title: Subcellular mislocalization of the transcription factor NF-E2 in erythroid cells discriminates prefibrotic primary myelofibrosis from essential thrombocythemia.
abstract: The World Health Organization (WHO) classification of myeloproliferative neoplasms (MPNs) comprises several entities including essential thrombocythemia (ET); primary myelofibrosis (PMF); and MPN, unclassifiable (MPN,U). Differential diagnosis between ET and early, prefibrotic PMF can be challenging but is critical because clinical course and outcome vary considerably between these entities. We have previously shown that the transcription factor nuclear factor erythroid 2 (NF-E2) is aberrantly expressed in MPN patients. Here we demonstrate that NF-E2 is mislocalized in PMF cells and that aberrant NF-E2 localization discriminates statistically highly significantly between ET and PMF. A threshold of 20% nuclear NF-E2 staining was cross-validated by ".682+ bootstrapping." Moreover, this cutoff correctly classifies diagnostic bone marrow biopsies of MPN,U patients specified upon follow-up as ET or PMF with 92% accuracy. Because interobserver concordance between independent pathologists was high (Spearman's rank correlation coefficient, 0.727), we propose that quantitative NF-E2 immunohistochemistry represents a diagnostic tool that can reliably support a differential diagnosis between ET and PMF.
authors.affiliation: Institute of Pathology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Aumann
authors.forename: Anna-Verena
authors.initials: AV
authors.lastname: Frey
authors.forename: Annette M
authors.initials: AM
authors.lastname: May
authors.forename: Dieter
authors.initials: D
authors.lastname: Hauschke
authors.forename: Clemens
authors.initials: C
authors.lastname: Kreutz
authors.forename: Jan P
authors.initials: JP
authors.lastname: Marx
authors.forename: Jens
authors.initials: J
authors.lastname: Timmer
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.forename: Heike L
authors.initials: HL
authors.lastname: Pahl
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001706:Biopsy; D015331:Cohort Studies; D003937:Diagnosis, Differential; D041905:Erythroid Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000378:metabolism*; D015588:Observer Variation; D055728:Primary Myelofibrosis / Q000175:diagnosis* / Q000473:pathology*; D011379:Prognosis; D011990:Receptors, Transferrin / Q000378:metabolism; D013920:Thrombocythemia, Essential / Q000175:diagnosis* / Q000473:pathology*; D014015:Tissue Banks
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; D011990:Receptors, Transferrin