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Evaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas

Am J Clin Pathol. 2014 Aug;142(2):173-83.

Am J Clin Pathol. 2014 Aug;142(2):173-83.



New immunohistochemical (IHC) markers of urothelial carcinoma (UCa) and prostatic adenocarcinoma (PCa) have emerged in recent years, yet comparative studies to establish markers remain lacking. We aimed to identify an effective but parsimonious approach for poorly differentiated bladder neck lesions, to establish a best practice panel approach in a setting simulating prospective use.


We tested the performance of a panel of IHC markers on whole sections of a consecutive cohort of transurethral resection specimens of poorly differentiated, challenging bladder neck resections (n=36).


In the setting of poorly differentiated bladder neck carcinomas, biomarker sensitivities for UCa were as follows: GATA3, 100%; S100P, 88%; p63, 75%; and cytokeratin (CK) 5/6, 56%; specificities of each were 100%. CK7 and CK20 showed sensitivities of 75% and 63%, though these were only 85% and 80% specific. For PCa markers, NKX3.1, p501S, prostate-specific membrane antigen, and androgen receptor (AR) each showed 100% sensitivity, outperforming ERG (35%) and prostate-specific antigen (PSA; 25%). All the prostate histogenesis markers were 100% specific, except for AR, which was positive in 13% of the UCa cases.


Novel IHC markers show improved diagnostic performance that enables positive and negative support for identifying histogenesis with the use of as few as two markers for this critical therapeutic distinction. PSA underperforms newer markers.

Copyright© by the American Society for Clinical Pathology.


AR; Bladder neck; ERG; GATA3; Immunohistochemistry; NKX3.1; PSMA; Prostatic adenocarcinoma; S100P; Urothelial carcinoma; p501S

Comment from Maria Ribal: Poorly differentiated carcinoma arising on the bladder neck could generate controversies regarding the primary tumour site, since both bladder and prostate undifferentiated carcinomas can affect bladder neck during local growth. Authors provide results on IHC markers for addressing histogenesis in difficult cases. They do suggest that at least two lineage-specific markers each for urothelial carcinoma (GATA3, S100P) and prostate cancer (NKX3.1, p501S, PSMA) should be tested in those challenging cases.