title: Lack of P16ink4a over expression in penile squamous cell carcinoma is associated with recurrence after lymph node dissection.
abstract: OBJECTIVE
  There have been conflicting data in studies on the prognostic role of high risk human papillomavirus in penile squamous cell carcinoma. Using P16(ink4a) over expression as a surrogate marker for high risk human papillomavirus, we evaluated high risk human papillomavirus status with respect to various clinical features, including recurrence and overall survival, among others.
  
  
  METHODS
  P16(ink4a) over expression was evaluated by immunohistochemistry for 119 consecutive patients with penile squamous cell carcinoma. Several variables were recorded including age, stage, histological grade, lymph node status, lymphovascular invasion, metastasis and recurrence. Median followup was 30 months.
  
  
  RESULTS
  P16(ink4a) over expression was detected in 49.5% (59 of 119) of samples. There was no significant difference between P16(ink4a) negative and P16(ink4a) positive tumors in terms of stage (p = 0.518), histological grade (p = 0.225), lymphovascular invasion (p = 0.388), overall survival (p = 0.156) or lymph node metastasis (p = 0.748). P16(ink4a) negative tumors were more likely to recur overall (p = 0.04), especially if patients had positive lymph nodes at diagnosis (p = 0.002).
  
  
  CONCLUSIONS
  These data suggest that P16(ink4a)/high risk human papillomavirus status is associated with recurrence, especially in patients with positive lymph nodes at diagnosis. Thus, patients with P16(ink4a) negative penile cancer, particularly those with lymph node metastases, may warrant closer observation after surgery.
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Dominic H
authors.initials: DH
authors.lastname: Tang
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clark
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giannico
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Omar
authors.initials: O
authors.lastname: Hameed
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Sam S
authors.initials: SS
authors.lastname: Chang
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Lan L
authors.initials: LL
authors.lastname: Gellert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary / Q000601:surgery*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D010412:Penile Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D012189:Retrospective Studies
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: carcinoma; genes; p16; penis; recurrence; squamous cell