P504S Immunohistochemical Detection in 405 Prostatic Specimens Including 376 18-Gauge Needle Biopsies

Abstract

P504S is a recently described, prostate cancer-specific gene that encodes a protein involved in the beta-oxidation of branched chain fatty acids. A recent study has shown that immunohistochemical detection of P504S gene product is a sensitive and specific marker of prostatic carcinoma in formalin-fixed, paraffin-embedded tissues. We performed a detailed analysis of P504S protein expression in a large series of prostate and bladder specimens with special emphasis on staining in specific morphologic patterns of prostatic adenocarcinoma, posthormonal and radiation therapy cases, and invasive urothelial carcinoma. A total of 366 prostate needle core biopsies from 124 patients with prostate cancer, 10 biopsies from 2 patients without prostate cancer, 28 prostatectomy specimens (16 with specific morphologic patterns, 7 posthormonal therapy and 5 postradiation therapy specimens), 5 bladder specimens with invasive urothelial carcinoma, and a single transurethral resection specimen from a patient with hormonally treated prostate cancer and invasive urothelial carcinoma were stained with P504S monoclonal antibody at a 1:250 dilution using standard heat-induced epitope retrieval and avidin-biotin technique. Extent (0, no staining; 1+, 1-10% staining; 2+, 11-50% staining; 3+, > or =51% staining) and location (luminal, subluminal, and diffuse cytoplasmic) of immunoreactivity in carcinoma and benign tissues were recorded. A total of 153 of 186 biopsies (82%) with prostatic adenocarcinoma stained for P504S. Pseudohyperplastic, atrophic, ductal, and mucinous prostatic carcinomas stained similarly, as did cases treated with hormone or radiotherapy. In 81 of 377 (21%) foci of benign prostatic tissue there was staining that was almost always focal, faint, and noncircumferential. Seminal vesicles did not stain for P504S. Five of six (83%) specimens with invasive urothelial carcinoma had 2+ staining and one case had focal staining. We conclude that immunohistochemistry for P504S has potential utility in the diagnosis of prostate cancer, including those treated by hormones and radiation. Circumferential luminal to subluminal and diffuse cytoplasmic staining is the most specific staining pattern for prostatic carcinoma and is almost never associated with benign prostatic tissue. However, a negative P504S immunostain does not automatically rule out prostate cancer, as 18% of cases were negative. Additionally, occasional benign glands, high-grade prostatic intraepithelial neoplasia, atypical adenomatous hyperplasia, and urothelial carcinoma may express P504S. Therefore, we think that P504S is best used only in conjunction with strict light microscopic correlation and preferably with high molecular weight cytokeratin immunostaining.

Diagnostic utility of a p63/α-methyl-CoA-racemase (p504s) cocktail in atypical foci in the prostate

“…This confirms the results of Beach et al, 5 who reported expression in 32% of the cases. 5 In our experience, we observed a weaker intensity of expression of p504s in high-grade prostatic intraepithelial neoplasias compared to prostatic carcinomas.…”

“…The application, in our series, of coexistent antibody again basal cells (p63) demonstrated that these glands had fewer basalstained than nonpositive p504s normal glands and led us to believe that this could be interpreted as low-grade prostatic intraepithelial neoplasia ( Figure 8). This result is not concordant with the 21% reported by Beach et al 5 Like those authors, we also observed that this expression is generally focal and is weaker than the positivity of the tumoral prostatic glands. 5 The increased AMACR expression by some normal prostatic glands could reflect upregulation of metabolic pathways of prostate glands during the carcinogenic process.…”

“…This result is not concordant with the 21% reported by Beach et al 5 Like those authors, we also observed that this expression is generally focal and is weaker than the positivity of the tumoral prostatic glands. 5 The increased AMACR expression by some normal prostatic glands could reflect upregulation of metabolic pathways of prostate glands during the carcinogenic process. 8 This finding is quite similar to that of Leav et al, 31 who found that overexpression of AMACR was present in transitional lesions Diagnostic utility of a p63/AMACR (p504s) V Molinié et al in benign hypertrophic hyperplasia nodules along the transitional zone carcinomas, and confirmed that p504s is a useful marker of neoplastic transformation in the prostate gland.…”

“…Over the past 2 years, many studies have reported extensive upregulation of AMACR at the protein and transcript levels in high-grade prostatic intraepithelial neoplasia and prostate cancer. 5,8,10 …”

“…2 The most commonly used marker is the high-molecular-weight cytokeratin (CK) 903 (34bE12) and, more recently, markers such as CK 5/6 and p63 have been proposed. [3][4][5] More recently, a-methylacyl-CoA racemase (AMACR) has been reported to be a new marker of prostate cancer. 6 Although its role in prostatic carcinogenesis is unclear, several recent studies have shown that AMACR expression is upregulated in prostatic cancer, and in immunohistochemistry, 97-100% of prostate cancers are positive for AMACR.…”