p53 immunohistochemistry in high-grade urothelial carcinoma of the bladder is prognostically significant.
OBJECTIVE
TP53 mutations are characteristic of the high-grade pathway in the dual pathway of urothelial carcinogenesis. These mutations have been correlated with aberrant accumulation of p53 protein; however the definition and significance of this vary in the literature. The aim of this study was to assess p53 immunostaining in a cohort of high-grade urothelial carcinomas by using standard published cut-offs and a novel binarized method that included assessment of the null phenotype. Each scoring method was correlated with oncological outcome.


RESULTS
A triplicate core tissue microarray was constructed from 207 cases of high-grade urothelial carcinoma treated by cystectomy, and was stained with p53. The percentage nuclear staining was recorded for each core and averaged for every case (206 cases were evaluable). Cases were categorized as positive/negative according to published cut-offs (10%, 40%) or by binarizing them as abnormal (null phenotype or >50% positivity) and wild type (1-49% positivity). Correlation with disease-specific survival was not significant according to standard definitions of p53 positivity. When a 40% cut-off was used, a correlation with relapse-free survival was significant on univariate analysis (P = 0.038) but not on multivariate analysis (P = 0.079). Abnormal p53 expression showed a near-significant trend for association with disease-specific survival (P = 0.052) and was a significant predictor for relapse-free survival on both univariate analysis (P = 0.047) and multivariate analysis (P = 0.035).


CONCLUSIONS
Prior to this study, the p53 null phenotype was not well described in urothelial carcinoma of the bladder. Abnormal p53 immunoexpression (null staining pattern or staining in >50% of cells) is prognostic in terms of oncological outcome.
Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Anjelica
http://orcid.org/0000-0002-4069-2000
A
Hodgson
Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Bin
http://orcid.org/0000-0003-4638-9835
B
Xu
Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Michelle R
http://orcid.org/0000-0002-4528-3724
MR
Downes
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
bladder; p53; prognosis; urothelial carcinoma