CTHRC1, periostin and versican in the progression of prostate cancer

Background:

We have previously reported collagen triple helix repeat containing 1 (CTHRC1) as breast cancer related protein (Turashvili et al 2007) and its potent role in breast cancer bone metastases in combination with periostin (Kharaishvili et al 2011). CTHRC1 has been shown to affect Wnt signaling, collagen deposition and bone formation and generally belongs to extracellular matrix proteins which are abnormally expressed in tumor microenvironment. CTHRC1 has not been studied in prostate cancer yet. We decided to verify its expression in our patients set together with periostin and versican and other relevant proteins.

Material and methods:

Formalin fixed paraffin embedded tissues of 101 prostate carcinomas (PCa) and 32 benign (BPH) cases were stained immunohistochemically for CTHRC1, periostin, versican, E-cadherin and beta-catenin, and scored. Carcinomas were classified into localized and advanced groups. Statistical analysis was performed by SPSS software.

Results:

CTHRC1 was predominantly localized in cancer cell cytoplasm and extracellular matrix, while versican and periostin were rarely positive in cancer cells. All three proteins were expressed in the stroma surrounding cancer. Expression of all markers was significantly higher in PCa in comparison to BPH (CTHRC1 in cancer epithelium and stroma, periostin in stroma, all p<0.001, versican in stroma p=0.036), and also higher in advanced cases in comparison to localized ones (CTHRC1 epithelial p=0.002; periostin stromal p=0.001; versican stromal p<0.001).

CTHRC1 stromal and epithelial expression significantly correlated with periostin stomal positivity (r=0.232, p=0.008 and r=0.235, p=0.007, respectively). Versican and periostin stromal expressions were also in association (r=0.438, p<0.001). These two proteins showed similar tissue expression patterns. Periostin inversely correlated with membranous beta-catenin and E-cadherin (r=-0.4 and -0.367, respectively, both p<0.001). CTHRC1 also showed negative correlation with E-cadherin (r=0.188, p=0.03).

Conclusions:

We showed that CHTRC1, periostin and versican are prostate cancer related proteins and are expressed in cancer cells and epithelial-mesenchymal interface. In the performed study their significant increase in prostate cancer tissue demonstrate that mentioned proteins play a role in the progression of prostate cancer.

Acknowledgements: The study was supported in part by grant NT13573 from the Czech Ministry of Health and EU infrastructure support CZ.1.05/2.1.00/01.0030