Acta Neuropathologica

, Volume 124, Issue 4, pp 517–529

Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA

  • Piero Parchi
  • Laura de Boni
  • Daniela Saverioni
  • Mark L. Cohen
  • Isidro Ferrer
  • Pierluigi Gambetti
  • Ellen Gelpi
  • Giorgio Giaccone
  • Jean-Jacques Hauw
  • Romana Höftberger
  • James W. Ironside
  • Casper Jansen
  • Gabor G. Kovacs
  • Annemieke Rozemuller
  • Danielle Seilhean
  • Fabrizio Tagliavini
  • Armin Giese
  • Hans A. Kretzschmar
Original Paper

DOI: 10.1007/s00401-012-1002-8

Cite this article as:
Parchi, P., de Boni, L., Saverioni, D. et al. Acta Neuropathol (2012) 124: 517. doi:10.1007/s00401-012-1002-8

Abstract

The current classification of human sporadic prion diseases recognizes six major phenotypic subtypes with distinctive clinicopathological features, which largely correlate at the molecular level with the genotype at the polymorphic codon 129 (methionine, M, or valine, V) in the prion protein gene and with the size of the protease-resistant core of the abnormal prion protein, PrPSc (i.e. type 1 migrating at 21 kDa and type 2 at 19 kDa). We previously demonstrated that PrPSc typing by Western blotting is a reliable means of strain typing and disease classification. Limitations of this approach, however, particularly in the interlaboratory setting, are the association of PrPSc types 1 or 2 with more than one clinicopathological phenotype, which precludes definitive case classification if not supported by further analysis, and the difficulty of fully recognizing cases with mixed phenotypic features. In this study, we tested the inter-rater reliability of disease classification based only on histopathological criteria. Slides from 21 cases covering the whole phenotypic spectrum of human sporadic prion diseases, and also including two cases of variant Creutzfeldt–Jakob disease (CJD), were distributed blindly to 13 assessors for classification according to given instructions. The results showed good-to-excellent agreement between assessors in the classification of cases. In particular, there was full agreement (100 %) for the two most common sporadic CJD subtypes and variant CJD, and very high concordance in general for all pure phenotypes and the most common subtype with mixed phenotypic features. The present data fully support the basis for the current classification of sporadic human prion diseases and indicate that, besides molecular PrPSc typing, histopathological analysis permits reliable disease classification with high interlaboratory accuracy.

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Piero Parchi
    • 1
  • Laura de Boni
    • 2
  • Daniela Saverioni
    • 1
  • Mark L. Cohen
    • 3
  • Isidro Ferrer
    • 4
  • Pierluigi Gambetti
    • 3
  • Ellen Gelpi
    • 5
  • Giorgio Giaccone
    • 6
  • Jean-Jacques Hauw
    • 7
  • Romana Höftberger
    • 8
  • James W. Ironside
    • 9
  • Casper Jansen
    • 10
  • Gabor G. Kovacs
    • 8
  • Annemieke Rozemuller
    • 10
  • Danielle Seilhean
    • 7
  • Fabrizio Tagliavini
    • 6
  • Armin Giese
    • 2
  • Hans A. Kretzschmar
    • 2
  1. 1.IRCCS Istituto delle Scienze Neurologiche and Dipartimento di Scienze NeurologicheUniversità di BolognaBolognaItaly
  2. 2.Institut für NeuropathologieLudwig-Maximilians-UniversitätMunichGermany
  3. 3.National Prion Pathology Surveillance CentreCWRUClevelandUSA
  4. 4.Institut de Neuropatologia, Hospital Universitari de BellvitageUniversitat de BarcelonaBarcelonaSpain
  5. 5.Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPSBarcelonaSpain
  6. 6.Laboratorio di NeuropatologiaFondazione IRCCS Istituto Nazionale Neurologico Carlo BestaMilanItaly
  7. 7.APHP, Laboratoire de Neuropathologie Raymond EscourolleGH Pitiè-Salpêtrière Université Pierre et Marie Curie (UPMC-Paris 6), Sorbonne-UniversitésParisFrance
  8. 8.Institute of Neurology, AKH 4JMedical University of ViennaViennaAustria
  9. 9.National CJD Research and Surveillance UnitWestern General HospitalEdinburghUK
  10. 10.Dutch Surveillance Centre for Prion DiseasesUniversity Medical Centre UtrechtUtrechtThe Netherlands

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