| Autor: |
Arya M; Division of Surgery, University College Hospital, London, United Kingdom and The Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Thrasivoulou C; Research Department of Cell and Developmental Biology, The Centre for Cell and Molecular Dynamics, Rockefeller Building, University College London, London, United Kingdom., Henrique R; Department of Pathology, Portuguese Oncology Institute and Department of Pathology and Molecular Immunology, Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal., Millar M; Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Hamblin R; Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Davda R; Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom., Aare K; Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom., Masters JR; Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom., Thomson C; Dundee Imaging Facility, College of Life Sciences, University of Dundee, Dundee, United Kingdom., Muneer A; Department of Urology, University College Hospital, London, United Kingdom., Patel HR; Division of Surgery, Oncology, Urology and Women's Health, University Hospital of Northern Norway, Tromso, Norway., Ahmed A; Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom. |
| Abstrakt: |
Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p<0.01). Expression of all proteins, except CD1, showed a significant decrease in grade II compared to grade I tumors. High magnification, deconvolved confocal images were used to measure differences in co-localization between the four proteins. Significant (p<0.04-0.0001) differences were observed for various permutations of the combinations of proteins and state of the tissue (control, tumor grades I and II). Wnt signaling may play an important role in PeCa and proteins of the Wnt signaling network could be useful targets for diagnosis and prognostic stratification of disease. |
