title: Stathmin is a highly sensitive and specific biomarker for vulvar high-grade squamous intraepithelial lesions.
abstract: OBJECTIVE
  Differentiating between human papilloma virus-dependent vulvar low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) remains difficult in selected cases. Stathmin, a protein involved in cell cycle progression, might be a useful additional marker for this differentiation. The aim of this study was to investigate the additional diagnostic value of stathmin expression in vulvar intraepithelial neoplastic (VIN) lesions.
  
  
  METHODS
  Immunohistochemical analysis was used to evaluate stathmin, P16 and Ki67 expression in 91 samples, including LSILs (n=16), HSILs (n=50), differentiated VIN (dVIN; n=10), lichen sclerosis (LS; n=10) and normal vulvar tissue (n=5).
  
  
  RESULTS
  Stathmin was expressed in more than one-third of the epithelium in all HSILs and in 20% of LSILs. P16 and Ki67 were expressed in more than one-third of the epithelium in 94% of HSILs and in 13% and 40% of LSILs, respectively. Stathmin was expressed in more than one-third of the epithelium in 10% of the dVIN and in none of the LS or normal lesions. P16 and Ki67 expression was not present in more than one-third of the epithelium in any of these lesions. The sensitivity of stathmin for differentiating between LSILs and HSILs was 100% compared with a sensitivity of 94% for both p16 and Ki67. The specificity of stathmin, p16 and Ki67 was 80%, 87% and 60%, respectively.
  
  
  CONCLUSIONS
  Stathmin is a highly sensitive and specific biomarker for the diagnosis of vulvar HSIL. In addition to the more commonly used immunohistochemical markers p16 and Ki67, stathmin can be a useful diagnostic tool for identifying HSILs, especially in cases in which differentiating between LSIL and HSIL is difficult.
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.|Department of Gynaecology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Nooij
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Enno J
authors.initials: EJ
authors.lastname: Dreef
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.affiliation: Department of Gynaecology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mariëtte I E
authors.initials: MI
authors.lastname: van Poelgeest
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tjalling
authors.initials: T
authors.lastname: Bosse
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000145:classification* / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D060787:Neoplasm Grading; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000145:classification* / Q000378:metabolism; D012680:Sensitivity and Specificity; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000145:classification* / Q000378:metabolism; D050777:Stathmin / Q000378:metabolism*; D014844:Vulva / Q000473:pathology; D014846:Vulvar Neoplasms / Q000145:classification* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C493995:STMN1 protein, human; D050777:Stathmin
keywords: GYNAECOLOGICAL PATHOLOGY; HPV; IMMUNOHISTOCHEMISTRY