title: Immunostaining for p16INK4a used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia.
abstract: The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16INK4a, a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study, we assessed whether p16INK4a immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p16INK4a-stained slide in conjunction to the H&E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch and cone biopsies (P < 0.001). For punch biopsies (n = 247), kappa value increased from 0.49 (moderate agreement) to 0.64 indicating substantial agreement, and interobserver agreement for cone biopsies (n = 249) improved from 0.63 (conventional H&E slide reading) to 0.70 when H&E-stained slides were read conjunctively with p16INK4a-stained slides. In comparison to a common consensus diagnosis established by 3 independent experts, 4 pathologists reached an improvement with the conjunctive p16INK4a test, 2 of them showing significantly better agreement (P < 0.001 and P = 0.002, respectively), p16INK4a immunohistochemistry as an adjunct to conventional H&E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia and may be a valuable aid for the interpretation of cervical histology.
authors.affiliation: Institute of Pathology, University of Leipzig, Germany.
authors.forename: Lars-Christian
authors.initials: LC
authors.lastname: Horn
authors.forename: Anja
authors.initials: A
authors.lastname: Reichert
authors.forename: Anne
authors.initials: A
authors.lastname: Oster
authors.forename: Sanne Frost
authors.initials: SF
authors.lastname: Arndal
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Trunk
authors.forename: Ruediger
authors.initials: R
authors.lastname: Ridder
authors.forename: Ole Feldballe
authors.initials: OF
authors.lastname: Rassmussen
authors.forename: Kaj
authors.initials: K
authors.lastname: Bjelkenkrantz
authors.forename: Pernille
authors.initials: P
authors.lastname: Christiansen
authors.forename: Matthias
authors.initials: M
authors.lastname: Eck
authors.forename: Thomas
authors.initials: T
authors.lastname: Lorey
authors.forename: Vibeke Ravn
authors.initials: VR
authors.lastname: Skovlund
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruediger
authors.forename: Volker
authors.initials: V
authors.lastname: Schneider
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmidt
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D004396:Coloring Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004801:Eosine Yellowish-(YS); D005260:Female; D006416:Hematoxylin; D006801:Humans; D007150:Immunohistochemistry; D015588:Observer Variation; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004396:Coloring Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin