title: Biomarkers p16, Human Papillomavirus and p53 Predict Recurrence and Survival in Early Stage Squamous Cell Carcinoma of the Vulva.
abstract: OBJECTIVE
  Vulvar squamous cell carcinoma (VSCC) develops through 2 distinct molecular pathways, one involving high-risk human papillomavirus (HPV) infection and the other through early p53 suppressor gene mutation. We sought to evaluate the influence of p53 mutation, HPV status, and p16 expression on local recurrence and disease-specific mortality in early stage VSCC.
  
  
  METHODS
  We performed a retrospective chart review of all patients with stage I VSCC at the Maine Medical Center from 1998 to 2007 (n = 92). Tumor size, depth of invasion, lymphatic/vascular space invasion, and growth pattern were recorded. Paraffin-embedded tissue blocks were stained by immunohistochemistry for p16 and p53; high-risk HPV was detected by polymerase chain reaction assay. Margin distance was determined by a gynecologic pathologist. Survival analyses were conducted to examine predictors of VSCC recurrence and disease-specific mortality.
  
  
  RESULTS
  Age, depth of invasion, lymphatic/vascular space invasion, growth pattern, and margin status were not significant predictors of recurrence or disease-specific mortality. Tumor size of greater than 4.0 cm indicated a 4-fold increase in disease-specific mortality but did not significantly increase recurrence. p16-Positive patients were less likely to recur and had no VSCC-related deaths. Human papillomavirus-positive patients were less likely to recur and had no VSCC-related deaths. p53-positive patients were 3 times more likely to recur and nearly 7 times more likely to die from vulvar cancer.
  
  
  CONCLUSIONS
  Our findings suggest that HPV and the surrogate biomarker p16 indicate a less aggressive type of vulvar cancer. p53 positivity was associated with poor prognosis and significantly increased both recurrence and disease-specific mortality.
authors: 1Department of Obstetrics and Gynecology, Maine Medical Center, Portland; 2Division of Gynecologic Oncology, Maine Medical Partners, Scarborough; and 3Center for Outcomes Research and Evaluation and 4Department of Pathology, Maine Medical Center, Portland, ME.
authors: Casey M
authors: CM
authors: Hay
authors: Jason A
authors: JA
authors: Lachance
authors: F L
authors: FL
authors: Lucas
authors: Kahsi A
authors: KA
authors: Smith
authors: Michael A
authors: MA
authors: Jones
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008281:Maine; D008853:Microscopy; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014846:Vulvar Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53