title: HER-2/NEU overexpression in vulvar Paget disease: the Yale experience.
abstract: OBJECTIVE
  To determine the level of HER-2/neu overexpression in vulvar Paget disease (PD) in order to assess the possibility of using HER-2/neu as a target for the treatment of Paget disease.
  
  
  METHODS
  A medical record search identified 39 patients with a histologically confirmed diagnosis of vulvar PD between 1986 and 2009. A tissue microarray containing all 39 tumour samples was created, and corresponding sections were stained immunohistochemically with an anti-HER-2/neu-antibody (HercepTest). Staining results were reported on a scale from 0 to 3+. 2+ and 3+ were considered as HER-2/neu overexpression. The HER-2/neu expression was correlated with clinical, pathological and outcome data.
  
  
  RESULTS
  Negative staining for HER-2/neu was noticed in four patients (12%), 1+ in 10 patients (30%), 2+ in 11 patients (33%) and 3+ in eight patients (25%), resulting in 19 patients with HER-2/neu overexpression (2+ and 3+, 58%) and 14 patients without HER-2/neu overexpression (0 and 1+, 42%). The proportion of HER-2/neu overexpression was higher in the patients with invasive than with non-invasive PD (71%, n=5/7 invasive PD vs 54%, n=14/26 non-invasive PD). There was no significant correlation between HER-2/neu staining results and clinical, pathological or outcome data.
  
  
  CONCLUSIONS
  Surgical treatment of vulvar Paget disease is associated with a high recurrence rate and extensive reconstructive procedures. In this study, over 50% of the patients with vulvar Paget disease overexpress HER-2/neu. Anti-HER-2/neu-antibodies like trastuzumab may therefore be an interesting treatment option for HER-2/neu-positive vulvar Paget disease. Clinical trials are needed to evaluate the efficacy of trastuzumab in this disease.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. christine.richter@yale.edu
authors.forename: Christine E
authors.initials: CE
authors.lastname: Richter
authors.forename: Pei
authors.initials: P
authors.lastname: Hui
authors.forename: Natalia
authors.initials: N
authors.lastname: Buza
authors.forename: Dan-Arin
authors.initials: DA
authors.lastname: Silasi
authors.forename: Masoud
authors.initials: M
authors.lastname: Azodi
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
authors.forename: Peter E
authors.initials: PE
authors.lastname: Schwartz
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rutherford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010145:Paget Disease, Extramammary / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016896:Treatment Outcome; D014846:Vulvar Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human