title: S100A7 (psoriasin) expression is associated with aggressive features and alteration of Jab1 in ductal carcinoma in situ of the breast.
abstract: BACKGROUND
  The S100A7 (psoriasin) gene is highly expressed in ductal carcinoma in situ (DCIS) of the breast and can be downregulated in invasive carcinoma. Persistent S100A7 expression in invasive carcinoma is associated with a worse prognosis, and this effect may be mediated in part through interaction with the multifunctional cell signaling protein Jab1.
  
  
  METHODS
  In order to investigate the relationship between S100A7 and progression from DCIS to invasive carcinoma, we studied S100A7 expression in 136 patients with DCIS (including 46 patients with associated invasive carcinoma) by immunohistochemistry.
  
  
  RESULTS
  S100A7 expression was present in 63 out of 136 (46%) of DCIS lesions and was associated with estrogen receptor negative status (P = 0.0002), higher nuclear grade (P < 0.0001), necrosis (P < 0.0001) and inflammation (P < 0.0001). S100A7 status was no different between DCIS with and DCIS without an invasive component, but higher levels of S100A7 were present in DCIS associated with invasive carcinoma (P < 0.004). Analysis of a subset of cases showed that S100A7 expression was also associated with an increase in nuclear Jab1 (n = 43; P = 0.0019) and reduced p27kip1 (n = 47; P = 0.0168). In cases of DCIS associated with invasive carcinoma, there was also a significant reduction in S100A7 between in situ and invasive components (n = 46; P < 0.0001). In pure DCIS cases treated by local excision, there was no difference in frequency of S100A7 expression between patients with recurrence of DCIS (n = 9) and those without (n = 36).
  
  
  CONCLUSIONS
  The findings reported here suggest that, although S100A7 may not be a marker for recurrence of DCIS, it is associated with poor prognostic markers in DCIS and may influence progression of breast carcinoma through its interaction with and influence on Jab1.
authors.affiliation: Manitoba Institute of Cell Biology and Department of Pathology, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada. umember0@cc.umanitoba.ca
authors.forename: Ethan D
authors.initials: ED
authors.lastname: Emberley
authors.forename: Salem
authors.initials: S
authors.lastname: Alowami
authors.forename: Linda
authors.initials: L
authors.lastname: Snell
authors.forename: Leigh C
authors.initials: LC
authors.lastname: Murphy
authors.forename: Peter H
authors.initials: PH
authors.lastname: Watson
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D000075686:COP9 Signalosome Complex; D002135:Calcium-Binding Proteins / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D010447:Peptide Hydrolases; D011960:Receptors, Estrogen / Q000096:biosynthesis; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011960:Receptors, Estrogen; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex