title: Etiological role of human papillomavirus infection for inverted papilloma of the bladder.
abstract: The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin-fixed and paraffin-embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV-DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri-Max HPV genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV-18 was detected in two cases, including one inverted papilloma with atypia, and HPV-16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High-risk HPV was present in all HPV-positive cases. Cellular proteins, p16-INK4a and mcm7, which are surrogate markers for HPV-E7 expression, were detected in all HPV-positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High-risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential.
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Shigehara
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sasagawa
authors.forename: John
authors.initials: J
authors.lastname: Doorbar
authors.forename: Shohei
authors.initials: S
authors.lastname: Kawaguchi
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Kobori
authors.forename: Takao
authors.initials: T
authors.lastname: Nakashima
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shimamura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Maeda
authors.forename: Tohru
authors.initials: T
authors.lastname: Miyagi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kadono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizokami
authors.forename: Eitetsu
authors.initials: E
authors.lastname: Koh
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
mesh_terms: D000328:Adult; D000368:Aged; D036022:Capsid Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004261:DNA Replication; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000302:isolation & purification*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D064168:Minichromosome Maintenance Complex Component 7; D009687:Nuclear Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D018308:Papilloma, Inverted / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications* / Q000175:diagnosis*; D016133:Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000821:virology*
chemical_list: D036022:Capsid Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C114580:HPV L1 protein, Human papillomavirus; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7