The Expression Patterns of p53 and p16 and an Analysis of a Possible Role of HPV in Primary Adenocarcinoma of the Urinary Bladder

• Published in: PloS one Vol. 9; no. 4; p. e95724
• Main Authors: Alexander, Riley E., Williamson, Sean R., Richey, Justin, Lopez-Beltran, Antonio, Montironi, Rodolfo, Davidson, Darrell D., Idrees, Muhammad T., Jones, Carol L., Zhang, Shaobo, Wang, Lisha, Rao, Qiu, Pedrosa, Jose A., Kaimakliotis, Hristos Z., Monn, M. Francesca, Koch, Michael O., Cheng, Liang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Analysis; Biology and Life Sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Bladder; Cancer; Cell cycle; Cyclin-Dependent Kinase Inhibitor p16; Diagnosis; Distribution; Female; Health aspects; Histology; Human papillomavirus; Humans; Hybridization; Immunohistochemistry; In Situ Hybridization; Infections; Institutions; Laboratories; Male; Markers; Medical prognosis; Medicine; Medicine and Health Sciences; Middle Aged; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; p53 Protein; Papillomavirus infections; Papillomavirus Infections - microbiology; Pathogenesis; Pathology; Proteins; Research and Analysis Methods; Senescence; Studies; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumorigenesis; Tumors; Urinary bladder; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urology; Indiana; United States > US; Indianapolis Indiana
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095724

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. 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. 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. 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.