Virchows Archiv

, Volume 475, Issue 6, pp 727–734 | Cite as

Molecular profiling of clear cell adenocarcinoma of the urinary tract

  • Chieh-Yu LinEmail author
  • Atif Saleem
  • Henning Stehr
  • James L. Zehnder
  • Benjamin A. Pinsky
  • Christian A. Kunder
Original Article


Clear cell adenocarcinoma (CCA) of the urinary tract is a rare type of malignancy whose molecular profiles remain undefined. Here we reported an integrated clinicopathologic and molecular profiling analysis of four cases of clear cell adenocarcinoma arising in the urethra or the bladder. Utilizing a clinically validated 130-gene exon-sequencing assay, we identified recurrent pathogenic PIK3CA (p. E545K) and KRAS (p.G12D) variants in three of four (75%) of the cases. In addition, an APC variant (P.S2310X), a TP53 variant (p.R273C), and a MYC amplification event were identified. The only CCA case without either PIK3CA or KRAS variants has a distinct pathogenesis through BK virus, demonstrated by positive BK virus PCR and SV40 immunohistochemistry. The novel finding of recurrent variants in the PI3K/AKT/mTOR pathway provides not only insights into oncogenesis but also potential clinical therapeutic targets for patients with clear cell adenocarcinoma of the urinary tract.


Clear cell adenocarcinoma Urinary tract Molecular profiling PIK3CA KRAS 



We thank Norman Cyr (graphic artist for the department of Pathology, Stanford) for the figure preparation and Nathaniel Taylor, MLS (ASCP)CMMB for technical support of the BK virus polymerase chain reaction (PCR) test.


C.-Y. Lin, the first author and corresponding author, designed the study, collected and analyzed the molecular profiling data, and prepared the manuscript and figures. A. Saleem collected the clinicopathologic data and prepared the manuscript and figures. H. Stehr and J. Zehnder contributed to the molecular data analysis and provided inputs for manuscript preparation. B. Pinsky assisted with BK virus analysis and provided inputs for manuscript preparation. C. Kunder reviewed the histologic sections as well as the molecular data, and provided inputs for manuscript preparation.

Compliance with ethical standards

Conflict of interest

Author C. A. Kunder’s spouse is an employee of Genentech. Other authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pathology and ImmunologyWashington University School of MedicineSt. LouisUSA
  2. 2.Department of PathologyStanford University School of MedicineStanfordUSA
  3. 3.Department of Medicine, Division of Infectious Diseases and Geographic MedicineStanford University School of MedicineStanfordUSA

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