title: Eukaryotic initiation factor 5A-1 (eIF5A-1) as a diagnostic marker for aberrant proliferation in intraepithelial neoplasia of the vulva.
abstract: OBJECTIVE
  The mature eukaryotic translation initiation factor 5A contains the unusual amino acid hypusine, formed post-translationally from a specific lysine residue and essential for proliferation of eukaryotic cells. We hypothesized that the major eIF5A isoform, eIF5A-1, is an in situ biomarker for proliferation. NIH-353, a polyclonal immunoreagent specific for hypusine-containing eIF5A-1, was used to test this proposal in biopsies of vulvar high-grade intraepithelial neoplasia (VIN), characterized by the presence of proliferating cells throughout the thickness of the epithelium. Methods. Formalin-fixed and paraffin-embedded archival samples with an independently established diagnosis of VIN 3 were stained immunohistochemically after antigen retrieval, employing NIH-353 and, for comparison, the standard Ki-67 antibody.
  
  
  RESULTS
  NIH-353 labeled neoplastic keratinocytes throughout the thickness of the epithelium in all VIN 3 samples. Malignant cells in a case of focally invasive squamous cell carcinoma also stained strongly for mature, hypusine-containing eIF5A-1. Epithelium adjacent to these lesions, though still of apparently normal morphology, was immunoreactive throughout its full thickness. At inflammatory foci of lesional sites, solitary reactive lymphocytes were positive, as were individual proliferating cells within dermal appendages. The submucosal stroma lacked reactive cells.
  
  
  CONCLUSIONS
  NIH-353 identifies mature eIF5A-1 as an in situ biomarker for proliferation. Like Ki-67, this immunoreagent promises broad applicability in histopathological diagnosis and may be helpful in outcome prediction. In contrast to Ki-67, NIH-353 visualizes a molecular target for antineoplastic therapy, and thus may guide the development and clinical testing of drugs that, like the fungicide ciclopirox, inhibit hypusine formation and cell proliferation.
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, UMDNJ-New Jersey Medical School, Newark, NJ 07103-2714, USA.
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: Cracchiolo
authors.forename: Debra S
authors.initials: DS
authors.lastname: Heller
authors.forename: Paul M J
authors.initials: PM
authors.lastname: Clement
authors.forename: Edith C
authors.initials: EC
authors.lastname: Wolff
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Hartmut M
authors.initials: HM
authors.lastname: Hanauske-Abel
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D005260:Female; D006801:Humans; D010448:Peptide Initiation Factors / Q000032:analysis* / Q000276:immunology; D016601:RNA-Binding Proteins / Q000032:analysis* / Q000276:immunology; D014846:Vulvar Neoplasms / Q000175:diagnosis* / Q000473:pathology; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A