Polyoma virus-associated carcinomas of the urologic tract

a clinicopathologic and molecular study

Deepika Sirohi, Charlie Vaske, Zack Sanborn, Steven C. Smith, Michelle D. Don, Kathryn G. Lindsey, Scot Federman, Mahesha Vankalakunti, Jamie Koo, Shikha Bose, Mariza de Peralta-Venturina, Jessica van Ziffle, James P. Grenert, Steve Miller, Charles Chiu, Mahul Amin, Jeffry P. Simko, Bradley A. Stohr, Daniel J. Luthringer

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In recent years, there has been increased interest in carcinomas of the urologic tract, that demonstrate association with the polyoma virus BK arising in immunosuppressed individuals, though the nature of this association is uncertain. To begin to understand this phenomenon, we reviewed the clinical, morphological, and immunohistochemical features of 11 carcinomas of the urologic tract, mainly urothelial (N = 9) and collecting duct carcinomas (N = 2), occurring during immunosuppression, and expressing polyoma virus T-antigen by immunohistochemistry. These were compared to a control group of carcinomas (N = 8), also arising during immunosuppression, but without T-antigen expression. A subset of both groups were also studied by hybrid capture-based DNA sequencing, probing not only for 479 cancer-related human genes, but also for polyoma and other viral sequences. Polyoma T-antigen-expressing tumors arose in 7 males and 4 females, at a median age of 66, and were aggressive, high-grade tumors with more than 1 variant morphologic pattern identified in 81% of cases, and a majority (73%) presenting at high stage category (>pT3). Diffuse polyoma T-antigen staining was seen in 91% of cases, with co-localization of aberrant p53 staining in 89%. Sequencing detected a lower number of deleterious mutations among T-antigen-expressing cases (average 1.62; 1/8 with TP53 mutation) compared to control cases (average 3.5, 2/4 with TP53 mutation). Only BK virus was detected with clonal integration and breakpoints randomly distributed across the human and viral genomes in 5/5 of the polyoma T-antigen-expressing carcinomas, and in none of the controls (0/4). In summary, these findings identify aggressive clinicopathologic features of polyoma T-antigen-expressing carcinomas, document BK as the strain involved, and associate BK viral integration with T-antigen expression and p53 aberrancy. While the apparent randomness of viral insertion sites is functionally unclear, the differing rates of mutations between T-antigen-expressing and control cases is intriguing.

Original languageEnglish (US)
Pages (from-to)1429-1441
Number of pages13
JournalModern Pathology
Volume31
Issue number9
DOIs
StatePublished - Sep 1 2018

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Polyomavirus
Viral Tumor Antigens
Carcinoma
Immunosuppression
Mutation
BK Virus
Staining and Labeling
Virus Integration
Neoplasms
Viral Genome
Human Genome
Mutation Rate
DNA Sequence Analysis
Renal Cell Carcinoma
Immunohistochemistry
Control Groups

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Sirohi, D., Vaske, C., Sanborn, Z., Smith, S. C., Don, M. D., Lindsey, K. G., ... Luthringer, D. J. (2018). Polyoma virus-associated carcinomas of the urologic tract: a clinicopathologic and molecular study. Modern Pathology, 31(9), 1429-1441. https://doi.org/10.1038/s41379-018-0065-z

Polyoma virus-associated carcinomas of the urologic tract : a clinicopathologic and molecular study. / Sirohi, Deepika; Vaske, Charlie; Sanborn, Zack; Smith, Steven C.; Don, Michelle D.; Lindsey, Kathryn G.; Federman, Scot; Vankalakunti, Mahesha; Koo, Jamie; Bose, Shikha; de Peralta-Venturina, Mariza; van Ziffle, Jessica; Grenert, James P.; Miller, Steve; Chiu, Charles; Amin, Mahul; Simko, Jeffry P.; Stohr, Bradley A.; Luthringer, Daniel J.

In: Modern Pathology, Vol. 31, No. 9, 01.09.2018, p. 1429-1441.

Research output: Contribution to journalArticle

Sirohi, D, Vaske, C, Sanborn, Z, Smith, SC, Don, MD, Lindsey, KG, Federman, S, Vankalakunti, M, Koo, J, Bose, S, de Peralta-Venturina, M, van Ziffle, J, Grenert, JP, Miller, S, Chiu, C, Amin, M, Simko, JP, Stohr, BA & Luthringer, DJ 2018, 'Polyoma virus-associated carcinomas of the urologic tract: a clinicopathologic and molecular study', Modern Pathology, vol. 31, no. 9, pp. 1429-1441. https://doi.org/10.1038/s41379-018-0065-z
Sirohi, Deepika ; Vaske, Charlie ; Sanborn, Zack ; Smith, Steven C. ; Don, Michelle D. ; Lindsey, Kathryn G. ; Federman, Scot ; Vankalakunti, Mahesha ; Koo, Jamie ; Bose, Shikha ; de Peralta-Venturina, Mariza ; van Ziffle, Jessica ; Grenert, James P. ; Miller, Steve ; Chiu, Charles ; Amin, Mahul ; Simko, Jeffry P. ; Stohr, Bradley A. ; Luthringer, Daniel J. / Polyoma virus-associated carcinomas of the urologic tract : a clinicopathologic and molecular study. In: Modern Pathology. 2018 ; Vol. 31, No. 9. pp. 1429-1441.
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AU - Don, Michelle D.

AU - Lindsey, Kathryn G.

AU - Federman, Scot

AU - Vankalakunti, Mahesha

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AU - van Ziffle, Jessica

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