title: A protein profile study to discriminate CIN lesions from normal cervical epithelium.
abstract: BACKGROUND
  Cervical intraepithelial neoplasia (CIN), a frequently encountered disease caused by Human Papilloma Virus (HPV) is often diagnosed in formaldehyde-fixed paraffin embedded (FFPE) punch biopsies. Since it is known that this procedure strongly affects the water-soluble proteins contained in the cervical tissue we decided to investigate whether a water-soluble protein-saving biopsy processing method can be used to support the diagnosis of normal and CIN.
  
  
  METHODS
  Cervical punch biopsies from 55 women were incubated for 24 h at 4°C in RPMI1640 medium for protein analysis prior to usual FFPE processing and p16 and Ki67-supported histologic consensus diagnosis was assessed. The biopsy supernatants were subjected to surface-enhanced laser desorption-ionization time of flight mass spectrometry (SELDI-TOF MS) for identifying differentially expressed proteins. Binary logistic regression and classification and regression trees (CART) were used to develop a classification model.
  
  
  RESULTS
  The age of the patients ranged from 26 to 40 years (median 29.7). The consensus diagnoses were normal cervical tissue (n = 10) and CIN2-3 (n = 45). The mean protein concentration was 1.00 and 1.09 mg/ml in the normal and CIN2-3 group, respectively. The peak detection and clustering process resulted in 40 protein peaks. Many of these peaks differed between the two groups, but only three had independent discriminating power. The overall classification results were 88%.
  
  
  CONCLUSIONS
  Water-soluble proteins sampled from punch biopsies are promising to assist the diagnosis of normal and CIN2-3.
authors.affiliation: Pathology Department, Stavanger University Hospital, Armauer Hansen Road 20, PO Box 8100, 4068 Stavanger, Norway.
authors.forename: Kai-Erik
authors.initials: KE
authors.lastname: Uleberg
authors.forename: Ane Cecilie
authors.initials: AC
authors.lastname: Munk
authors.forename: Ivar
authors.initials: I
authors.lastname: Skaland
authors.forename: Cristina
authors.initials: C
authors.lastname: Furlan
authors.forename: Bianca
authors.initials: B
authors.lastname: van Diermen
authors.forename: Einar
authors.initials: E
authors.lastname: Gudlaugsson
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
authors.forename: Anais
authors.initials: A
authors.lastname: Malpica
authors.forename: Weiwei
authors.initials: W
authors.lastname: Feng
authors.forename: Anne
authors.initials: A
authors.lastname: Hjelle
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Baak
mesh_terms: D000328:Adult; D001706:Biopsy; D002584:Cervix Uteri / Q000378:metabolism* / Q000473:pathology*; D016001:Confidence Intervals; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology*
chemical_list: D009363:Neoplasm Proteins