title: Prediction of spontaneous regression of cervical intraepithelial neoplasia lesions grades 2 and 3 by proteomic analysis.
abstract: Regression of cervical intraepithelial neoplasia (CIN) 2-3 to CIN 1 or less is associated with immune response as demonstrated by immunohistochemistry in formaldehyde-fixed paraffin-embedded (FFPE) biopsies. Proteomic analysis of water-soluble proteins in supernatants of biopsy samples with LC-MS (LTQ-Orbitrap) was used to identify proteins predictive of CIN2-3 lesions regression. CIN2-3 in the biopsies and persistence (CIN2-3) or regression (≤CIN1) in follow-up cone biopsies was validated histologically by two experienced pathologists. In a learning set of 20 CIN2-3 (10 regressions and 10 persistence cases), supernatants were depleted of seven high abundance proteins prior to unidimensional LC-MS/MS protein analysis. Mean protein concentration was 0.81 mg/mL (range: 0.55-1.14). Multivariate statistical methods were used to identify proteins that were able to discriminate between regressive and persistent CIN2-3. The findings were validated in an independent test set of 20 CIN2-3 (10 regressions and 10 persistence cases). Multistep identification criteria identified 165 proteins. In the learning set, zinc finger protein 441 and phospholipase D6 independently discriminated between regressive and persistent CIN2-3 lesions and correctly classified all 20 patients. Nine regression and all persistence cases were correctly classified in the validation set. Zinc finger protein 441 and phospholipase D6 in supernatant samples detected by LTQ-Orbitrap can predict regression of CIN2-3.
authors.affiliation: Norconsult AS, Section 355 QA Service, P.O. Box 216, NO-4503 Mandal, Norway ; Former International Research Institute of Stavanger (IRIS), P.O. Box 8046, 4068 Stavanger, Norway.
authors.forename: Kai-Erik
authors.initials: KE
authors.lastname: Uleberg
authors.affiliation: Pathology Department, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway.
authors.forename: Irene Tveiterås
authors.initials: IT
authors.lastname: Ovestad
authors.affiliation: Department of Gynecology and Obstetrics, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway.
authors.forename: Ane Cecilie
authors.initials: AC
authors.lastname: Munk
authors.affiliation: Department of Medical Biochemistry, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway.
authors.forename: Cato
authors.identifier: 0000-0003-2691-6052
authors.initials: C
authors.lastname: Brede
authors.affiliation: Pathology Department, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway.
authors.forename: Bianca
authors.initials: B
authors.lastname: van Diermen
authors.affiliation: Pathology Department, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway.
authors.forename: Einar
authors.initials: E
authors.lastname: Gudlaugsson
authors.affiliation: Pathology Department, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway.
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
authors.affiliation: Former International Research Institute of Stavanger (IRIS), P.O. Box 8046, 4068 Stavanger, Norway ; Mediteam AS, Sjøveien 34, 4315 Sandnes, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Hjelle
authors.affiliation: Pathology Department, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway ; The Gade Institute, University of Bergen, P.O. Box 1400, 5021 Bergen, Norway.
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Baak