Alpha-methylacyl CoA racemase (P504S): overview and potential uses in diagnostic pathology as applied to prostate needle biopsies

Abstract

The diagnosis of prostatic adenocarcinoma remains dependent on the recognition of basic haematoxylin and eosin criteria. The discovery of alpha-methylacyl CoA racemase/P504S (AMACR/P504S) overexpression in prostate cancer represents a triumph of high throughput microarray technology, and is a powerful demonstration of how this methodology can be used to facilitate the rapid development of diagnostically relevant antibodies. Immunohistochemistry with anti-AMACR/P504S is useful for detecting prostate cancer in the full range of prostate specimens encountered in surgical pathology, be they needle biopsies, transurethral resection of prostate chips, or prostatectomies. In particular, studies to date with AMACR/P504S clearly demonstrate the ability of this marker to support a diagnosis of malignancy in prostate needle biopsies. This is particularly true when it is combined with negative staining for a basal cell marker, such as 34betaE12 or p63. Although it has limitations with respect to sensitivity and specificity, AMACR/P504S will no doubt become a standard adjunctive stain used by pathologists seeking to reach a definitive diagnosis in prostate biopsies considered to be atypical, but not diagnostic of malignancy on haematoxylin and eosin sections alone.

Figure 1

Typical pattern of immunohistochemical staining of prostatic adenocarcinoma and benign prostate glands with antibody directed against α-methylacyl CoA racemase (AMACR/P504S). (A) Haematoxylin and eosin stain. (B) Section stained with the rabbit monoclonal anti-AMACR/P504S (Zeta Corporation, Sierra Madre, California, USA). Staining was performed using a 32 minute incubation with the primary antibody (1/100 dilution) and mild CC1 antigen retrieval as part of the Ventana automated immunostaining protocol. Note the intense, circumferential, granular staining in the adenocarcinoma compared with the absence of staining in the adjacent benign glands and stroma (original magnification, ×100).

Figure 2

Small focus of prostatic adenocarcinoma on a needle biopsy. (A) Haematoxylin and eosin. (B) Immunostaining for 34βE12; note the absence of staining for basal cells within the malignant glands as compared with the adjacent benign glands. (C) Malignant glands showing intensely positive, circumferential staining for AMACR/P504S compared with negative staining in the benign glands. A–C: original magnification, ×50.

Figure 3

Another example of a small focus of prostatic adenocarcinoma on a needle biopsy. (A) Haematoxylin and eosin stained section showing adenocarcinoma with perineural invasion. (B) S-100 staining to highlight the presence of the involved nerve. (C) 34βE12 staining to show the absence of a basal cell layer. (D) α-Methylacyl CoA racemase (AMACR/P504S) staining that is restricted to the adenocarcinoma. A–D: original magnification, ×50.