title: The prognostic value of Ki-67 expression in penile squamous cell carcinoma.
abstract: OBJECTIVE
  To determine whether Ki-67 immunoexpression in penile squamous cell carcinoma (PSCC) has a prognostic value and correlates with lymph node metastasis, human papillomavirus (HPV) infection and patient survival.
  
  
  METHODS
  148 formalin-fixed paraffin-embedded PSCC samples were tissue-microarrayed, including 97 usual-type SCCs, 17 basaloid, 15 pure verrucous carcinomas, 2 warty and 17 mixed-type tumours. All samples were immunostained for Ki-67 protein. HPV DNA was detected with INNO-LiPA assay. Follow-up data were available for 134 patients.
  
  
  RESULTS
  Ki-67 was strongly expressed in 57/148 (38.5%) of PSCCs. Different cancer subtypes showed significant difference in Ki-67 expression (p<0.0001) with highest positivity in basaloid, 16/17 (94%), followed by usual type, 38/97 (39%) and lack of Ki-67 positive cases within verrucous tumours, 0/15. Ki-67 positively correlated with high-risk HPV (p<0.0001) and showed good specificity (84%) but low sensitivity (61%) for high-risk HPV detection. Ki-67 protein strongly positively correlated with tumour grade (p<0.0001) but not with stage (p=0.2193), or lymph node status (p=0.7366). Ki-67 showed no prognostic value for cancer-specific survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.54) or overall survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.45). High tumour stage, lymph node metastasis, high tumour grade and age at diagnosis were all independent prognostic factors for cancer-specific survival and overall survival.
  
  
  CONCLUSIONS
  Ki-67 is only a moderate surrogate marker for HPV infection in PSCC. It does not show prognostic value for cancer-specific survival and overall survival in PSCC.
authors.affiliation: Department of Molecular Oncology, Barts Cancer Institute, London, UK. e.stankiewicz@qmul.ac.uk
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Stankiewicz
authors.forename: Mansum
authors.initials: M
authors.lastname: Ng
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.forename: David
authors.initials: D
authors.lastname: Mesher
authors.forename: Nick
authors.initials: N
authors.lastname: Watkin
authors.forename: Wayne
authors.initials: W
authors.lastname: Lam
authors.forename: Cathy
authors.initials: C
authors.lastname: Corbishley
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Berney
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D060787:Neoplasm Grading; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D010412:Penile Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000821:virology; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D019394:Ki-67 Antigen