1700 - WNT-2, but not WNT-1 expression increases during tumorgenesis in breast, prostate, lung cancer and melanoma
|Date||28 September 2012|
|Event||ESMO Congress 2012|
|Topics|| Pathology/Molecular Biology
A. Stanczak1, A. Brozyna2, H. Wisniewska2, W. Jozwicki2, L. Bodnar3, M. Lamparska-Przybysz1, M. Wieczorek4
WNT/�-catenin pathway regulates cell cycle and proliferation. It is triggered by WNT ligands, and drives �-catenin regulated expression of cyclin D1, c-Myc, MMP7. Moreover �-catenin, along with E-cadherin, forms adherent junctions mediating cell adhesion. WNT-1 is a known oncogene and its expression occurs in several malignancies such as breast, prostate and lung cancers, while WNT-2 is less known member of WNT ligands family. The aim of our study was to investigate the expression of WNT-1, WNT-2, �-catenin, E-cadherin and cyclin D1 in melanoma, breast, lung, prostate cancer in comparison to adjacent normal tissue and to further understand WNT ligands significance as a potential biomarker. Formalin-fixed, paraffin-embedded samples were obtained from tumors and adjacent-normal tissues from 26 breast cancer patients, 22 non small cell lung cancers patients, 23 prostate cancers patients, 24 melanomas patients in I-III stage of the disease. Expression of WNT-1, WNT-2, �-catenin, E-cadherin and cyclin D1 was assessed by immunohistochemistry and analyzed by two independent histopathologists. Changes of studied proteins expression profiles between normal and malignant tissues were measured with Wilcoxon test, while comparison of expression of analyzed proteins between tumors was performed with Kruskall-Wallis and post hoc test. A value of p < 0,05 was considered significant. The study received approval by the Local Bioethics Committee. In our study, WNT-1 cytoplasmic expression was increased in breast cancer (p = 0,003) and melanoma (p = 0,0001), while in lung cancer it was decreased (p = 0,002). WNT-2 cytoplasmic expression was increased in breast (p < 0,0001), prostate cancer (p = 0,0002), melanoma (p = 0,0007), while in lung cancer WNT-2 increased expression showed a trend towards significance (p = 0,06). Moreover WNT-2 ligand was found in cell nuclei in all tumors and its expression level was increased in breast cancer (p = 0,007) and decreased in melanoma (p = 0,042). Our study revealed that WNT-2, but not WNT-1 expression was increased in all analyzed tumors. Moreover WNT-2 ligand was detected in cell nuclei, what could implicated its yet undiscovered role in gene expression regulation.Disclosure
M. Wieczorek: Maciej Wieczorek is Chief Executive Officer of Celon Pharma Ltd.
All other authors have declared no conflicts of interest.