There is a clinical need to identify novel biomarkers to improve diagnostic accuracy for the detection of urothelial tumors. The current study aimed to evaluate keratin 17 (K17), an oncoprotein that drives cell cycle progression in cancers of multiple anatomic sites, as a diagnostic biomarker of urothelial neoplasia in bladder biopsies and in urine cytology specimens. We evaluated K17 expression by immunohistochemistry in formalin-fixed, paraffin embedded tissue specimens of non-papillary invasive urothelial carcinoma (UC) (classical histological cases), high grade papillary UC (PUC-LG), low grade papillary UC (PUC-HG), papillary urothelial neoplasia of low malignant potential (PUNLMP), and normal bladder mucosa. A threshold was established to dichotomize K17 status in tissue specimens as positive vs. negative, based on the proportion of cells that showed strong staining. In addition, K17 immunocytochemistry was performed on urine cytology slides, scoring positive test results based on the detection of K17 in any urothelial cells. Mann–Whitney and receiver operating characteristic analyses were used to compare K17 expression between histologic diagnostic categories. The median proportion of K17 positive tumor cells was 70% (range 20–90%) in PUNLMP, 30% (range 5–100%) in PUC-LG, 20% (range 1–100%), in PUC-HG, 35% (range 5–100%) in UC but staining was rarely detected (range 0–10%) in normal urothelial mucosa. Defining cases in which K17 was detected in ≥10% of cells were considered positive, the sensitivity of K17 in biopsies was 89% (95% CI: 80–96%) and the specificity was 88% (95% CI: 70–95%) to distinguish malignant lesions (PUC-LG, PUC-HG, and UC) from normal urothelial mucosa. Furthermore, K17 immunocytochemistry had a sensitivity of 100% and a specificity of 96% for urothelial carcinoma in 112 selected urine specimens. Thus, K17 is a sensitive and specific biomarker of urothelial neoplasia in tissue specimens and should be further explored as a novel biomarker for the cytologic diagnosis of urine specimens.

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The Stony Brook Medicine BioBank provided tissue blocks for immunohistochemical studies.


This work was supported by academic enrichment funds of the Department of Pathology at Stony Brook Medicine and KDx Diagnostic Inc.

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Author notes

  1. These author contributed equally: Luisa F. Escobar-Hoyos, Kenneth R. Shroyer


  1. Department of Pathology, Stony Brook Medicine, Stony Brook, NY, USA

    • Sruthi Babu
    • , Daniel C. Mockler
    • , Lucia Roa-Peña
    • , Agnieszka Szygalowicz
    • , Richard Moffitt
    • , Luisa F. Escobar-Hoyos
    •  & Kenneth R. Shroyer
  2. Program of Public Health and Department of Preventative Medicine, Stony Brook Medicine, Stony Brook, NY, USA

    • Sruthi Babu
  3. KDx Diagnostics Inc, Campbell, CA, USA

    • Nam W. Kim
    • , Sholeh Jahanfard
    •  & Shahram S. Gholami
  4. Department of Biomedical Informatics, Stony Brook Medicine, Stony Brook, NY, USA

    • Richard Moffitt
  5. Department of Urology, Stony Brook Medicine, Stony Brook, NY, USA

    • John P. Fitzgerald
  6. David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA

    • Luisa F. Escobar-Hoyos
  7. Department of Biology, Genetic Toxicology and Cytogenetics Research Group, School of Natural Sciences and Education, Universidad Del Cauca, Popayán, Colombia

    • Luisa F. Escobar-Hoyos


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Conflict of interest

N.W.K. and S.J. are employees of KDx Diagnostics Inc. and S.S.G. is a Chief Medical Officer of KDx. K.R.S., L.F.E.-H., N.W.K. are co-Inventors for Keratin 17 as a biomarker for bladder cancer (SBU Ref: R-8855-conversion deadline; US provisional Application No. 62/371,286; SSMP Docket: 33851P, International Publication number WO 2018/027091 A1). The remaining authors declare that they have no conflict of interest.

Corresponding authors

Correspondence to Luisa F. Escobar-Hoyos or Kenneth R. Shroyer.

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