title: Carcinogenesis of Vulvar Lesions: Morphology and Immunohistochemistry Evaluation.
abstract: OBJECTIVE
  The aim of the study was to assess the 2 pathways of vulvar carcinogenesis and correlate immunohistochemical expression of p53 with histopathological findings.
  
  
  METHODS
  This cross-sectional study included 76 cases. Patients were classified according to the 2004 International Society for the Study of Vulvovaginal Disease Terminology, followed by a review of clinical records and immunohistochemical staining for p53.
  
  
  RESULTS
  Fifteen cases were in the human papillomavirus (HPV)-associated pathway (12 cases of usual vulvar intraepithelial neoplasia [VIN] and 3 of warty squamous cell carcinoma [SCC]), and 13 cases were in the HPV-independent pathway (5 cases of differentiated VIN and 8 of keratinizing SCC). Significant differences in p53 expression were observed between the 2 pathways of carcinogenesis: in the lesions related to the HPV-independent pathway, the percentage of p53-positive cells was greater (>25%, p < .001), and the staining pattern was basal (extending into the middle layer) in differentiated VIN and diffuse or infiltrative in warty SCC (p < 0.001). In the lesions HPV-associated pathway, p53 staining was less extensive (≤10% of cells, p < 0.001) and followed basal pattern in usual VIN, whereas warty SCCs were negative for p53 (p < 0.001).
  
  
  CONCLUSIONS
  Unique patterns of histological appearance and p53 expression can separate vulvar lesions into 2 distinct pathways of carcinogenesis. We propose that p53 immunohistochemistry may be performed simultaneously with histopathological examination in all cases of VIN and vulvar SCC, because it would aid in definition of the pathway of carcinogenesis and thus enable better clinical follow-up of patients with these conditions.
authors.affiliation: 1Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, School of Medicine, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil; 2Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil; and Departments of 4Pathology and 5Obstetrics and Gynecology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Raquel Camara
authors.initials: RC
authors.lastname: Rivero
authors.forename: Deborah
authors.initials: D
authors.lastname: Garcia
authors.forename: Luciano Serpa
authors.initials: LS
authors.lastname: Hammes
authors.forename: Marcelle Reesink
authors.initials: MR
authors.lastname: Cerski
authors.forename: Valentino
authors.initials: V
authors.lastname: Magno
authors.forename: Lúcia Maria
authors.initials: LM
authors.lastname: Kliemann
authors.forename: Edison
authors.initials: E
authors.lastname: Capp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis; D002277:Carcinoma / Q000473:pathology* / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014846:Vulvar Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53