title: The expression patterns of p53 and p16 and an analysis of a possible role of HPV in primary adenocarcinoma of the urinary bladder.
abstract: BACKGROUND
  Primary adenocarcinoma of the urinary bladder is rare. The molecular and cellular events leading to its pathogenesis are not well delineated. The goal of this study was to investigate p53 and p16 expression, as well as HPV status, in a relatively large series of primary bladder adenocarcinomas.
  
  
  METHODS
  Thirty six cases of urinary bladder adenocarcinoma were chosen from participating institutions. The diagnosis and available clinical history were reviewed in each case. Immunostains for p53, p16 and HPV and high-risk and low-risk HPV-ISH were performed on all tumors.
  
  
  RESULTS
  Patients had an average age of 61 years with a male predominance (1.5 ∶ 1 male ∶ female ratio). The average tumor size in cystectomy specimens was 4.3 cm. Of the cases managed by transurethral resection, 40% were pT2 at the time of diagnosis. In cystectomy specimens, 77% were either pT3 or pT4. Strong nuclear p16 expression was seen in 67% of all cases and p53 expression was present in 58% of the cases. Expression of both markers was seen in 33% of cases. Expression of p16 or p53 alone was present in 12 (33%) and 9 (25%) cases, respectively. Neither marker was expressed in only 3 (8%) of the tumors. No significant correlation between clinical variables and any of the markers we studied was identified. No HPV infection was detected in any case.
  
  
  CONCLUSIONS
  Expression of p53 and/or p16 is very common in urinary bladder adenocarcinoma. These findings implicate a high likelihood that alterations in these cell cycle proteins contribute to the pathogenesis of these tumors. Despite frequent immunohistochemical labeling for p16, no evidence of HPV infection was found.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Riley E
authors.initials: RE
authors.lastname: Alexander
authors.affiliation: Department of Pathology, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Williamson
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Justin
authors.initials: J
authors.lastname: Richey
authors.affiliation: Department of Pathology, Cordoba University, Cordoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.affiliation: Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Davidson
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Idrees
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Jones
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Rao
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Pedrosa
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Hristos Z
authors.initials: HZ
authors.lastname: Kaimakliotis
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: M Francesca
authors.initials: MF
authors.lastname: Monn
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Koch
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Urology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000382:microbiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53
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