Patterns of N-cadherin (N-cad) and vimentin (Vim) expression as a sign of epithelial-mesenchymal transition (EMT) in prostate cancer (PCa)

Abstract

Abstract Background EMT is a mechanism of metastatic spread and therapy resistance. Agents targeting mesenchymal markers up-regulated during EMT, like N-cad (ADH-1, biflorin, synthetic peptide H-SWTLYTPSGQSK-NH2, mAbs) and Vim (withaferin-A, FiVe1, simvastatin, DNA aptamer NAS-24, mAbs) have shown promising results in preclinical studies. Aim: to evaluate the expression of N-cad and Vim in PCa. Methods PCa samples from 48 patients were stained immunohistochemically on consequent sections with rabbit polyclonal antibodies (ThermoScientific) to N-cad (1:5000) and Vim (1:1000). Staining was evaluated semiquantitavely (% of stained cells and intensity of staining), membranous (M) and cytoplasmic (CP) separately. Results Expression patterns of both markers had similarities: 1) both M and CP expression was seen; 2) expression was present in both PCa (94,4% for N-cad) and non-cancerous glands (NCG) (due to staining artifacts CP N-cad couldn’t be reliably evaluated); 3) staining was patchy (especially for N-cad, while Vim showed rather diffuse CP staining in some cases), with positive and negative cells present within one gland; 4) no special characteristics of staining were seen in different histological structures, areas of perineural or extracapsular invasion; 5) no significant correlations were found between markers’ expression and Gleason score, Gleason grading group, the extent of local spread. In PCa M staining predominated for N-cad, while CP for Vim, according to their normal subcellular distribution. Staining pattern in NCG was similar in different cases, but PCa showed variable patterns of staining. M Vim was absent in 30.6% of PCa cases. In NCG, conversely, M Vim was more prevalent. It couldn’t be assessed whether both markers were present in the same or different cells, but N-cad-high (>5% M+ cells) PCa tended to have higher M and CP Vim. It may be due to a small sample size or different mechanisms of mesenchymal markers upregulation during EMT. Moderate correlations were seen between M and CP Vim (p Conclusions N-cad and/or Vim neoexpression is present in most PCa samples and it suggests that agents, targeting these molecules, should be further studied as possible new therapeutics in PCa. Legal entity responsible for the study M. Puchinskaya. Funding Belarusian Republican Foundation for Fundamental Research. Disclosure The author has declared no conflicts of interest.