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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. 1Division of Anatomic Pathology, Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  2. 2Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
  3. 3Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  4. 4Department 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.

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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.

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