title: Targets of Wnt/ß-catenin transcription in penile carcinoma.
abstract: 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.
authors.affiliation: Division of Surgery, University College Hospital, London, United Kingdom and The Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
authors.forename: Manit
authors.initials: M
authors.lastname: Arya
authors.affiliation: Research Department of Cell and Developmental Biology, The Centre for Cell and Molecular Dynamics, Rockefeller Building, University College London, London, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Thrasivoulou
authors.affiliation: Department of Pathology, Portuguese Oncology Institute and Department of Pathology and Molecular Immunology, Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.affiliation: Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Millar
authors.affiliation: Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Hamblin
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: Reena
authors.initials: R
authors.lastname: Davda
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: Kristina
authors.initials: K
authors.lastname: Aare
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: John R
authors.initials: JR
authors.lastname: Masters
authors.affiliation: Dundee Imaging Facility, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Calum
authors.initials: C
authors.lastname: Thomson
authors.affiliation: Department of Urology, University College Hospital, London, United Kingdom.
authors.forename: Asif
authors.initials: A
authors.lastname: Muneer
authors.affiliation: Division of Surgery, Oncology, Urology and Women's Health, University Hospital of Northern Norway, Tromso, Norway.
authors.forename: Hitendra R H
authors.initials: HR
authors.lastname: Patel
authors.affiliation: Prostate Cancer Research Centre, Division of Surgery, University College London, London, United Kingdom.
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmed
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism*; D016022:Case-Control Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000378:metabolism; D010412:Penile Neoplasms / Q000235:genetics* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D014158:Transcription, Genetic; D060528:Wnt4 Protein / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; C555581:WNT4 protein, human; D060528:Wnt4 Protein; D051176:beta Catenin; D020783:Matrix Metalloproteinase 7