title: Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane staining and invasion in pituitary adenomas.
abstract: BACKGROUND
  Loss of the cell adhesion protein E-cadherin is associated with invasion and metastasis in a number of malignancies. Recent studies have highlighted that loss of E-cadherin cell membrane expression may be accompanied by its detection in the nucleus, suggesting cellular redistribution during neoplasia. Pituitary tumors, although typically benign, may be locally invasive, and loss of membranous E-cadherin has been reported as a marker of invasion in prolactinomas.
  
  
  OBJECTIVE
  Our objective was to study E-cadherin expression in pituitary adenomas, specifically whether nuclear redistribution occurs in this setting.
  
  
  METHODS
  Immunohistochemistry, RT-PCR, and direct sequencing were performed.
  
  
  RESULTS
  Strong cytoplasmic membrane staining was present in all eight normal samples but completely absent in 21 of 44 adenomas (48%) with weak staining in an additional 11 adenomas using an antibody against the extracellular domain of E-cadherin. To identify nuclear translocation of the protein, immunohistochemistry was performed using an antibody against the cytoplasmic domain. Nuclear staining was present in 38 of 44 adenomas (86%) and absent in normal tissue. Nuclear E-cadherin inversely correlated with loss of E-cadherin cytoplasmic membrane staining and was associated with tumor invasion (P = 0.009). To investigate the mechanism of nuclear redistribution of E-cadherin, we performed RT-PCR of mRNA and sequenced tumor DNA. E-cadherin mRNA expression was reduced in only one of 30 samples (3%). No mutations were detected.
  
  
  CONCLUSIONS
  E-cadherin was frequently lost at the cytoplasmic membrane but detected in the nucleus, suggesting that cleavage of the extracellular domain and nuclear translocation of E-cadherin is a common event that may determine local invasion in pituitary adenomas.
authors.affiliation: Cancer Genetics Unit, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia. marianne@med.usyd.edu.au
authors.forename: Marianne S
authors.initials: MS
authors.lastname: Elston
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.forename: John V
authors.initials: JV
authors.lastname: Conaglen
authors.forename: Adele
authors.initials: A
authors.lastname: Clarkson
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Cook
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Little
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Robinson
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Clifton-Bligh
authors.forename: Kerrie L
authors.initials: KL
authors.lastname: McDonald
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000235:genetics*; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010902:Pituitary Gland / Q000502:physiology; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D015175:Prolactinoma / Q000235:genetics* / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015820:Cadherins; D017931:DNA Primers; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm