title: The retinoblastoma protein/p16 INK4A pathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma.
abstract: OBJECTIVE
  The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood. Human papillomavirus (HPV) may be involved in carcinogenesis, but few studies have compared cell-cycle protein expression in HPV positive and negative cancers. The aim was to determine the extent of HPV infection in different histological subtypes of PSCC and its impact on the expression of key cell-cycle proteins: p53, p21, p16(INK4A) and retinoblastoma (RB) protein.
  
  
  RESULTS
  One hundred and forty-eight PSCC samples were examined immunohistochemically for RB, p16(INK4A) , p53 and p21 protein expression. One hundred and two cases were typed for HPV by PCR. HPV DNA was detected in 56% of tumours, with HPV16 present in 81%. Basaloid tumours were related strongly to HPV infection (10 of 13), while verrucous were not (three of 13). Fifty-nine per cent (38 of 64) of usual type SCCs had HPV infection. RB protein correlated negatively (P<0.0001) and p16(INK4A) (P<0.0001) and p21 (P=0.0002) correlated positively with HPV infection. p53 did not correlate with HPV infection.
  
  
  CONCLUSIONS
  HPV infection is present in more than half of penile cancers and it is responsible for RB pathway disruption. However, no link between HPV and p53 immunodetection was found. Only basaloid and half of usual-type PSSCs correlate with HPV infection, confirming possible separate aetiologies for those tumours.
authors.affiliation: Queen Mary University of London, Centre for Molecular Oncology and Imaging, Barts and The London School of Medicine and Dentistry, London, UK. e.stankiewicz@qmul.ac.uk
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Stankiewicz
authors.forename: David M
authors.initials: DM
authors.lastname: Prowse
authors.forename: Elena
authors.initials: E
authors.lastname: Ktori
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.forename: Laurence
authors.initials: L
authors.lastname: Ambroisine
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhang
authors.forename: Sakunthala
authors.initials: S
authors.lastname: Kudahetti
authors.forename: Nicholas
authors.initials: N
authors.lastname: Watkin
authors.forename: Catherine
authors.initials: C
authors.lastname: Corbishley
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Berney
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D006801:Humans; D008297:Male; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology; D010412:Penile Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53