Prostate cancer is the second most common cause of cancer and the sixth leading cause of cancer death among men worldwide, To diagnose prostate cancer, no specific single histologic feature is sufficiently available. It is a challenging task to accurately diagnose small foci of prostate cancer for pathologists and to distinguish cancer from its benign mimickers. Establishing a definitive diagnosis of malignancy in prostate needle biopsies with very little foci of adenocarcinoma is a major diagnostic challenge for pathologists. A positive diagnostic marker specific for prostatic adenocarcinoma may enhance the ability to detect limited prostate cancer and reduce errors in diagnosis. The recent discovery of the overexpression of P504S/α-Methylacyl coenzyme A racemase (AMACR) in prostate cancer is a successful example of translating an advanced molecular finding into clinical practice. AMACR (P504S) has been proven to be one of the few biomarkers that can help distinguish cancer from benign cells, with high sensitivity and specificity for prostate carcinoma. This study focuses on the study of AMACR (P504S) expression in prostate cancer, premalignant lesions, benign prostate tissues, and other normal and malignant tissues and a discussion of its clinical usefulness. We recommend the interpretation of the AMACR immunohistochemical results in routine surgical pathology practice and also discuss the potential future applications of this marker in diagnosis of various lesions

Alpha-methylacyl-coenzyme A racemase (AMACR; P504S) is a mitochondrial and peroxisomal enzyme involved in the metabolism of branched-chain fatty acid and bile acid intermediates. Recently, AMACR has been demonstrated to be overexpressed in localized and metastatic prostate cancer and in high-grade prostatic intraepithelial neoplasia but not in normal prostatic glands, suggesting that it may be an important tumor marker. This study examines AMACR expression in a variety of human cancers to assess its viability as a tumor marker in the clinical setting. Two hundred sixty-three cancers from different sites were examined in three multitumor tissue micro arrays, which included two or three tissue cores (1.0 mm in diameter) from each neoplastic and normal tissue specimen. Cancers studied included breast (94 cases), prostate (38), lung (28), endometrium (27), colon (29), ovary (26), and melanoma (21). Normal tissues in the microarray were prostate (15), lung (6), endometrium (5), colon (4), ovary (2), and skin (3). Sections were immunostained, after prior pressure cooker antigen retrieval, using rabbit monoclonal AMACR antibody (1:40) (Zeta Corp, Sierra Madre, CA) and horseradish peroxidase-labeled polymer conjugated secondary antibody (Envision, Dako, Carpinteria, CA). A section of prostate cancer and prostatic intraepithelial neoplasia was used as positive control. Protein expression was scored as negative, weak (faint cytoplasmic or granular apical staining), moderate (diffuse granular cytoplasmic stain), and strong (diffuse intense cytoplasmic stain). Only moderate and strong staining was considered as positive staining, based on prior work. AMACR protein overexpression was found in several cancers, including prostate (34/38 [89.5%]), colon (13/29 [44.8%]), lung (4/28 [14.3%]), melanoma (2/21 [9.5%]), endometrium (2/27 [7.4%]), and breast (3/94 [3.2%]). None of the ovarian cancers (26 cases) demonstrated AMACR overexpression. AMACR expression was not present in any of the normal tissues nor in benign prostatic tissue associated with prostate carcinomas. This study suggests that AMACR is potentially an important tumor marker, particularly for prostate and colon cancer. It may be a useful adjunct to an immunohistochemical panel employed in the differential diagnosis of colon versus ovarian and breast carcinoma; the latter two infrequently express AMACR.

Introduction: The spectrum of diseases affecting the prostate gland in men can be inflammatory, benign, premalignant lesions and malignancy. Major diagnostic challenge of surgical prostate biopsy interpretation is either due to a small focus of cancer or presence of various benign mimickers of malignancy which is labeled as suspicious foci. Aim of the study was to evaluate complete histopathological spectrum of lesions encountered on transrectal ultra sonography (TRUS) guided prostate needle biopsy and transurethral resection of prostate (TURP) chips and to use immunohistochemistry (IHC) markers like Alpha-methylacyl-Co enzyme A racemase (AMACR) and p63 as an adjunct in resolving the suspicious cases. Materials and Methods: We assessed total 60 cases of prostatic specimens received during December 2015 to November 2017. The received specimens were routinely processed and histopathological examination was carried out. IHC for AMACR and p63 was performed and results were analyzed using SPSS software. Results: Majority of cases were benign prostatic hyperplasia (BPH) (73.3%). Incidence of prostate cancer was low (16.6%). After IHC, out of the six (10%) histomorphologically suspicious cases, three cases were positive for only AMACR; two cases were positive for only p63 and one case showed positivity for both. Immunohistochemistry with AMACR and p63 proved to be highly sensitive markers for detecting malignancy but AMACR marker showed less specificity. Conclusion: Histomorphologically, benign lesions of prostate are more common than malignant ones. Combination of AMACR and p63 IHC enhances the diagnostic accuracy in suspicious cases by identifying premalignant lesions or malignancy and reduces misdiagnosis.

P504S is a prostate cancer specific gene that encodes for α-methylacyl CoA racemase (AMACR). AMACR has been shown to be selectively over expressed in prostatic adenocarcinoma with minimal to undetectable expression in benign prostatic tissue. We studied the expression of AMACR in 30 cases of prostatic adenocarcinoma using polyclonal anti-AMACR antibody and correlated it with Gleason score. Extent of staining/proportion score (0: no positive cells; 1+:1-10% positive cells; 2+11-50% positive cells; 3+>50% positive cells) was also recorded and correlated with Gleason score. All the 30 cases showed strong, cytoplasmic granular AMACR staining irrespective of their Gleason score with 26 (86.7%) cases showing immunostaining in more than 50% tumor cells (3+ proportion score). Benign prostate tissue adjacent to adenocarcinoma showed negative AMACR staining. No correlation was seen between Gleason score and AMACR proportion score. We concluded that AMACR is a highly sensitive positive marker of prostatic adenocarcinoma.