title: PI3K, Rac1 and pPAK1  are overexpressed in extramammary Paget's disease.
abstract: BACKGROUND
  Phosphatidylinositol 3-kinase (PI3K), Ras-related C3 botulinum toxin substrate 1 (Rac1) and P21-activated protein kinase 1 (PAK1) appear to play important roles in the pathogenesis of several tumors, but their expressions in extramammary Paget's disease (EMPD) have not been investigated yet.
  
  
  OBJECTIVE
  To investigate the potential contribution of the PI3K, Rac1 and PAK1 to the development of EMPD.
  
  
  METHODS
  Thirty-five paraffin-embedded EMPD specimens were subjected to immunohistochemical staining for PI3K (85α), Rac1 and pPAK1.
  
  
  RESULTS
  All the 35 primary EMPD specimens, including 20 non-invasive EMPD, 13 invasive EMPD and 2 metastatic lymph nodes, showed cytoplasm overexpression of PI3K (85α), Rac1 and pPAK1. The expression (% positive cells) of PI3K(85α), Rac1 and pPAK1 (90.1 ± 8.6, 91.4 ± 9.5 and 89.6 ± 10.8% ) in EMPD were significantly higher than in apocrine glands of normal skin ( 20.1 ± 11.9, 29.8 ± 8.9, 41.1 ± 13.4%), and the expression in invasive EMPD with lymph node metastasis (98.2 ± 1.7, 98.8 ± 0.7 and 98.4 ± 0.9%) are significantly higher than in invasive EMPD without lymph node metastasis (94.1 ± 2.6, 96.5 ± 1.7 and 95.3 ± 1.1%) and non-invasive EMPD (85.2 ± 8.4, 87.1 ± 9.9 and 83.1 ± 10.6%). There were significant positive correlations of the expression levels between PI3K (85α) and Rac1, as well as between Rac1 and pPAK1 in EMPD.
  
  
  CONCLUSIONS
  These results indicate that PI3K, Rac1 and PAK1 may play important roles in the pathogenesis of EMPD.
authors: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Yue
authors: Y
authors: Qian
authors: Na
authors: N
authors: Zhang
authors: Siyuan
authors: S
authors: Chen
authors: Shujuan
authors: S
authors: Chu
authors: Aiping
authors: A
authors: Feng
authors: Houjun
authors: H
authors: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010145:Paget Disease, Extramammary / Q000201:enzymology* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D054462:p21-Activated Kinases / Q000096:biosynthesis*; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis*
chemical_list: D009363:Neoplasm Proteins; C107953:RAC1 protein, human; D019869:Phosphatidylinositol 3-Kinases; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; D020830:rac1 GTP-Binding Protein