Prostate-Specific Antigen, High-Molecular-Weight Cytokeratin (Clone 34βE12), and/or p63

Abstract

An optimal immunohistochemical panel to distinguish poorly differentiated prostate (PCa) from urothelial (UCa) carcinoma was selected from a panel consisting of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), high-molecular-weight cytokeratin (HMWCK), clone 34betaE12, cytokeratin (CK) 7, CK20, p63, and alpha-methylacyl-coenzyme A racemase. The pilot group was composed of poorly differentiated UCa (n = 36) and PCa (n = 42). PSA and PAP stained 95% of PCa vs 0% and 11% of UCa cases, respectively. HMWCK and p63 stained 97% and 92% of UCa vs 2% and 0% of PCa cases respectively. CK7/CK20 coexpression was noted in 50% of UCa cases, whereas 86% of PCa cases were negative with both. A panel of PSA, HMWCK, and p63 was optimal for separating 95% PCa (PSA+/HMWCK and/or p63-) vs 97% UCa (PSA-/HMWCK and/or p63+). This panel was used on 26 diagnostically challenging cases and resolved 81% of cases as UCa vs PCa. The majority of PCa cases retain PSA. Negative PSA with positive HMWCK and/or p63 establishes a diagnosis of UCa.

Differential Immunohistochemical Profiles for Distinguishing Prostate Carcinoma and Urothelial Carcinoma

“…Many UCs retain a pattern of p63 expression, but p63 expression may be partially lost in high-grade UC [3,27]. Although p63 sensitivity for UC in our study (73.9%) was lower than that of previous studies (82.9%–91.7%) [3,6], its specificity was 100% for UC.…”

“…Monoclonal antibodies to PAP have been reported to have lower sensitivities than their polyclonal counterparts but be more specific [2]. PAP staining has been known to be consistently negative in UC [5,10,17], but a recent study reported immunopositivity in 11.1% of UC [6]. Unexpectedly, we also detected PAP staining with a scattered pattern in 26 of 138 cases of UC (18.8%).…”

“…It is reported to match the sensitivity of p63 and surpass that of uroplakin III and thrombomodulin [3,25]. Compared with previous studies showing sensitivities of 97.2%, 91.4%, and 65.2% for CK34βE12 in UC [3,6,10], our study found 75.4% sensitivity in UC. It is worth noting that CK34βE12 can label squamous epithelia, including areas of squamous differentiation in recurrent PAC after therapy.…”

“…PSA has been shown to be a highly specific marker, but some authors suggest that there is an inverse correlation between the Gleason score and PSA staining intensity [9]. Previous studies have reported that high-grade PAC that was completely negative for PSA stain ranged from 3% to 27% [3,5,6,9,10]. However, in our study, no PAC specimens were devoid of PSA expression, including high-grade PAC, with 100% sensitivity.…”

“…However, AMACR expression has repeatedly been demonstrated in HG-PIN and some benign mimickers of PAC. Moreover, Kunju et al [6] reported that AMACR is expressed in 36% of UC cases. In our study, AMACR was expressed in 66.7% of 111 cases of PAC and 8.7% of 138 cases of UC.…”