Immunohistochemical Expression of Prostatic Antigens in Adenocarcinoma and Villous Adenoma of the Urinary Bladder

Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 10/2008; 32(9):1322-6. DOI: 10.1097/PAS.0b013e3181656ca0
Source: PubMed


Adenocarcinomas of the bladder are rare, with the diagnosis dependent on exclusion of secondary involvement by direct extension or metastatic spread from other sites. The recent description of an unusual form of urothelial-type mucinous prostatic adenocarcinoma raises a novel differential diagnosis between adenocarcinomas of the prostate and bladder, and investigation into the utility of classic prostatic immunohistochemical antigens in bladder adenocarcinoma is warranted. We identified 37 primary infiltrating adenocarcinomas of the bladder, which included signet ring cell carcinomas (n=11), urachal adenocarcinomas (n=5), and enteric adenocarcinoma (n=21). Also included for comparison were 3 cases, each of bladder villous adenomas and bladder adenocarcinoma in situ. Tissue microarrays were constructed from each case, with each specimen represented by multiple 1.0-mm cores to assess for tumor protein heterogeneity. Immunohistochemistry for prostate-specific antigen (PSA), prostate specific acid phosphatase (PSAP), P501S (prostein), and prostate specific membrane antigen (PSMA) was performed, and moderate to strong immunoreactivity was considered a positive result. Of the 37 adenocarcinomas, all were negative for PSA and PSAP (0/37; 0%). In contrast, a minority of bladder adenocarcinomas was labeled with the prostate antigens P501S and PSMA. P501S showed moderate diffuse cytoplasmic staining in 4/37 cases (11%), including 3 enteric-type adenocarcinomas and 1 mucinous adenocarcinoma. Additionally, 1 case of adenocarcinoma in situ demonstrated diffuse cytoplasmic staining for P501S. The granular perinuclear staining pattern of P501S typically seen in prostatic adenocarcinoma was absent in all cases of bladder adenocarcinoma. PSMA showed diffuse cytoplasmic staining in 4/37 (11%) infiltrating adenocarcinomas (including 1 signet ring carcinoma and 3 enteric-type adenocarcinomas), and in 1 case of adenocarcinoma in situ. Membranous PSMA staining was evident in an additional 3 tumors, 1 urachal mucinous adenocarcinoma, 1 nonurachal mucinous and signet ring cell adenocarcinoma, and 1 nonurachal villous adenoma. In conclusion, although all cases of bladder adenocarcinoma examined were negative for PSA and PSAP, the surprising finding that a subset of invasive and in situ adenocarcinomas of the bladder demonstrated immunoreactivity for P501S and PSMA should warrant caution when using these markers in differentiating prostatic from bladder adenocarcinomas. The lack of granular perinuclear staining for P501S and the absence of membranous PSMA staining both favor a bladder adenocarcinoma, although rare cases of villous adenoma and adenocarcinoma did show PSMA membranous staining indistinguishable from that seen in prostate cancer. Although the novel antigens P501S and PSMA are fairly specific and more sensitive in the differential diagnosis of prostate and urothelial carcinoma, care must be taken when adenocarcinomas of the bladder are considered within this differential diagnosis.

18 Reads
  • Source
    • "The granular perinuclear cytoplasmic expression of prostein is an important feature in establishing the prostatic origin of tumors. A recent study by Lane et al [18] found moderate diffuse cytoplasmic P501S staining in 11% of urinary bladder adenocarcinomas. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Distinguishing urothelial carcinoma (UC) from prostate carcinoma (PC) is important due to potential therapeutic and prognostic implications. However, this can be a diagnostic challenge when there is limited tissue and in poorly differentiated tumors. We evaluated the diagnostic utility of a dual immunohistochemical stain comprising p63 and P501S (prostein), applied sequentially on a single slide and visualized by double chromogen reaction, in differentiating these two cancers. Thus far, there have been no previous studies assessing the diagnostic utility of p63 and P501S combined together as a dual immunostain in distinguishing between these two cancers. p63/P501S dual-color sequential immunohistochemical staining was performed on archival material from 132 patients with high-grade UC and 23 patients with PC, and evaluated for p63 (brown nuclear) and P501S (red cytoplasmic) expression. Both the staining intensity and percentage of positive tumor cells were assessed. p63 was positive in 119/132 of UC and negative in PC. P501S was positive in 22/23 of PC and negative in UC. The p63+/P501S- immunoprofile had 90% sensitivity and 100% specificity for UC. The p63-/P501S+ immunoprofile had 96% sensitivity and 100% specificity for PC. Our results indicate that double sequential immunohistochemical staining with p63 and P501S is highly specific and can be a useful tool in distinguishing UC from PC especially when there is limited diagnostic tissue as it can be performed on a single slide.
    Diagnostic Pathology 07/2011; 6(1):67. DOI:10.1186/1746-1596-6-67 · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fabrication of high-k embedded capacitors on printed wiring board (PWB) is limited due to the inherent low-temperature process required for organic packaging. Current dielectrics for embedded capacitors are mostly organic with insufficient dielectric constant. Integration of high-k thin films on PWB is hindered by high processing temperature of ceramics. The goal of this work, is to develop low-cost/low-temperature, aqueous/non-aqueous based processes for embedded capacitors. Hydrothermal synthesis was used for synthesis of nanograined barium titanate films. Films synthesized at 95°C on titanium foils yielded nanograined films (<80 nm grains) with higher capacitor yield in comparison to conventional hydrothermal films from Ti precursors or sputtered Ti. Films with capacitance of more than 1.0 pF/cm<sup>2</sup> and thickness of 300 nm (corresponding to a dielectric constant of above 350) were developed. Oxygen plasma treatment of hydrothermal films was found to lower the loss significantly to 0.06 from 0.28. Sol-gel technique was also explored an alternate low cost large area process for synthesis of high K low loss films. Sol-gel derived films are typically crystallized and densified at temperatures that are not compatible with organic build-up processes. This limitation has been addressed using a modified sol-gel process to deposit films on a carrier foil that was subsequently laminated onto the printed wiring board. All high-temperature processing steps required by the oxide dielectrics were performed before the embedding process. High-k barium titanate (BaTiO<sub>3</sub>) and strontium titanate (SrTiO<sub>3</sub>) thin film capacitors were synthesized on base-metal nickel (Ni) and titanium (Ti) foils as carrier. Rapid thermal processing (RTP) lowers the process time for the development of a well-crystallized titanate film to 3 minutes as opposed to the few hours of processing time required for conventional heat treatment. Capacitance densities ranging from ∼45-700 nF/cm<sup>2</sup> have been achieved by varying the film thicknesses from ∼250 to 900 nm and the heat treatment conditions. By following the RTP with a 1 hr heat treatment in nitrogen (N<sub>2</sub>) atmosphere, the dielectric loss was reduced to 0.005. These sol-gel and hydrothermal films were su- bsequently integrated onto organic boards using conventional lamination and lithography methods, followed by low-cost wet etching.
    Advanced Packaging Materials: Processes, Properties and Interfaces, 2004. Proceedings. 9th International Symposium on; 02/2004
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is well established that invasive urothelial carcinoma, involving the urinary bladder and renal pelvis, has marked propensity for divergent differentiation. In recent years, several 'variant' morphologies have been described and most have been recognized in the 2004 World Health Organization Classification. These histological variants of urothelial carcinoma have clinical significance at various levels, including diagnostic, that is, awareness of the morphological variant is essential in order to avoid diagnostic misinterpretations; prognostic for patient risk stratification; and therapeutic, where a diagnostic assignment of a particular variant may be associated with the administration of a therapy distinctive from that used in conventional invasive urothelial carcinoma. The diagnoses of micropapillary urothelial carcinoma, small-cell carcinoma, lymphoepithelioma-like carcinoma and sarcomatoid carcinoma are prime examples where treatment protocols may be different than the usual muscle-invasive bladder cancer. This review discusses the variants of urothelial carcinoma, outlining for each the diagnostic features, differential diagnostic considerations and the clinical significance.
    Modern Pathology 07/2009; 22 Suppl 2(supplement 2):S96-S118. DOI:10.1038/modpathol.2009.26 · 6.19 Impact Factor
Show more