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Original research
Three-antibody classifier for muscle invasive urothelial carcinoma and its correlation with p53 expression
  1. Ekaterina Olkhov-Mitsel1,
  2. Anjelica Hodgson2,
  3. Stanley K Liu3,
  4. Danny Vesprini3,
  5. Bin Xu2,
  6. Michelle R Downes1,4
  1. 1 Division of Anatomic Pathology, Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  2. 2 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
  3. 3 Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  4. 4 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Michelle R Downes, Division of Anatomic Pathology, Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; michelle.downes{at}sunnybrook.ca

Abstract

Aims To assess the utility of a three-antibody immunohistochemistry panel to classify muscle invasive bladder cancers (MIBCs) in correlation with morphological features and p53 status.

Methods A retrospective review of 243 chemotherapy naïve MIBC cystectomy specimens was performed to assess morphological features. A tissue microarray was sequentially stained with CK5/6, GATA-3 and p16. Subgroups were assigned as basal-like (CK5/6+, GATA3−) and luminal (CK5/6−, GATA3+), with the latter subdivided into genomically unstable (GU, p16+) and urothelial like (Uro, p16−) subgroups. p53 staining was assessed as abnormal/wild type. Cases from the The Cancer Genome Atlas (TCGA) portal were assessed as external validation.

Results We identified 78.8% luminal, 21.2% basal cases within our cohort and 63.4% luminal, 36.6% basal in the TCGA dataset. Divergent differentiation (p<0.001) was significantly associated with basal-subtype cases in both cohorts. Within the luminal subgroup (n=186), 81 cases were classified as GU and 105 as Uro. Abnormal p53 staining was noted in 48.0% of basal, 80.2% GU and 38.1% Uro cases. Further, basal-subtype tumours significantly correlated with disease-specific death compared with Uro cases in multivariate survival analysis.

Conclusions This retrospective study demonstrates the potential utility of a three-antibody immunohistochemistry panel to differentiate luminal and basal MIBC.

  • morphology
  • immunohistochemistry
  • pathology
  • molecular
  • urinary bladder

Data availability statement

Data are available on reasonable request.

http://dx.doi.org/10.1136/jclinpath-2021-207573

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    Data availability statement

    Data are available on reasonable request.

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    Footnotes

    • Handling editor Runjan Chetty.

    • Contributors MRD designed the study. AH, BX and MRD gathered the immunohistochemistry data. EO-M, AH, SKL, DV, BX and MRD reviewed and interpreted the data. EO-M performed the statistical analysis. EO-M, AH, SKL, DV, BX and MRD contributed to drafting and review of the manuscript, and to approval of the final version.

    • Funding Sunnybrook Health Sciences Centre departmental Educational Grant.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.