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Uroplakin II as a single marker for luminal versus basal molecular subtypes in muscle invasive urothelial carcinoma

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Abstract

Bladder cancer is a heterogeneous disease classified into two broad molecular subtype categories, basal and luminal, with critical treatment and prognostic implications. Recent studies have shown the utility of immunohistochemistry in predicting bladder cancer molecular subtypes, with a two-marker approach using GATA3 and CK5/6 showing over 80% reliability. In the current study, we calculated the accuracy of uroplakin II (UPII), a marker of urothelial differentiation, with different scores (0: <1%, 1+: 1–10%, 2+: 10–50%, 3+: >50%) to predict RNA-based luminal versus basal subtypes in a cohort of muscle-invasive bladder cancer-received neoadjuvant chemotherapy followed by radical cystectomy. The 1% cutoff of the UPII stain predicts the luminal subtype with the sensitivity and specificity of 95% and 56%, respectively. With a UPII cutoff of 10%, the sensitivity and specificity were 93% and 81%, respectively, and with a UPII cutoff of 50%, the sensitivity and specificity were 91% and 96%, respectively. The prediction performance of UPII was better than either GATA3 or CK5/6. There was no significant difference in prognoses between UPII 0–2+ and UPII 3+ patients in this cohort. The current study shows that evaluating the staining proportion score of UPII can accurately predict basal and luminal subtypes of muscle-invasive bladder cancer.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

G.W. received New Faculty Research Award from University of British Columbia

Author information

Authors and Affiliations

  1. Department of Pathology, University of British Columbia, Vancouver, BC, Canada

    Collin Pryma, Carlos Villamil & Gang Wang

  2. Department of Pathology, British Columbia Cancer Vancouver Centre, 600 West 10th Avenue, Vancouver, BC, V5Z 1H5, Canada

    Carlos Villamil & Gang Wang

  3. Decipher Urological Cancers, Veracyte, Inc., Vancouver, BC, Canada

    Ewan A. Gibb

  4. Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

    Htoo Zarni Oo, Alberto Contreras-Sanz & Peter C. Black

  5. Department of Urology, University Hospital Bern, Bern, Switzerland

    Roland Seiler

  6. Department of Urology, University Hospital of Southampton, Hampshire, UK

    James Douglas

Authors
  1. Collin Pryma
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  2. Carlos Villamil
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  3. Ewan A. Gibb
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  4. Htoo Zarni Oo
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  5. Roland Seiler
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  7. James Douglas
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  8. Peter C. Black
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  9. Gang Wang
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Contributions

C.P. and G.W. performed study concept and design; C.P., C.V., E.G., P.B., and G.W. performed the development of methodology and writing, review, and revision of the paper; C.P., C.V., E.G., H.Z.O., R.S., A.C., J.D., P.B., and G.W. provided acquisition, analysis and interpretation of data, and statistical analysis. All authors read and approved the final paper.

Corresponding author

Correspondence to Gang Wang.

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Supplementary information

Suppl Fig 1

Kaplan-Meier survival analyses of the outcome ofthe patients with GATA3 0-2+ compared with those with GATA3 3+. A. There was nosignificant difference in cancer-specific survival (p > 0.05). B. There was nosignificant difference in overall survival (p > 0.05). (PNG 572 kb)

High resolution image (TIF 857 kb)

Suppl Fig 2

Kaplan-Meier survival analyses of the outcome ofthe patients with CK5/6 0-1+ compared with those with GATA3 2+-3+. A. There wasno significant difference in cancer-specific survival (p > 0.05). B. There wasno significant difference in overall survival (p > 0.05). (PNG 495 kb)

High resolution image (TIF 756 kb)

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Pryma, C., Villamil, C., Gibb, E.A. et al. Uroplakin II as a single marker for luminal versus basal molecular subtypes in muscle invasive urothelial carcinoma. Virchows Arch 481, 397–403 (2022). https://doi.org/10.1007/s00428-022-03346-z

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  • DOI: https://doi.org/10.1007/s00428-022-03346-z

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