title: Polyomavirus large T antigen is prevalent in urothelial carcinoma post-kidney transplant.
abstract: Viral pathogens have been associated with both infectious disease and neoplasia in transplant recipients. Polyomavirus is emerging as a potential causative agent for genitourinary tract cancer in post-kidney transplant patients. Human papillomavirus (HPV) has a proven role in squamous cancers, but has not been studied in genitourinary malignancies in transplantation. Of 2345 kidney transplants performed at our center over the past 20 years, we identified 16 patients with 20 genitourinary cancers (0.7%), including 13 bladder/ureter carcinomas, 5 renal cell carcinomas (RCCs), and 2 prostate carcinomas. We performed immunohistochemical staining for polyomavirus large T antigen and p16, followed by in situ hybridization for HPV in p16+ cases. Four cases of high-grade invasive urothelial bladder carcinomas were positive for large T. Large T+ urothelial carcinomas developed at least 8 years posttransplant in young men, 3 with history of BK polyoma viremia, 2 of whom had native kidney failure due to reflux/obstruction. In situ hybridization for high-risk HPV was negative in all tested cases. Overall, 3 patients died of carcinoma. All 5 RCCs were negative for both large T and p16; 2 prostate cancers were p16 negative and p16+/HPV negative, respectively. Thus, our study shows a relatively high prevalence of large T antigen in urothelial carcinoma in kidney transplant patients (31%), but not in RCC. Although sample size is small, young patients with obstructive disease may be at particular risk for developing large T-positive urothelial carcinoma. Overall, our data further support the necessities of long-term cancer surveillance for renal transplant patients.
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR 97239. Electronic address: yali@ohsu.edu.
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.affiliation: University of Utah & ARUP Reference Lab., Salt Lake City, UT 84108; Hematopathology Section, ARUP Reference Lab., Salt Lake City, UT 84108. Electronic address: mohamed.salama@path.utah.edu.
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Salama
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR 97239. Electronic address: lanciaul@ohsu.edu.
authors.forename: Christian
authors.initials: C
authors.lastname: Lanciault
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR 97239. Electronic address: matsumlm@ah.org.
authors.forename: Linh
authors.initials: L
authors.lastname: Matsumura
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR 97239; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239. Electronic address: troxellm@ohsu.edu.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Troxell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000957:Antigens, Viral, Tumor / Q000032:analysis / Q000096:biosynthesis*; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000821:virology*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology; D015995:Prevalence; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000821:virology*
chemical_list: D000957:Antigens, Viral, Tumor
keywords: Human papillomavirus; Kidney transplant; Large T antigen; Polyomavirus; Urothelial carcinoma