title: HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis.
abstract: Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16(INK4A) and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16(INK4A) and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16(INK4A) and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16(INK4A) expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.
authors.affiliation: Centre for Molecular Oncology and Imaging, Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Stankiewicz
authors.forename: Sakunthala C
authors.initials: SC
authors.lastname: Kudahetti
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: 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: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018289:Carcinoma, Verrucous / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology; D010412:Penile Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D016133:Polymerase Chain Reaction; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53