title: A Selective Biomarker Panel Increases the Reproducibility and the Accuracy in Endometrial Biopsy Diagnosis.
abstract: Grading and histologic typing of endometrial cancer in biopsy material has a direct impact on the decision to perform lymphadenectomy and/or omentectomy in many cancer centers. Endometrial biopsies are among the most common general surgical pathology specimens. Multiple studies have shown that biopsy diagnosis suffers from a lack of reproducibility. Although many biomarkers have been proposed, none have been demonstrated to improve the diagnosis in the biopsy setting. In this study, 70 biopsies with endometrial carcinoma were supplemented with a biomarker panel consisting of ER, PR, P53, and DNA ploidy. A representative H&E slide was scanned digitally and made available to 12 gynecologic pathologists in 4 Nordic countries: Finland, Denmark, Sweden, and Norway. Reviewers diagnosed the cases both before and after being provided with the biomarker results. The interobserver percent agreement and Cohen κ improved from 75.8% (κ=0.52, moderate) to 84% (κ=0.68, substantial) with inclusion of the biomarker panel. Agreement with the subsequent hysterectomy diagnosis also improved from 83.6% (κ=0.67) to 88.7% (κ=0.77). There was no statistical improvement between a reflex (84% agreement) and a reflective testing algorithm (82.9% agreement), suggesting that the selective use of biomarkers is appropriate. Difficult cases were almost exclusively high-grade tumors. Finally, a statistical model indicated that only P53 and DNA ploidy, in conjunction with an H&E review, had an impact on the decision to upgrade or downgrade cases.
authors.affiliation: Department of Pathology and Cytology and Institution for Oncology-Pathology (D.N., E.S., J.W.C), Karolinska University Hospital and Karolinska Institutet, Stockholm Equalis (K.-L.W.) Statsoft AB (J.S.), Uppsala Department of Pathology (A.M.), Lund University Hospital, Lund Department of Pathology (C.M.), Sahlgrenska University Hospital, Gothenburg Department of Pathology (J.B.), Linköping University Hospital, Linköping, Sweden Department of Public Health and General Practice (M.V.), Norwegian University of Science and Technology Department of Pathology and Medical Genetics (A.B.A.), St Olavs Hospital, Trondheim University Hospital, Trondheim Department of Pathology (B.D.), Oslo University Hospital, Norwegian Radium Hospital, and Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo Department of Pathology (B.I.B.), Haukeland University Hospital, Bergen, Norway Department of Pathology (M.L.), Herlev University Hospital, Herlev Department of Pathology (A.G.), Aalborg University Hospital, Aalborg, Denmark Department of Pathology (A.L., E.L.-B.), Oulu University Hospital, Oulu Department of Pathology (O.C.), University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Denis
authors.initials: D
authors.lastname: Nastic
authors.forename: Emma
authors.initials: E
authors.lastname: Shanwell
authors.forename: Keng-Ling
authors.initials: KL
authors.lastname: Wallin
authors.forename: Marit
authors.initials: M
authors.lastname: Valla
authors.forename: Anna
authors.initials: A
authors.lastname: Måsbäck
authors.forename: Claudia
authors.initials: C
authors.lastname: Mateoiu
authors.forename: Marianne
authors.initials: M
authors.lastname: Lidang
authors.forename: Annikki
authors.initials: A
authors.lastname: Liakka
authors.forename: Elisa
authors.initials: E
authors.lastname: Lappi-Blanco
authors.forename: Anni
authors.initials: A
authors.lastname: Grove
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.forename: Olli
authors.initials: O
authors.lastname: Carpen
authors.forename: Bjørn I
authors.initials: BI
authors.lastname: Bertelsen
authors.forename: Julia
authors.initials: J
authors.lastname: Bak
authors.forename: Anne B
authors.initials: AB
authors.lastname: Abusland
authors.forename: Jonas
authors.initials: J
authors.lastname: Selling
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Carlson
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D001706:Biopsy; D004247:DNA / Q000032:analysis; D016889:Endometrial Neoplasms / Q000145:classification / Q000473:pathology*; D004717:Endometrium / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D011003:Ploidies; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D015203:Reproducibility of Results; D013548:Sweden; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D015415:Biomarkers; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D004247:DNA