title: End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.
abstract: BACKGROUND
  Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and despite the improvement in treatment strategy, 5-year survival rates are about 50%. Identification of patients at high risk of recurrence may enable rigorous personalized post-treatment management. In an earlier proteomics study we observed overexpression of End Binding Protein (EB1) in OSCC. In the present study we investigated the diagnostic and prognostic significance of alterations in expression of EB1 in oral cancer.
  
  
  METHODS
  In this retrospective study, the expression of EB1 protein was evaluated in 259 OSCCs, 41 dysplasia, 166 hyperplasia and 126 normal tissues using immunohistochemistry and correlated with clinical-pathological parameters and prognosis of OSCC patients over a follow-up period of up to 91months.
  
  
  RESULTS
  Significantly higher expression of cytoplasmic EB1 was observed in hyperplasia [p<0.001, OR=7.2, 95% CI=4.1-12.8], dysplasia (p<0.001, OR=21.8, CI=8.8-50.2) and OSCCs (p<0.001, OR=10.1, CI=5.8-17.4) in comparison with normal mucosa. Univariate analysis revealed cytoplasmic EB1 association with tumor grade, tumor size and recurrence of the disease. Kaplan Meier survival analysis of EB1 expression showed significantly reduced disease free survival (DFS) (p=0.003). Notably, OSCC patients showing cytoplasmic EB1 overexpression demonstrated significantly reduced DFS (p=0.004, HR=2.1).
  
  
  CONCLUSIONS
  EB1 overexpression is an early event in oral tumorigenesis and cytoplasmic EB1 accumulation is associated with poor prognosis and tumor recurrence in OSCC patients.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Mehra
authors.affiliation: Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Alok
authors.initials: A
authors.lastname: Thakar
authors.affiliation: Department of Surgery, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Nootan Kumar
authors.initials: NK
authors.lastname: Shukla
authors.affiliation: Department of Dental Surgery, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ajoy
authors.initials: A
authors.lastname: Roychoudhary
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Mehar Chand
authors.initials: MC
authors.lastname: Sharma
authors.affiliation: Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada; Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology - Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Ontario, Canada. Electronic address: rralhan@mtsinai.on.ca.
authors.forename: Ranju
authors.initials: R
authors.lastname: Ralhan
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. Electronic address: s_s_chauhan@hotmail.com.
authors.forename: Shyam Singh
authors.initials: SS
authors.lastname: Chauhan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology*; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins
keywords: Dysplasia; EB1; Oral cancer; Prognosis