α-甲酰基辅酶A消旋酶在前列腺腺癌诊断和鉴别诊断中的作用

目的观察α-甲酰基辅酶A消旋酶(α—methylacyl—CoA racemase,P504S)在前列腺腺癌的诊断和鉴别诊断中的价值。方法对前列腺腺癌及其需要鉴别的病变：前列腺上皮内瘤变、不典型腺瘤样增生、不典型小腺泡增生以及正常前列腺组织(包括萎缩的腺体)和良性增生进行光镜观察,用EnVision二步法免疫组织化学方法检测P504S、细胞角蛋白(CK)34βE12、p63在各类病变组织中的表达情况。根据P504S阳性表达部位区分其表达形式为：胞质型、腔缘型、顶端胞质型及胞膜型。结果78例前列腺腺癌中,91％(71／78)阳性表达P504S,多表现为癌细胞弥漫性胞质内阳性着色较深的颗粒状物,少数为腺腔内缘或顶端胞质内及膜表达,9％(7／78)阴性表达P504S者均为亮细胞型;前列腺上皮内瘤变(9例),不典型腺瘤样增生(6例)以及不典型小腺泡增生(2例)中均见P504S不同程度的表达;96％(65／68)的正常及良性增生前列腺组织未见P504S阳性表达;增生的基底细胞也未见P504S阳性表达。结论P504S的免疫组织化学染色对判断前列腺腺癌具有重要参考价值,若与CK34βE12或p63联合应用则更有帮助。     

前列腺不典型小腺泡增生的病理形态及临床意义

目的 探讨前列腺不典型小腺泡增生的形态学特点和临床意义。方法 收集解放军总医院病理科2004-2006年前列腺穿刺活检诊断为不典型小腺泡增生病例11例,复习HE和免疫组织化学切片,并对有不典型小腺泡增生病变的蜡块重新进行34βE12、p63和P504S免疫组织化学（SP法）染色,观察不典型小腺泡增生的组织学特点和免疫组织化学表达特点。结果 11例不典型小腺泡增生均表现为排列紧凑的小腺体,其中6例小腺泡数量在3个以下,圆形或轻度不规则形,核呈单层排列,有的细胞核之间间隔较大。细胞核普遍增大,圆形或不规则形,部分可见明显的核仁。胞质呈嗜双色性或空亮,腔缘相对平整,部分腔内可见蓝色黏液。免疫组织化学显示34βE12、p63阴性,P504S阳性或弱阳性。4例腺泡数量超过3个,圆形或轻微不规则形,细胞核轻度增大,核仁不清楚或有小核仁。34βE12及p63阴性或点状阳性,P504S弱阳性或阴性。11例患者二次穿刺活检诊断为癌的有4例,多为第一次活检中腺泡数量较少但有明确细胞异型性的病例。结论不典型小腺泡增生是一种与前列腺癌密切相关的病变,其腺体数量或细胞形态或组织结构改变不足以诊断为癌的一类病变。不典型小腺泡增生病例二次活检发现癌的几率明显高于一般的增生。     

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

Prostatic needle biopsy is the preferred method for diagnosing early prostate cancer, providing specific information. In cases of histological cancer mimics, a diagnosis of atypical small acinar proliferation suspected of but not diagnosed as malignancy can be made. In such cases, and in small focus carcinomas, pathologists use 34betaE12, cytokeratin (CK) 5/6 or p63 immunostaining to label basal cells, and alpha-methylacyl-CoA racemase (AMACR/p504s) immunostaining as a positive prostate cancer marker on two distinct slides. However, in cases of small foci, ambiguous lesions might disappear. The purpose of our study was to improve the sensitivity of a cocktail of two antibodies (p63/p504s) with a sample incubation on 260 prostatic specimens, in order to help make a decision in conjunction with standard histology and CK 5/6 immunostaining. We tested 101 small focus prostatic cancers, 104 atypical small acinar proliferation, 19 high-grade prostatic intraepithelial neoplasia, two atypical adenomatous hyperplasia and 34 benign mimics of cancer. After p63/p504s immunostaining, the final diagnoses retained were as follows: 154 prostatic cancers, 14 atypical small acinar proliferation, 30 high-grade prostatic intraepithelial neoplasia, three atypical adenomatous hyperplasia and 62 benign mimics of cancer. To differentiate malignant from benign lesions, we used the criteria of greater sensitivity to p504s/p63 (95%) than to CK 5/6 (57%) or p63 (86%), and higher specificity for p504s/p63 (95%) than for CK 5/6 (88%) or p63 (81%). With the p504s/p63 cocktail, 89% of the ambiguous lesions were classified vs 53% for CK 5/6. Combined use of the two antibodies, one (p504s) as a positive marker and the other (p63) as a negative marker, with a simple immunostaining procedure, may improve diagnostic performance, sensitivity and specificity, leading to a reduction in the risk of false negatives; this technique in cases of atypical small acinar proliferation should reduce the percentage of residual ambiguous lesions and the need for additional biopsies.     

Diagnostic usefulness of monoclonal antibody P504S in the workup of atypical prostatic glandular proliferations

We stained 37 prostate needle biopsies and 3 transurethral resections (TURP) containing atypical foci and 20 morphologically unequivocal prostate cancer biopsies, including 4 with foamy features, with P504S. Of 20 biopsies with unequivocal cancer, 18 showed variable P504S staining (sensitivity, 90%); 1 minute cancer and 1 foamy cancer lacked P504S staining. Of 40 cases with atypical foci (biopsies, 37; TURP, 3), 9 were diagnosed as high-grade prostatic intraepithelial neoplasia (HGPIN), 2 were excluded, and 29 had foci of atypical small glandular proliferation. Of these 29 cases, 7 were highly suggestive of cancer, 2 of which lacked P504S staining. In 22 cases with benign atypical foci, 11 were diagnosed as postatrophic hyperplasia (none expressed P504S) and 7 as atypical adenomatous hyperplasia (AAH; 1 showed focal weak P504S staining). Of 9 HGPIN specimens, 8 showed predominantly diffuse, moderate P504S staining. P504S has slightly lower sensitivity for detection of prostate cancer than found previously. Heterogeneous expression patterns may explain negativity in some biopsy specimens with minute cancer. In atypical small glandular proliferations, diffuse positive P504S staining in atypical glands strongly supports a cancer diagnosis, but negative staining does not exclude it. P504S seems to have low sensitivity for detecting foamy prostate cancer. Most HGPINs show diffuse moderate P504S staining. AAH may show focal P504S staining. We recommend using P504S along with morphologic examination and conventional basal cell markers.     

An analysis of the p63/alpha-methylacyl coenzyme A racemase immunohistochemical cocktail stain in prostate needle biopsy specimens and tissue microarrays

We studied the usefulness of a p63/P504S immunostain "cocktail" in evaluation of prostate biopsy specimens containing atypical acini suspicious for adenocarcinoma (AASA), high-grade prostatic intraepithelial neoplasia (HPIN), and small foci of adenocarcinoma and tested the sensitivity and specificity of the immunostain with tissue microarrays (TMAs) constructed from prostatectomy and lymphadenectomy specimens. We selected 40 cases containing a focus of adenocarcinoma (14 cases), AASA (7 cases), AASA with HPIN (7 cases), HPIN (6 cases), and atypical favor benign (6 cases). After p63/P504S immunostaining, 13 cases (33%) were reclassified: AASA with HPIN to HPIN only in 5 cases (13%), atypical favor benign to benign in 4 cases (10%), AASA to adenocarcinoma in 2 cases (5%), and atypical favor benign to AASA and atypical favor benign to HPIN in 1 case (3%) each. The diagnosis of adenocarcinoma was supported by immunostain in 14 cases. In TMA studies, the p63/P504S immunostain for adenocarcinoma and HPIN had sensitivity values of 97.2% and 86.2%, respectively, and specificity values of 99.7% and 81.6%, respectively. P504S stained 64 (74%) of 87 cores of metastatic cancers, and no p63-positive cells were identified in the metastases. The p63/P504S immunohistochemical stain is a sensitive, specific marker for prostatic adenocarcinoma and HPIN and useful in the evaluation of AASA in biopsy specimens.     

Immunohistochemical application of D2-40 as basal cell marker in evaluating atypical small acinar proliferation of initial routine prostatic needle biopsy materials

D2-40 has been recently discovered as a lymphatic endothelial cell marker, and some investigators have found that D2-40 is also expressed in myoepithelial cells of salivary gland or breast. In this study, we evaluated D2-40 expression of basal cells and applied D2-40 immunohistochemistry in the combination of P504S, cytokeratin 5, and p63 for ten lesions with atypical small acinar proliferation (ASAP) in initial prostatic needle biopsy. As a result, D2-40 was expressed in basal cells, lymphatic endothelial cells, and some stromal fibroblasts of normal prostatic tissue. Among ten ASAP lesions, the final diagnosis of seven lesions was resolved by combination immunohistochemistry. D2-40 was comparable to cytokeratin 5 and p63 as a basal cell marker, and there were no lesions that failed to provide an accurate final diagnosis using only D2-40 immunohistochemistry without cytokeratin 5 or p63. However, we found some D2-40-positive stromal fibroblasts or D2-40-positive lumen-collapsed lymphatic vessels neighboring atypical glands. Pathologists should pay attention to avoid recognizing these cells as basal cells. In conclusion, the combination of immunohistochemistry of P504S, cytokeratin 5, p63, and D2-40 may contribute to the accurate diagnosis of ASAP in the initial prostatic needle biopsy.     

Detection of prostate cancer by alpha-methylacyl CoA racemase (P504S) in needle biopsy specimens previously reported as negative for malignancy

AIMS : To investigate the possibility of detecting small focal prostatic cancer by alpha-methylacyl CoA racemase (AMACR)/P504S immunohistochemistry on needle biopsy specimens that were previously interpreted as negative for carcinoma on routine haematoxylin and eosin (H&E)-stained sections. METHODS: Prostate needle biopsy specimens (n = 793) previously interpreted as benign prostatic tissue by conventional morphology from 239 patients with prostatic cancer diagnosed in other biopsy cores taken at the same biopsy session were stained with the P504S monoclonal antibody. If a biopsy specimen stained positively, two pathologists independently reviewed the original corresponding H&E-stained sections to establish the malignant diagnosis. RESULTS: Eighty-four of the 793 biopsy specimens showed AMACR immunoreactivity; nine of these (9/793, 1.1%) contained previously unrecognized small focal prostatic carcinoma (Gleason 6, N = 8; Gleason 8, N = 1). Six of nine (67%) carcinomas showed foamy/pseudohyperplastic (N = 3) or atrophic (N = 3) features. Additionally, five biopsy specimens (5/793, 0.6%) with positive AMACR staining that did not meet the criteria for prostatic cancer on the original H&E slides were considered to be atypia. CONCLUSIONS: In this study, we found a 1.1% false-negative rate for carcinoma on routine H&E-stained sections. AMACR immunohistochemical staining has shown the ability to improve detection of small focal prostatic carcinoma that could be missed by conventional histological examination.     

Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens

We assessed the usefulness of immunohistochemical analysis with a 3-antibody cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63) and a double-chromogen reaction for detection of limited prostate cancer in 138 needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma and 56 benign prostates. When carcinoma was present, red cytoplasmic granular staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63) and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78 (95%) expressed AMACR; all malignant glands were negative for basal cell staining. All benign glands adjacent to malignant glands were recognized easily by basal cell marker positivity and little or no AMACR expression. No benign glands were simultaneously positive for AMACR and negative for basal cell markers (specificity, 100%). There were no differences in intensity and numbers of positive glands with double-chromogen staining compared with using 1-color staining. Our results indicate that immunohistochemistry with a 3-antibody cocktail and double chromogen is a simple and easy assay that can be used as a routine test, which overcomes the problems of studying small lesions in prostate needle biopsies with multiple immunohistochemical stains.     

153例经直肠前列腺穿刺活检病例临床病理及免疫组化分析

目的:对经直肠前列腺穿刺活检病例的临床资料、病理形态学及免疫组化进行分析,以提高对前列腺癌的临床及病理诊断准确率.方法:回顾性分析我院2006年1月~2011年6月间153例行前列腺穿刺活检病人的临床及病理资料,研究其血清PSA、病理形态学特点,并将其中确诊为前列腺癌患者50例与良性前列腺病变患者103例进行对比分析....     

Analysis of alpha-methylacyl-CoA racemase (P504S) expression in high-grade prostatic intraepithelial neoplasia

Alpha-methylacyl-CoA racemase (AMACR), also known as P504S, is a recently identified molecular marker for prostate cancer. The expression of AMACR/P504S has also been observed in high-grade prostatic intraepithelial neoplasia (PIN), a precursor lesion of prostate cancer. However, a detailed study focusing on the analysis of AMACR/P504S expression in high-grade PIN has not been performed. In this study, we analyzed AMACR/P504S expression by immunohistochemistry in 3954 prostatic ducts and acini with high-grade PIN from 140 prostatectomy specimens. AMACR/P504S immunoreactivity was measured as negative (0), weakly positive (+1), moderately positive (+2), and strongly positive (+3). AMACR/P504S immunoreactivity was detected in 90.0% (126/140) of high-grade PIN cases, although only 41.5% (1642/3954) of prostatic glands involved by PIN showed AMACR/P504S immunoreactivity. A significantly higher AMACR/P504S-positive rate (56.0%) was found in isolated high-grade PIN glands adjacent to cancer (distance less than 5 mm) compared with those away from cancer (distance more than 5 mm; 14%, P < 0.0001). High-grade PIN glands adjacent to cancer also showed a higher (P < 0.0004) AMACR/P504S intensity (1.62) than did those away from cancer (1.11). Our results suggest that PIN strongly positive for AMACR/P504S might be more closely associated with cancer than PIN negative or weakly positive for AMACR/P504S. This study provides additional evidence to link high-grade PIN as a precursor lesion to prostatic adenocarcinoma.     

Diagnostic utility of alpha-methylacyl CoA racemase (P504S) on prostate needle biopsy

Alpha-methylacyl CoA racemase (AMACR), also known as P504S, was identified by the analysis of cDNA library subtraction in conjunction with high throughput microarray screening from prostate tissue and has been proven to be one of the very few biomarkers that can distinguish cancer from benign cells with high sensitivity and specificity for prostate carcinoma. It is a successful example of the translation of molecular findings into clinical practice. This review focuses on the study of AMACR (P504S) expression in small focal prostate cancer and atypical small acinar proliferation (ASAP) on needle biopsies and emphasizes the utility of AMACR (P504S) in routine surgical pathology practice. We also discuss the potential pitfalls and caveats in the interpretation of immunostaining results.     

Utility of immunohistochemistry for alpha-methylacyl-CoA racemase in distinguishing atrophic prostate cancer from benign atrophy

Small atrophic prostate cancers on needle biopsy are rare and difficult to distinguish from benign atrophy on needle biopsy. We report on a study of 23 needle biopsy specimens with small foci of atrophic prostate cancer from the consult service of one of the authors. In 19 cancer cases the atrophic component was pure; in 4 cases it was dominant with a minor (<5%) nonatrophic cancer component. These atrophic cancers and 16 cases of florid benign atrophy on needle biopsy were examined by immunohistochemistry for alpha-methylacyl-CoA-racemase (AMACR). All cases of cancer and atrophy were verified immunohistochemically with antibodies to basal cells (34betaE12 and p63). AMACR staining were scored as 1+ (5% to 25% of glands expressing AMACR), 2+ (26% to 50% of glands expressing AMACR), or 3+ (>50% of glands expressing AMACR). Positive staining was defined as staining above that of surrounding benign glands. AMACR was expressed in 69.6% of atrophic prostate cancers (3+, 11 cases; 2+, 3 cases; 1+, 2 cases); 30.4% (7 cases) of atrophic prostate cancer exhibited no AMACR expression. In the 4 cases with a few glands of ordinary (nonatrophic) prostate cancer, the nonatrophic cancer demonstrated more intense and a greater extent of AMACR staining. Fourteen cases (87.5%) of benign atrophy showed no AMACR expression. In 2 cases (12.5%) of benign atrophy, background immunostaining made it difficult to assess AMACR expression. We conclude that AMACR immunostaining alone is not sufficiently discriminatory in the differential diagnosis of atrophic prostate cancer versus benign atrophy. Atrophic prostate cancers are not as frequently or as strongly positive as ordinary prostate cancer. Using a panel of immunostains including AMACR, 34betaE12 and p63 (positive AMACR immunostaining along with negative basal cell markers) is recommended in the differentiation of atrophic prostate cancer and benign atrophy.     

Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia.

Typically glands of prostatic adenocarcinoma have a single cell lining, although stratification can be seen in invasive carcinomas with a cribriform architecture, including ductal carcinoma. The presence and diagnostic significance of stratified cells within non-cribriform carcinomatous prostatic glands has not been well addressed. The histomorphological features and immunohistochemical profile of cases of non-cribriform prostatic adenocarcinoma with stratified malignant glandular epithelium were analyzed. These cases were identified from needle biopsy cases from the consultation files of one of the authors and from a review of 150 consecutive in-house needle biopsy cases of prostatic adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive against high molecular weight cytokeratin (34betaE12), p63 and alpha-methylacyl-coenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from the 150 consecutive in-house cases (1.3%). In 4 cases, the focus with glands having stratified epithelium was the sole carcinomatous component in the biopsy, while such a component represented 5-30% of the invasive carcinoma seen elsewhere in the remaining cases. The main attribute in all these foci was the presence of glandular profiles lined by several layers of epithelial cells with cytological and architectural features resembling flat or tufted high-grade prostatic intraepithelial neoplasia, but lacking basal cells as confirmed by negative 34betaE12 and/or p63 immunostains in all cases. The AMACR staining profile of the stratified foci was variable, with 4 foci showing positivity, and 3 foci being negative, including two cases that displayed AMACR positivity in adjacent non-stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified malignant glandular epithelium can be identified in prostate needle biopsy samples harboring non-cribriform prostatic adenocarcinoma and resembles glands with high-grade prostatic intraepithelial neoplasia. These 'PIN-like' carcinomas can present in pure form. Recognition of this pattern of prostatic adenocarcinoma is necessary to correctly diagnose such cases as invasive carcinoma.     

AMACR/34βE12/p63鸡尾酒双染对诊断前列腺癌及癌前病变的价值

目的探讨AMACR／34βE12／p63鸡尾酒双染对诊断小灶性前列腺癌及癌前病变的价值。方法从2005年6月起对3个月内临床连续送检的105例前列腺穿刺活检标本,6例前列腺癌根治标本和19例经尿道和耻骨上摘除的良性前列腺增生标本总计130个病例,1030个组织块中需要用免疫组织化学辅助诊断的262个组织块分别作AMACR／34βE12／p63鸡尾酒双染,同时作这3个抗体的单项染色,并结合HE切片和临床资料观察结果作出诊断。结果鸡尾酒双染切片中前列腺癌和高级别上皮内瘤变（HGPIN）上皮细胞呈蓝黑色,良性腺体的基底细胞呈红色。癌的蓝黑色腺上皮周围无红色基底细胞围绕,HGPIN的蓝黑色腺上皮周围有间断或连续的红色基底细胞。共在214个（82％）组织块中发现前列腺癌,包括31处小灶性癌。64个（24％）组织块中发现HGPIN,包括局灶性HGPIN和小腺泡性HGPIN。1个组织块有不典型性腺瘤样增生。未发现上皮细胞AMACR阳性同时基底细胞34βE12和p63阴性的良性腺体。结论鸡尾酒双染有助于提高小灶性前列腺癌和HGPIN检出率。     

Alpha-methylacyl coenzyme A racemase immunoreactivity in partial atrophy of the prostate

It was reported that 15 of 19 consultation cases of prostatic partial atrophy were a-methylacyl coenzyme A racemase (AMACR)-positive. We investigated partial atrophy cases from a single institution using a standard AMACR immunostaining method. Immunohistochemical analysis was performed using an antibody cocktail containing p63, high-molecular-weight keratin (34bE12), and AMACR antibodies on 122 foci of partial atrophy. AMACR staining was analyzed in partial atrophy (n = 122) and compared with adjacent benign glands (n = 122) and prostatic carcinomas (n = 28). Of 122 foci of partial atrophy, 38 (31.1%) showed AMACR immunoreactivity. Typically, AMACR staining was weak or moderate. In addition, 82 (67.2%) showed patchy to negative distribution of basal cells. Partial atrophy may show AMACR immunoreactivity when using a 34bE12, p63, and AMACR antibody cocktail staining method. Compounding this problem, focal lack of basal cells may be seen. However, the AMACR staining pattern of partial atrophy is usually comparable to that of adjacent benign glands and substantially different from adenocarcinoma.     

The significance of the P504S expression pattern of high-grade prostatic intraepithelial neoplasia (HGPIN) with and without adenocarcinoma of the prostate in biopsy and radical prostatectomy specimens

Diagnosis of prostatic adenocarcinoma is usually not difficult in biopsy specimens. Problems may occur in biopsy specimens, containing only a few suspicious lesions. Recently, P504S has been tested as a new marker for prostatic carcinoma. When over-expressed in atypical glands without basal cells, it establishes the diagnosis of prostatic carcinoma. We analysed the staining intensity of P504S in 208 biopsy specimens from prostates (1) with adenocarcinoma (n=132), (2) with high-grade prostatic intraepithelial neoplasia (HGPIN) with adenocarcinoma (n=36), (3) with HGPIN alone (n=40) and in radical prostatectomy specimens with HGPIN adjacent to (n=54) or distant from adenocarcinoma (n=64). P504S expression was negative to weakly positive in biopsy specimens showing HGPIN without carcinoma and weakly positive in radical prostatectomy specimens revealing HGPIN distant from adenocarcinoma. In biopsy specimens with a combination of HGPIN and adenocarcinoma and in radical prostatectomy specimens with HGPIN adjacent to adenocarcinoma, P504S was strongly expressed. The same findings were made in radical prostatectomy specimens containing adenocarcinoma and HGPIN adjacent to or distant from adenocarcinoma and in preoperative biopsies revealing adenocarcinoma and HGPIN. These results suggest that moderate to strong P504S expression in HGPIN of biopsy specimens is indicative of an associated adenocarcinoma and may be helpful in the choice of therapy.     

Comparison of monoclonal antibody (P504S) and polyclonal antibody to alpha methylacyl-CoA racemase (AMACR) in the work-up of prostate cancer

AIM: Studies using a monoclonal (P504S) and a polyclonal antibody (p-AMACR) to alpha-methylacyl-CoA racemase (AMACR) have shown variable expression in prostate cancer (PCa). The goal is to compare the sensitivity of both antibodies in PCa and evaluate their utility in the work-up of atypical prostate needle biopsies (NBXs). METHODS AND RESULTS: A tissue microarray (TMA) with 248 samples of benign prostate, high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa samples, 20 NBXs with minute PCa and 32 NBXs with 'atypical' foci were stained with P504S and p-AMACR. Ninety percent of PCa (76/76 TMA, 16/20 NBXs) showed predominantly strong p-AMACR expression while 87% (65/69 TMA, 16/20 NBXs) showed variable P504S expression (sensitivity 90% versus 87%, P = 0.10). In HGPIN, P504S and p-AMACR were positive in 77% and 91% of samples, respectively. In the 'atypical' NBXs group, 53% were classified as PCa, 12% benign and 35% atypical, suspicious for PCa, after review of the basal marker. Of atypical, suspicious for PCa, P504S/p-AMACR helped convert the diagnosis to PCa in 5/11 (45%) cases, where, despite negative basal cell markers, morphology was less than optimal. CONCLUSIONS: Differences between P504S and p-AMACR appear marginal and clinically insignificant. AMACR is negative in a subset of unequivocal minute PCa with both antibodies. However, when utilized in proper context, AMACR may offer significant advantage in converting an 'atypical' diagnosis to PCa where morphology and basal markers are less than optimal in resolving the diagnosis.     

Sensitivity of P504S/alpha-methylacyl-CoA racemase (AMACR) immunohistochemistry for the detection of prostate carcinoma on stored needle biopsies.

Alpha methylacyl-CoA-racemase (AMACR), also known as P504S, has been widely used as a positive marker for the diagnosis of prostate carcinoma in clinical practice. The utility of this assay is highly dependent on the sensitivity of AMACR detection in routinely processed biopsies. It is common practice to store precut prostate biopsy sections. Hence, it is important to determine the effect on the immunoreactive of P504S/AMACR in stored, unstained glass slides as compared with freshly cut sections of paraffin-embedded tissue. The purpose of this study was to determine the sensitivity of AMACR immunostaining for the detection of prostate carcinoma on stored needle biopsies. A total of 63 prostate biopsies with prostate carcinoma were transferred onto glass slides, baked, and stored for 1.6 to 9.2 months. The Gleason scores were 3+3(6) (n=40) including 10 small focal carcinomas (< or = 1.0 mm), 4+3(7) (n=16), and 4+4(8) or higher (n=7). The slides were then stained with a monoclonal antibody to P504S, and the staining intensity was compared with sections cut from the same blocks just prior to immunostaining, without an intervening storage period. There was no loss of sensitivity of AMACR for prostate adenocarcinoma, regardless of the length of the storage interval. The sensitivity was preserved and was independent of Gleason scores. The sensitivity of AMACR for small foci of adenocarcinoma was also not affected by the length of storage. Overall, stored slides had no observable increase in nonspecific background staining over freshly cut sections. These results indicate that the time interval between mounting and staining does not affect the sensitivity of the AMACR immunohistochemistry (IHC) stain in the detection of prostate cancer even with small foci of carcinoma on needle biopsies.     

Immunohistochemical detection of P504S in primary and metastatic renal cell carcinomas.

P504S/alpha-methylacryl CoA racemase has been shown to be a relatively sensitive and specific positive marker for prostatic adenocarcinoma. The potential utility of P504S in renal cell neoplasms has not been explored in a large series. We assessed the diagnostic value of P504S in 332 cases of nonprostatic neoplasms using the avidin-biotin-peroxidase complex technique, including 115 renal neoplasms, 28 metastatic renal cell carcinomas (RCCs), and 189 nonrenal neoplasms. The results demonstrated that a granular, cytoplasmic staining pattern for P504S was observed in 48 of 70 (68.6%) conventional (clear cell) RCCs, 15 of 15 (100%) papillary RCCs, 2 of 7 (29%) chromophobe RCCs, and 2 of 8 (25%) oncocytomas. Among the 70 cases of clear cell RCC, positivity of P504S was seen in 40%, 71%, 94%, and 75% of RCCs with Furhman nuclear grade I, II, III, and IV, respectively. Strong immunostaining was present in each case (86/86) in the proximal tubules adjacent to the renal neoplasm. Eighty-two percent of metastatic RCCs (23/28) were positive for P504S. However, only 24 of 189 (13%) nonrenal malignancies were positive. The 24 positive cases included 12 of 13 (92%) colorectal adenocarcinomas, 6 of 30 (20%) ductal carcinomas of the breast, and 4 of 23 (17%) adenocarcinomas of the lung. These findings suggest that P504S is a useful marker in diagnosing primary and metastatic RCCs, although it has little value in differentiating chromophobe RCC from oncocytoma.     

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

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.