p16 and HPV ISH Expression in Urothelial Carcinoma with Squamous Differentiation and Primary Squamous Cell Carcinoma of the Urinary Bladder: An Institutional Review
Keith A Stevens, Adeboye O Osunkoya. Emory University School of Medicine, Atlanta, GA
Background: Human papilloma virus (HPV) has a well established role in the oncogenesis of numerous premalignant and malignant squamous lesions, especially those of the gynecologic tract and oropharynx. p16 protein is usually overexpressed in cells infected with HPV, and is often used as a surrogate marker for HPV infection at these sites. The role of HPV infection in squamous lesions of the urinary bladder remains questionable, and reported rates of HPV infection at this site have varied widely. In this study, we sought to further characterize p16 expression patterns in malignant bladder tumors with squamous morphology, and to evaluate the possible role of HPV in the oncogenesis of these tumors.
Design: A search was made through our surgical pathology files, and expert consultation files of the senior author, for cases of urothelial carcinoma with squamous differentiation (UCASD) and primary squamous cell carcinoma (SCC) of the bladder from 2006-2012. Squamous cell carcinoma of the gynecologic tract was excluded in all female patients. Immunohistochemical analysis for p16 expression was performed on a representative section from each case. Cases were considered p16 positive if the tumor cells demonstrated diffuse 2+ or 3+ staining. In addition, each case was further evaluated for the presence of high risk HPV types 16 and 18 by in situ hybridization (ISH) probes.
Results: A total of 42 cases with available tissue blocks were identified. The majority of cases 34/42 (81%) were UCASD and 8/42 (19%) cases were primary SCC of the bladder. Thirty eight cases were resection specimens, and 4 were from biopsies. Mean patient age was 66 years (range: 37-93 years). There was a slight male predominance 23/42 (55%) and 19/42 (45%) patients were female. p16 was positive in 14/42 (33%) cases; 11/42 (26%)were UCASD and 3/42 (7%) were primary SCC of the bladder. Only 1/42 (2%) cases was positive for high risk HPV ISH, which was a case of p16 positive primary SCC of the bladder trigone in a 37 year old female.
Conclusions: Only a single case was positive for both p16 and high risk HPV ISH, suggesting that other cellular mechanisms must be responsible for p16 overexpression in the vast majority of cases in this setting. This study also highlights that p16 expression used in isolation, will be of little diagnostic utility in the distinction between squamous lesions of the bladder and squamous lesions arising from the cervix or vagina. We recommend the utilization of morphology, HPV ISH expression, and clinical/radiologic correlation in this setting.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 161, Monday Morning