α-Methylacyl-CoA Racemase from Mycobacterium tuberculosis-Detailed Kinetic and Structural Characterization of the Active Site.

α-Methylacyl-CoA racemase in M. tuberculosis (MCR) has an essential role in fatty acid metabolism and cholesterol utilization, contributing to the bacterium's survival and persistence. Understanding the enzymatic activity and structural features of MCR provides insights into its physiological and pathological significance and potential as a therapeutic target. Here, we report high-resolution crystal structures for wild-type MCR in a new crystal form (at 1.65 Å resolution) and for three active-site mutants, H126A, D156A and E241A, at 2.45, 1.64 and 1.85 Å resolutions, respectively. Our analysis of the new wild-type structure revealed a similar dimeric arrangement of MCR molecules to that previously reported and details of the catalytic site. The determination of the structures of these H126A, D156A and E241A mutants, along with their detailed kinetic analysis, has now allowed for a rigorous assessment of their catalytic properties. No significant change outside the enzymatic active site was observed in the three mutants, establishing that the diminution of catalytic activity is mainly attributable to disruption of the catalytic apparatus involving key hydrogen bonding and water-mediated interactions. The wild-type structure, together with detailed mutational and biochemical data, provide a basis for understanding the catalytic properties of this enzyme, which is important for the design of future anti-tuberculosis drug molecules.

Analysis of enzyme reactions using NMR techniques: A case study with α-methylacyl-CoA racemase (AMACR).

α-Methylacyl-CoA racemase (AMACR; P504S) catalyzes the conversion of R-2-methylacyl-CoA esters into their corresponding S-2-methylacyl-CoA epimers enabling their degradation by ß-oxidation. The enzyme also catalyzes the key epimerization reaction in the pharmacological activation pathway of ibuprofen and related drugs. AMACR protein levels and enzymatic activity are increased in prostate cancer, and the enzyme is a recognized drug target. Key to the development of novel treatments based on AMACR inhibition is the development of functional assays. Synthesis of substrates and purification of recombinant human AMACR are described. Incubation of R- or S-2-methylacyl-CoA esters with AMACR in vitro resulted in formation of epimers (at a near 1-1 ratio at equilibrium) via removal of their α-protons to form an enolate intermediate followed by reprotonation. Conversion can be conveniently followed by incubation in buffer containing 2H2O followed by 1H NMR analysis to monitor conversion of the α-methyl doublet to a single peak upon deuterium incorporation. Incubation of 2-methylacyl-CoA esters containing leaving groups results in an elimination reaction, which was also characterized by 1H NMR. The synthesis of substrates, including a double labeled substrate for mechanistic studies, and subsequent analysis is also described.

Radiomics-Based Machine Learning Models for Predicting P504s/P63 Immunohistochemical Expression: A Noninvasive Diagnostic Tool for Prostate Cancer.

Objective: To develop and validate a noninvasive radiomic-based machine learning (ML) model to identify P504s/P63 status and further achieve the diagnosis of prostate cancer (PCa). Methods: A retrospective dataset of patients with preoperative prostate MRI examination and P504s/P63 pathological immunohistochemical results between June 2016 and February 2021 was conducted. As indicated by P504s/P63 expression, the patients were divided into label 0 (atypical prostatic hyperplasia), label 1 (benign prostatic hyperplasia, BPH) and label 2 (PCa) groups. This study employed T2WI, DWI and ADC sequences to assess prostate diseases and manually segmented regions of interest (ROIs) with Artificial Intelligence Kit software for radiomics feature acquisition. Feature dimensionality reduction and selection were performed by using a mutual information algorithm. Based on screened features, P504s/P63 prediction models were established by random forest (RF), gradient boosting decision tree (GBDT), logistic regression (LR), adaptive boosting (AdaBoost) and k-nearest neighbor (KNN) algorithms. The performance was evaluated by the area under the ROC curve (AUC) and accuracy. Results: A total of 315 patients were enrolled. Among the 851 radiomic features, the 32 top features were derived from T2WI, in which the gray-level run length matrix (GLRLM) and gray-level cooccurrence matrix (GLCM) features accounted for the largest proportion. Among the five models, the RF algorithm performed best in general evaluations (microaverage AUC=0.920, macroaverage AUC=0.870) and provided the most accurate result in further sublabel prediction (the accuracies of label 0, 1, and 2 were 0.831, 0.831, and 0.932, respectively). In comparative sequence analyses, T2WI was the best single-sequence candidate (microaverage AUC=0.94 and macroaverage AUC=0.78). The merged datasets of T2WI, DWI, and ADC yielded optimal AUCs (microaverage AUC=0.930 and macroaverage AUC=0.900). Conclusions: The radiomic-based RF classifier has the potential to be used to evaluate the presurgical P504s/P63 status and further diagnose PCa noninvasively and accurately.

Performance comparison of anti-p504s (SP116) Rabbit Monoclonal Primary Antibody vs. Monoclonal Rabbit Anti-Human AMACR clone 13H4 when duplexed with VENTANA Basal Cell Cocktail (34ßE12+p63) as a diagnostic aid for prostatic adenocarcinoma using immunohistochemistry.

Alpha-methylacyl-coenzyme A-racemase (AMACR), also known as p504s, is overexpressed in prostatic adenocarcinoma and is frequently used in combination with basal cell markers to aid in diagnosing difficult prostate adenocarcinoma cases. In this retrospective method comparison study, we examined the sensitivity and specificity of the ready-to-use anti-p504s (SP116) Rabbit Monoclonal Primary Antibody compared to the monoclonal rabbit anti-human AMACR clone 13H4 in prostatic adenocarcinoma samples. De-identified prostatic adenocarcinoma tissue samples were stained with either the SP116 or 13H4 antibody clone in combination with the VENTANA Basal Cell Cocktail (34ßE12+p63) and scored as positive or negative for prostatic adenocarcinoma. The scoring pathologist was blinded to the known historical diagnosis of each sample. The scoring pathologist correctly diagnosed each sample regardless of which p504s clone was used. Both assays using either clone were 100% concordant in their sensitivity and specificity. This study demonstrates that the ready-to-use anti-p504s (SP116) Rabbit Monoclonal Primary Antibody is equivalent to clone 13H4 concentrate when used according to package insert instructions in combination with the VENTANA Basal Cell Cocktail (34ßE12+p63) to aid pathologists in the diagnosis of prostatic adenocarcinoma.

Rarest of the Rare Metastatic Tubulocystic Carcinoma of Kidney.

Tubulocystic carcinoma of the kidney is a rare neoplasm with <100 case reports. Patients are usually asymptomatic and have a relatively indolent disease course occurring predominantly in males. These tumors rarely metastasize. It was previously considered to have some similarities to various other renal cancers, although this tumor has distinct macroscopic, microscopic, and immunohistochemical features. It is now a well-established entity in renal neoplastic pathology. Herein we present a case of metastatic tubulocystic carcinoma presenting with bony metastasis.

The auxiliary diagnostic value of prostate-specific antigen and α-methylacyl-CoA racemase in prostate cancer.

Prostate cancer (PCa) is one of the most common types of malignant tumor, which places a major burden on the health of men, worldwide. A prerequisite to ensure good treatment outcomes for patients with PCa is an accurate diagnosis. The present study aimed to investigate the diagnostic value of prostate-specific antigen (PSA) and α-methylacyl-CoA racemase (P504S) in PCa, using the tumor-associated immunolabels. In total, clinical data was collected from 125 patients undergoing prostate biopsy or surgery between January 2015 and September 2019, and stratified into: PCa (45), benign prostatic hyperplasia (BPH) (60) and unconfirmed diagnosis (20). Immunohistochemistry analysis was performed to assess PSA and P504S expression levels in each group compared with that in the controls (the normal tissue in each group was the internal control). The results demonstrated that the expression level of P504S was significantly higher in the PCa group compared with that in the BPH group. Furthermore, no significant association was observed in the PCa group between PSA and P504S expression levels, and the Gleason grading groups. A total of 20 unconfirmed diagnoses was verified via PSA/P504S. Taken together, the results suggest that combination PSA and P504S have a positive effect in identifying prostate cancer. However, PSA and P504S still have limitations in their diagnosis and the final results need to be carefully and comprehensively analyzed, thus further studies are required to determine their diagnostic values.

Expression of alpha-methylacyl-CoA racemase in vaginal gastric-type adenocarcinoma and uterine clear cell carcinoma.

BACKGROUND: Alpha-methylacyl-coenzyme A racemase (AMACR, P504S) is a commonly used marker in immunohistochemical diagnosis of prostate cancer. Recent studies identified P504S markers of the clear cell histotype in the ovary and/or endometrium. Gastric-type adenocarcinoma (GAS) is difficult to diagnose histologically, particularly when there is crossover with clear cell carcinoma (CCC). However, the significance of P504S for differentially diagnosing GAS and CCC is unclear. AIM: To evaluate P504S as a potential diagnostic marker of GAS and CCC. SETTINGS AND DESIGN: We analyzed P504S expression in 48 cervical carcinomas (32 GAS and 16 CCC), as well as the expression of other markers including hepatocyte nuclear factor-1 beta (HNF-1ß) and NapsinA. MATERIAL AND METHODS: The expression differences of HNF-1ß, NapsinA, and P504S in GAS and CCC were detected by immunohistochemistry. Immunohistochemical histoscores based on the intensity and extent of staining were calculated. RESULTS: The positive rates of HNF-1ß in GAS and CCC were 90.32% and 75%, respectively. (χ2 = 2.251, P = 0.663). The positive rates of NapsinA in GAS and CCC were 19.36% and 81.25%, respectively. (χ2 = 47.332, P < 0.01). The positive rates of P504S in GAS and CCC were 16.13% and 81.25%, respectively. (χ2 = 41.420, P < 0.01). HNF-1ß was frequently expressed in GAS and CCC, while NapsinA and P504S were frequently expressed in CCC, and reduced or lost in GAS. CONCLUSION: NapsinA and P504S can be used to differentiate between GAS and CCC.

Novel 2-arylthiopropanoyl-CoA inhibitors of α-methylacyl-CoA racemase 1A (AMACR; P504S) as potential anti-prostate cancer agents.

α-Methylacyl-CoA racemase (AMACR; P504S) catalyses an essential step in the degradation of branched-chain fatty acids and the activation of ibuprofen and related drugs. AMACR has gained much attention as a drug target and biomarker, since it is found at elevated levels in prostate cancer and several other cancers. Herein, we report the synthesis of 2-(phenylthio)propanoyl-CoA derivatives which provided potent AMACR inhibitory activity (IC50 = 22-100 nM), as measured by the AMACR colorimetric activity assay. Inhibitor potency positively correlates with calculated logP, although 2-(3-benzyloxyphenylthio)propanoyl-CoA and 2-(4-(2-methylpropoxy)phenylthio)propanoyl-CoA were more potent than predicted by this parameter. Subsequently, carboxylic acid precursors were evaluated against androgen-dependent LnCaP prostate cancer cells and androgen-independent Du145 and PC3 prostate cancer cells using the MTS assay. All tested precursor acids showed inhibitory activity against LnCaP, Du145 and PC3 cells at 500 µM, but lacked activity at 100 µM. This is the first extensive structure-activity relationship study on the influence of side-chain interactions on the potency of novel rationally designed AMACR inhibitors.

Identification of novel small-molecule inhibitors of α-methylacyl-CoA racemase (AMACR; P504S) and structure-activity relationships.

α-Methylacyl-CoA racemase (AMACR; P504S; EC 5.1.99.4) catalyses epimerization of 2-methylacyl-CoAs and is important for the degradation of branched-chain fatty acids and the pharmacological activation of ibuprofen and related drugs. It is also a novel drug target for prostate and other cancers. However, development of AMACR as a drug target has been hampered by the difficulties in assaying enzyme activity. Consequently, reported inhibitors have been rationally designed acyl-CoA esters, which are delivered as their carboxylate prodrugs. The novel colorimetric assay for AMACR based on the elimination of 2,4-dinitrophenolate was developed for high-throughput screening and 20,387 'drug-like compounds' were screened, with a throughput of 768 compounds assayed per day. Pyrazoloquinolines and pyrazolopyrimidines were identified as novel scaffolds and investigated as AMACR inhibitors. The most potent inhibitors have IC50 values of ~2 µM. The pyrazoloquinoline inhibitor 10a displayed uncompetitive inhibition, whilst 10j displayed mixed competitive inhibition. The pyrazolopyrimidine inhibitor 11k displayed uncompetitive inhibition. This is the first report of the identification of specific drug-like small-molecule AMACR inhibitors by high-throughput screening. Pyrazoloquinolines and pyrazolopyrimidines may also be useful as inhibitors of other CoA-utilizing enzymes.

A Rare Case of Liver Metastasis from Prostate Cancer Mimicking Hepatocellular Carcinoma on Immunohistochemistry: Role of F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Diagnosis.

We present a case with space-occupying lesion in cirrhotic liver, diagnosed as hepatocellular carcinoma on immunohistochemistry, who underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and showed FDG-avid lesions in liver as well as in the prostate. These findings guided in establishing the diagnosis of prostate cancer, metastasizing to liver by performing additional immunohistochemical markers. PET/CT was also useful in identifying coexisting non-Hodgkin's lymphoma.

[Multi-modality MRI parameters correlate with the expression of the P504s protein in prostate cancer].

OBJECTIVE: To evaluate the expressions of P504s, 34ß-E12, and P63 proteins in PCa and the correlation between the parameters of multi-modality MRI and the expression of P504s. METHODS: We retrospectively analyzed the multi-modality MRI data on 43 PCa and 64 non-PCa patients. We obtained the signal intensity-time (SI-T) curves, maximum SI (SImax), time to SImax (Tmax), rate of maximum enhancement (Rmax), and automatically generated apparent diffusion coefficient (ADC) values by conventional, diffusion-weighted and dynamic contrast-enhanced MRI, and determined the expressions of P504s, 34ß-E12 and P63 in the prostatic tissues of the patients by immunohistochemistry. RESULTS: Statistically significant differences were observed between the PCa and non-PCa groups in the positive expressions of P504s (83.7% vs 0%, P < 0.05), 34ß-E12 (25.6% vs 91.0%, P < 0.05) and P63 (25.6% vs 86.0%, P < 0.05) in the prostatic tissue, the ADC value (ï¼»0.83 ± 0.22ï¼½ vs ï¼»1.34 ± 0.28ï¼½ ×10－3mm2/s, P < 0.05), Tmax (ï¼»21.30 ± 10.78ï¼½ vs ï¼»50.22 ± 36.31ï¼½ s, P < 0.05), SImax (ï¼»1.75 ± 0.39ï¼½% vs ï¼»1.24 ± 0.41ï¼½%, P < 0.05), and Rmax (ï¼»20.20 ± 15.50ï¼½% vs ï¼»7.98 ± 6.25ï¼½%, P < 0.05). The expression of P504s was correlated negatively with the ADC value and Tmax (r = －0.60 and －0.37, P < 0.01) but positively with SImax and Rmax (r = 0.50 and 0.45, P < 0.01). CONCLUSIONS: 　The parameters of multi-modality MRI are correlated with the expression of P504s in PCa and can be used as imaging biomarkers for predicting the degrees of its malignancy.

Structure-activity relationships of rationally designed AMACR 1A inhibitors.

α-Methylacyl-CoA racemase (AMACR; P504S) is a promising novel drug target for prostate and other cancers. Assaying enzyme activity is difficult due to the reversibility of the 'racemisation' reaction and the difficulties in the separation of epimeric products; consequently few inhibitors have been described and no structure-activity relationship study has been performed. This paper describes the first structure-activity relationship study, in which a series of 23 known and potential rational AMACR inhibitors were evaluated. AMACR was potently inhibited (IC50 = 400-750 nM) by ibuprofenoyl-CoA and derivatives. Potency was positively correlated with inhibitor lipophilicity. AMACR was also inhibited by straight-chain and branched-chain acyl-CoA esters, with potency positively correlating with inhibitor lipophilicity. 2-Methyldecanoyl-CoAs were ca. 3-fold more potent inhibitors than decanoyl-CoA, demonstrating the importance of the 2-methyl group for effective inhibition. Elimination substrates and compounds with modified acyl-CoA cores were also investigated, and shown to be potent inhibitors. These results are the first to demonstrate structure-activity relationships of rational AMACR inhibitors and that potency can be predicted by acyl-CoA lipophilicity. The study also demonstrates the utility of the colorimetric assay for thorough inhibitor characterisation.

Expressions and Significance of Ki-67,p53 and P504s in Gastric Precancerous Lesions and Early Gastric Cancer / 胃肠病学

Background:The occurrence of gastric cancer is a gradual process with multiple factors and multiple steps. In addition to cytological and structural abnormalities,there are abnormal molecular expressions,which involve the activation of many oncogenes and the inactivation of tumor suppressor genes. Aims:To explore the expressions and significance of Ki-67,p53 and P504s in normal gastric mucosa,atrophic gastritis with intestinal metaplasia,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and early gastric cancer. Methods:A total of 44 cases of normal gastric mucosa,44 cases of atrophic gastritis with intestinal metaplasia,41 cases of low-grade intraepithelial neoplasia,38 cases of high-grade intraepithelial neoplasia and 35 cases of early gastric cancer from Jan. 2015 to Dec. 2016 at the Affiliated Drum Tower Hospital of Nanjing University Medical School were collected. Expressions of Ki-67,p53 and P504s were detected by immunohistochemical staining. Results:Compared with normal gastric mucosal tissue,the positivity rates of expression of Ki-67,p53 and P504s in atrophic gastritis with intestinal metaplasia,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and early gastric cancer were obviously increased (P＜0.05). With the increasing of severity of the lesion,the positivity rate gradually increased. Conclusions:The expressions of Ki-67,p53 and P504s are closely related to the occurrence and development of gastric cancer,and are involved in the early process of gastric cancer. The detections of these molecular markers are helpful for determining the severity and trend of the lesion,and beneficial for improving the detection rates of gastric precancerous lesion and early gastric cancer.

[The value of alpha-methylacyl-CoA racemase expression in the progression of colonic carcinoma]. / Valor de la expresión inmunohistoquímica de alfa-metilacil-CoA racemasa en la progresión del carcinoma de colon.

Alpha-methylacyl-CoA racemase (AMACR) expression has been demonstrated in several normal tissues and in diverse types of carcinoma. Our aim was to analyze the immunohistochemical expression of AMACR in the sequence-progression of colonic cancer. We studied 237 cases, including samples of normal mucosa of the colon, adenomas with different degrees of dysplasia, colonic carcinomas, lymph nodes and liver metastases of colonic carcinomas. A scale of intensity and percentage of expression was used to analyze the AMACR immunohistochemical profile. The expression was nearly absent in samples of normal mucosa, increased in both adenomas and carcinomas, decreased in lymph node metastases but was significantly increased in liver metastases.

Exploratory development of rapid immunohistochemical staining technique in prostate biopsy tissue frozen section diagnosis / 中国基层医药

in 30minutes.Antibody expression located accurately.Background stained clearly and no interfering signal.The back-ground was better than conventional immunohistochemistry of frozen remaining tissue.The positive expression rate of p40,34βE12,p504s with rapid immunohistochemistry in prostatic hyperplasia was 97.4%(77 /79),93.7%(74 /79),0%(0 /79),and in prostatic carcinoma was 0%(0 /39),0%(0 /39),97.4%(38 /39).The positive expression rate of p40,34βE12,p504s with conventional immunohistochemistry in prostatic hyperplasia was 96.2%(76 /79), 93.7%(74 /79),2.5%(2 /79),and in prostatic carcinoma was 0%(0 /39),0%(0 /39),92.3%(36 /39).The difference of expression between prostatic hyperplasia and prostatic carcinoma with rapid immunohistochemical detec-tion p40 group:χ2 =109.402,P =0.000,34βE12 group:χ2 =97.971,P =0.000,p504s group:χ2 =113.537,P =0.000;The difference of expression between prostatic hyperplasia and prostatic carcinoma with conventional immuno-histochemical detection p40 group:χ2 =105.410,P =0.000,34βE12 group:χ2 =97.971,P =0.000,p504s group:χ2 =96.388,P =0.000;The expression of prostatic hyperplasia with between rapid immunohistochemical detection and conventional immunohistochemical detection 34βE12 group was identical,p40 group:χ2 =0.207,P =0.649, p504s group:χ2 =2.026,P =0.155;The expression of conventional immunohistochemical detection with between rap-id immunohistochemical detection and conventional immunohisto -chemical detection p40 group and 34βE12 group were identical,p504s group:χ2 =1.054,P =0.305.The expression of three markers between prostatic hyperplasia and prostatic carcinoma had statistical significance(P 0.05).Conclusion MaxVision rapid immunohisto -chemical staining technique has the advantages of rapid,accurate,timely.It could be used to rapid diagnosis of prostate biopsy tissue.The combined detection of p40,34βE12,p504s has very high practi-cal value in the differential diagnosis of benign and malignant lesions of the prostate.

A cross sectional study of p504s, CD133, and Twist expression in the esophageal metaplasia dysplasia adenocarcinoma sequence.

The incidence of esophageal adenocarcinoma has increased dramatically over recent years and Barrett's esophagus is considered the most established risk factor for its development. Endoscopic surveillance of Barrett's esophagus is therefore recommended but hinges on histological interpretation of randomly taken biopsies which is poorly reproducible. The use of biomarkers presents an opportunity to improve our ability to risk-stratify these patients.We examined three biomarkers namely p504s, CD133, and Twist in the setting of Barrett's esophagus, low-grade dysplasia, and esophageal adenocarcinoma to evaluate differential expression between benign, dysplastic, and malignant Barrett's tissue in an exploratory cross-sectional study. Twenty-five cases each of Barrett's esophagus, low-grade dysplasia, and esophageal adenocarcinoma were included along-with 25 cases of esophagectomy resections for Barrett's adenocarcinoma. The biomarkers were immunostained on automated Ventana(®) immunostainer. The biopsies were assessed for biomarker expression by two independent observers. Granular cytoplasmic staining of p504s was observed in dysplastic Barrett's biopsies and esophageal adenocarcinoma but not in Barrett's esophagus. Apical and membranous CD133 expression was also observed in dysplastic Barrett's and esophageal adenocarcinoma. Nuclear Twist expression was seen predominantly in stromal cells. There was increased p504s expression in dysplastic Barrett's esophagus and esophageal adenocarcinoma compared with controls. CD133 expression was detected for the first time in esophageal adenocarcinoma and dysplastic Barrett's esophagus. Twist expression was not convincing enough to be labeled as Barrett's biomarker. p504s and CD133 have the potential to differentiate benign from malignant Barrett's tissue in this exploratory study. Their validity should be established in prospective longitudinal studies.

Paneth cell-like change in benign prostate can account for P504S (AMACR) reactivity.

Paneth cell-like neuroendocrine metaplasia of benign and cancerous prostate was described in 1992. Here, we note that P504S (AMACR), the cytoplasmic marker for prostate cancer used alone or in concert with basal cell markers, can be strongly reactive in benign prostatic acini with Paneth cell-like change.

Basal cell hyperplasia (BCH) versus high grade prostatic intraepithelial neoplasia (HGPIN) in tiny prostatic needle biopsies: Unusual diagnostic dilemma.

BACKGROUND: Histopathological differentiation between BCH and HGPIN in prostatic needle biopsies is a diagnostic challenge. The gold standard for detection of HGPIN and BCH is histopathological examination; however subjectivity in interpretation and tiny volume of obtained tissue hamper reliable diagnosis. AIMS: The aim of this study was to assess usefulness of using the p63 and p504s to solve this problem. Although the use of p63 and p504s is now well established in differentiation between preneoplastic and neoplastic prostatic lesions, their usefulness in tiny tissue material is, however, not fully studied. METHODS: The study included a spectrum of 30 prostatic needle biopsies (5 BCH, 10 HGPIN, 10 indefinite luminal proliferations where BCH and HGPIN could not be distinguished from each other and 5 adenocarcinomas). H&E stained sections were examined for histopathological features. Other sections were stained immunohistochemically with p63 and p504s. RESULTS: The mean age of patients was 69 (SD=7.6) years. PSA range was 1.3-2.7 ng/ml. Ultrasongraphic findings were unremarkable. All BCH showed p504s-/p63+ pattern, All HGPIN had p504s+/p63+ pattern while carcinomas were p504s+/p63-. After immunostaining combined with histopathological features; the 10 indefinite specimens could be diagnosed as 4 BCH and 6 HGPIN. The article explains how applying this staining pattern on the challenging specimens, combined with histopathological features, can be helpful in proper identification of prostatic proliferations.

Different diagnostic value of p40 in benign and malignant lesions of the prostate / 肿瘤研究与临床

Objective To investigate the expression of p40 (ANp63),p504s and their diagnostic value in benign and malignant lesions of the prostate,also to compare with the expression of p63.Methods The expression of p40 (ANp63),p63 and p504s in 92 cases of benign prostatic hyperplasia and 67 cases of prostatic carcinoma were detected by immunohistochemical MaxVision method.Results p40 and p63 were positive in 95.7 ％ (88/92) and 87.0 ％ (80/92) of benign prostatic hyperplasia,and the intermittent and low expression in p63 were more common than those in p40.The positive expression rate of p40 was obviously higher than that of p63 in benign prostatic hyperplasia (x2 =4.381,P ＜ 0.05).Both p40 and p63 showed no expression in prostatic carcinoma,but p63 appeared with abnormal cytoplasmic staining in many cases of cancer cells,which was 17.9 ％ (12/67).The specificity of combined detection of p40 and p504s in the diagnosis of benign prostatic hyperplasia and prostate carcinoma was as high as 100 ％.Conclusion p40 is more sensitive than p63 in prostate basal cells.Combined detection of p40 and p504s is valuable to distinguish poorly differentiated benign prostatic hyperplasia from prostatic carcinoma.

Utility of α-methylacyl-coenzyme-A racemase (p504s) immunohistochemistry in distinguishing endometrial clear cell carcinomas from serous and endometrioid carcinomas.

The expression of α-methylacyl-coenzyme-A racemase (AMACR) has previously been reported in 75% to 100% of urethral/bladder clear cell carcinomas, tumors that are known to display broad phenotypic overlap with their identically named müllerian counterparts. Herein, we assess the utility of AMACR in distinguishing endometrial clear cell carcinomas (CCCs) from endometrial serous carcinomas (ESCs) and endometrial endometrioid carcinomas (EECs). A total of 111 endometrial carcinomas in a tissue microarray, including 49 CCCs, 13 ESCs, and 49 EECs, were assessed for AMACR immunoreactivity, with results scored semiquantitatively (scores 0, 1+, 2+, 3+ for 0%, 1%-5%, 6%-50%, >50% immunoreactive cells, respectively). Fifty (45%) of the 111 carcinomas were AMACR positive, with the following score distribution: CCC: 0 (n = 12), 1+ (n = 12), 2+ (n = 3), 3+ (n = 22); EEC: 0 (n = 38), 1+ (n = 4), 2+ (n = 4), 3+ (n = 3); ESC: 0 (n = 11), 1+ (n = 1), 2+ (n = 0), 3+ (n = 1). AMACR expression was significantly more frequent in CCC (75%) than in ESC (15%) or EEC (22%); P < .0001. The sensitivity and specificity of AMACR expression in classifying a carcinoma as CCC were 0.75 (95% confidence interval [CI], 0.61-0.86) and 0.79 (95% CI, 0.66-0.88), respectively, with an odds ratio of 11.62 (95% CI, 5-28; P < .001) and an area under the curve of 0.79 (95% CI, 0.68-0.88). These findings indicate that AMACR expression is strongly associated with CCC and displays a relatively robust diagnostic test performance. However, its practical utility may be limited by the focal nature of its expression in 32% of the AMACR-positive CCC cases as well as its expression in 15% to 22% of the non-CCC histotypes.