title: Nuclear Ep-ICD expression is a predictor of poor prognosis in "low risk" prostate adenocarcinomas.
abstract: BACKGROUND
  Molecular markers for predicting prostate cancer (PCa) that would have poor prognosis are urgently needed for a more personalized treatment for patients. Regulated intramembrane proteolysis of Epithelial cell adhesion molecule results in shedding of the extracellular domain (EpEx) and release of its intracellular domain (Ep-ICD) which triggers oncogenic signaling and might correlate to tumor aggressiveness. This study aimed to explore the potential of Ep-ICD and EpEx to identify PCa that have poor prognosis.
  
  
  METHODS
  Immunohistochemical analysis of Ep-ICD and EpEx was carried out in normal prostate tissues (n = 100), benign prostate hyperplasia (BPH, n = 83), and prostate cancer (n = 249) using domain specific antibodies. The expression of Ep-ICD and EpEx was correlated with clinico- pathological parameters and disease free survival (DFS).
  
  
  RESULTS
  Reduced expression of nuclear Ep-ICD and membrane EpEx was observed in PCa in comparison with BPH and normal prostate tissues (p = 0.006, p < 0.001 respectively). For patients who had PCa with Gleason Score less than 7, preserved nuclear Ep-ICD emerged as the most significant marker in multivariate analysis for prolonged DFS, where these patients did not have recurrence during follow up of up to 12 years (p = 0.001).
  
  
  CONCLUSIONS
  Reduced expression of nuclear Ep-ICD was associated with shorter disease free survival in patients with a Gleason Score less than 7 and may be useful in identifying patients likely to have aggressive tumors with poor prognosis. Furthermore, nuclear Ep-ICD can differentiate between normal and prostate cancer tissues for ambiguous cases.
authors.affiliation: Alex and Simona Shnaider Laboratory in Molecular Oncology, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada.
authors.forename: Jasmeet
authors.initials: J
authors.lastname: Assi
authors.affiliation: Alex and Simona Shnaider Laboratory in Molecular Oncology, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Srivastava
authors.affiliation: Alex and Simona Shnaider Laboratory in Molecular Oncology, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada.
authors.forename: Ajay
authors.initials: A
authors.lastname: Matta
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: MacMillan
authors.affiliation: Alex and Simona Shnaider Laboratory in Molecular Oncology, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ranju
authors.initials: R
authors.lastname: Ralhan
authors.affiliation: Alex and Simona Shnaider Laboratory in Molecular Oncology, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada; Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Walfish
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D011379:Prognosis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology*
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule