to the prediction of biochemical recurrence after radical prostatectomy for localized prostate cancer.

Objective

  • 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).

Patients and Methods

  • Expression levels of 13 EMT markers, namely E-cadherin, N-cadherin, β-catenin, γ-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.

Results

  • 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%).

Conclusion

  • 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.

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