title: Loss of Wnt-5α is associated with an invasive phenotype of extramammary Paget's disease.
abstract: BACKGROUND
  The Wnt (wingless-type MMTV integration site) gene family encodes secretory signaling molecules that play a diverse biological role in the regulation of normal and pathological processes, including cell growth, differentiation and oncogenesis. However, the role of Wnt genes in the development of extramammary Paget's disease remains unknown.
  
  
  OBJECTIVE
  To investigate the expression of Wnt-1, Wnt-5α and their downstream genes, β-catenin and c-Myc, in extramammary Paget's disease.
  
  
  METHODS
  Paraffin-embedded specimens of extramammary Paget's disease (33 specimens from 22 patients), including 7 specimens with dermal invasion and 4 with lymph node metastasis, were examined immunohistochemically for Wnt-1, Wnt-5α, β-catenin and c-Myc. Seven normal genital skin specimens served as controls.
  
  
  RESULTS
  The expression levels of Wnt-1 and β-catenin in extramammary Paget's disease were significantly correlated with each other; however, their expression levels in the invasive extramammary Paget's disease were similar to those of wholly intraepithelial extramammary Paget's disease. Nuclear expression of c-Myc was significantly higher in the invasive extramammary Paget's disease in comparison with intraepithelial extramammary Paget's disease. Interestingly, the expression of Wnt-5α in invasive extramammary Paget's disease was significantly downregulated compared to wholly intraepithelial extramammary Paget's disease.
  
  
  CONCLUSIONS
  The Wnt-1/β-catenin pathway may not play an important role in the progression of extramammary Paget's disease. The loss of Wnt-5α, however, may play a role in the invasiveness of extramammary Paget's disease.
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. lining@dermatol.med.kyushu-u.ac.jp
authors.forename: Lining
authors.initials: L
authors.lastname: Xie
authors.forename: Sayaka
authors.initials: S
authors.lastname: Hayashida
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
mesh_terms: D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010145:Paget Disease, Extramammary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D051153:Wnt Proteins / Q000096:biosynthesis* / Q000235:genetics; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein / Q000096:biosynthesis / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: C489427:MYC protein, human; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; D051176:beta Catenin