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Jonathan I Epstein - One of the best experts on this subject based on the ideXlab platform.

  • aberrant diffuse expression of p63 in adenocarcinoma of the prostate on needle biopsy and radical prostatectomy report of 21 cases
    The American Journal of Surgical Pathology, 2008
    Co-Authors: Adeboye O Osunkoya, Donna E Hansel, Xinlai Sun, George J Netto, Jonathan I Epstein
    Abstract:

    Aberrant diffuse expression of p63 in prostate carcinoma cells is a rare and poorly understood phenomenon. We studied 19 cases of prostate cancer with aberrant diffuse expression of p63 on needle biopsy and reviewed the subsequent radical prostatectomies in 6 cases. In 19/21 cases, 100% of the cancer nuclei stained intensely for p63, with 70% staining in the remaining 2 cases. Two additional radical prostatectomies with aberrant p63 staining with no needle biopsies available for review were also analyzed. On the hematoxylin and eosin-stained slides, 19/21 cases (90.5%) showed a distinctive morphology composed predominantly of glands, nests, and cords with atrophic cytoplasm, hyperchromatic nuclei, and visible nucleoli. Needle biopsy cases ranged from Gleason patterns 3 to 5 with tumor identified on one or more cores, ranging from a minute focus to 80% of the core. In all 8 radical prostatectomies p63 positive cancer was present, with in 2/8 cases both p63 positive cancer and usual p63 negative acinar prostate cancer. In all 8 cases, the tumors were organ confined with negative margins and there was no seminal vesicle involvement or lymph node metastasis. The presence of p63 positive atypical glands with an infiltrative pattern and perineural invasion on radical prostatectomy confirmed the needle biopsy diagnosis of carcinoma. Rarely, prostate cancer can aberrantly express diffuse p63 staining in a nonbasal cell distribution leading to the erroneous diagnosis of atrophy or atypical basal cell proliferation. The diagnosis of prostate cancer is based on the morphology and confirmed by the absence of high molecular weight cytokeratin staining and positivity for Alpha-Methylacyl-CoA Racemase in the atypical glands. Pathologists need to be aware of this rare and unusual phenomenon, which is a potential pitfall in prostate cancer diagnosis.

  • xanthoma of the prostate a mimicker of high grade prostate adenocarcinoma
    The American Journal of Surgical Pathology, 2007
    Co-Authors: Ai Ying Chuang, Jonathan I Epstein
    Abstract:

    Prostatic xanthoma may mimic high-grade prostatic adenocarcinoma or prostate cancer treated with hormone therapy. From 1995 to 2006, 40 cases of prostatic xanthoma were diagnosed at The Johns Hopkins Hospital. Thirty-four cases were received in consultation from outside institutions. Hematoxylin and eosin-stained or unstained slides were available in 27 cases (24 consultation cases; 3 in-house cases). Xanthoma was found on needle biopsy in 25 cases, with 2 cases noted on transurethral resection of prostate. Twenty-six cases contained only 1 focus of prostatic xanthoma with 1 case having 3 foci on the same core biopsy specimen. In 21 xanthomas, the lesions were small measuring 1 mm with the largest one measuring 2.5 mm. Xanthoma cells had small uniform, benign-appearing nuclei, small inconspicuous nucleoli, and abundant vacuolated foamy cytoplasm. No mitoses were identified. Focal necrosis was identified in 1 case. Most xanthomas were arranged in circumscribed solid nodular pattern (17 cases). Ten xanthomas consisted of cords and individual cells infiltrating the prostatic stroma, further mimicking high-grade prostate carcinoma. Two xanthomas contained a mixed circumscribed nodular pattern and infiltrating pattern. Of cases with the lesion still present on slides for immunohistochemistry, CD68 was diffusely strongly positive in 18/19 (94.7%) and CAM5.2 was positive in none of the cases 0/14 (0%). One of 15 (6.7%), 2/17 (11.8%), and 1/12 (8.3%) cases were positive for prostate-specific antigen, prostate-specific acid phosphatase, and Alpha-Methylacyl-CoA Racemase, respectively. Careful attention to morphology with adjunctive use of CD68 and CAM5.2 immunohistochemical stains are helpful in the diagnosis of prostatic xanthoma, especially in difficult cases with an infiltrative pattern.

  • how often does alpha methylacyl coa Racemase contribute to resolving an atypical diagnosis on prostate needle biopsy beyond that provided by basal cell markers
    The American Journal of Surgical Pathology, 2004
    Co-Authors: Ming Zhou, Hakan Aydin, Hillel Kanane, Jonathan I Epstein
    Abstract:

    BACKGROUND Alpha-Methylacyl-CoA-Racemase (AMACR), a recently discovered tumor marker for prostate cancer, is being used increasingly in conjunction with hematoxylin and eosin (HE of these 76 cases, 34 (44.7%) were changed to a final diagnosis of cancer. AMACR expression was positive, with moderate and strong staining in 30 of the 34 cases (88.2%), for which the immunohistochemical result converted the expert review atypical diagnosis to a final cancer diagnosis. Of these 34 cases, 11 underwent radical prostatectomy, and cancer was found in all cases. Three additional patients underwent repeat biopsy, and cancer was present in the repeat biopsy in 2 patients. The cases whose diagnosis was changed from "atypical" on expert review to cancer were all highly suspicious for cancer based on H&E histology and negative basal cell markers, yet a definitive cancer diagnosis could not be established because of small size, insufficient cytologic atypia, or biopsy artifact. CONCLUSION Interpretation and use of AMACR staining should be executed with caution. A negative AMACR stain can be seen in approximately 18% of cases considered to be cancer based on H&E stain combined with negative basal cell markers. A positive AMACR staining converted an atypical diagnosis, based on suspicious histology and negative basal cell marker stains, to cancer in approximately 10% (34 of 307) of cases thought to be atypical by contributing pathologists and in approximately 50% (34 of 76) of cases thought be atypical on expert review by a specialist in genitourinary pathology.

  • α methylacyl coa Racemase a variably sensitive immunohistochemical marker for the diagnosis of small prostate cancer foci on needle biopsy
    The American Journal of Surgical Pathology, 2003
    Co-Authors: Cristina Magigalluzzi, Jun Luo, Angelo M De Marzo, William B Isaacs, Jessica Hicks, Jonathan I Epstein
    Abstract:

    Expression of the Alpha-Methylacyl-CoA Racemase (AMACR) gene has recently been demonstrated by several groups to be markedly elevated in prostate cancer cells with little expression in benign prostate tissue and has been suggested as a molecular marker of prostate cancer on needle biopsy. There is scant data, however, as to the sensitivity and specificity of AMACR in the diagnosis of small foci of cancer on needle biopsy. A total of 209 needle biopsies of the prostate with small foci (<5% of a core) of prostatic adenocarcinoma were identified. A total of 175 cases were received in consultation by one of the authors (140 from a single institution and 35 from different outside institutions) and 34 cases were from our hospital file. Immunohistochemistry for high molecular weight cytokeratin and p63 was performed in all cases to confirm the diagnosis of cancer. Only AMACR staining that was significantly stronger than that of background benign glands was considered positive; 88% of all cases of prostate cancer were positive for AMACR. The sensitivity varied among the different groups: 100% for the in house cases, 87.1% for the cases from a single institution, and 80% for cases from different outside institutions. The mean percentage of stained glands in positive cases was 95.9%, with 150 (71.8%) cases showing 100% of the glands positive and 25 (12.0%) cases showing no staining. Because negative staining for basal cell markers, especially in a small focus of atypical glands, is not necessarily diagnostic of prostate cancer, positive staining for AMACR can increase the level of confidence in establishing a definitive malignant diagnosis. However, the sensitivity of AMACR staining may vary in specimens from different pathology laboratories, possibly related to differences in fixation and processing. It is important to optimize the staining technique for each laboratory and recognize that some small cancers on needle biopsy may be AMACR negative.

  • expression and diagnostic utility of alpha methylacyl coa Racemase p504s in foamy gland and pseudohyperplastic prostate cancer
    The American Journal of Surgical Pathology, 2003
    Co-Authors: Ming Zhou, Zhong Jiang, Jonathan I Epstein
    Abstract:

    Foamy gland and pseudohyperplastic carcinomas are two uncommon variants of prostate cancer and often pose diagnostic challenges on needle biopsies. Alpha-Methylacyl-CoA-Racemase (AMACR) is a recently discovered tumor marker whose expression is significantly upregulated in prostate cancer. However, the original works only studied ordinary prostate cancer without reference to specific morphologic variants. Therefore, the expression and diagnostic utility of AMACR in specific variants of prostate cancer are unknown. In addition, two different antibodies, one monoclonal and one polyclonal, were used in the previous studies. The goal of this study is to examine the expression pattern and diagnostic utility of AMACR in foamy gland and pseudohyperplastic prostate cancer and to compare the diagnostic utility of the two anti-AMACR antibodies in the same prostate needle biopsy series. Prostate cancer with foamy gland or pseudohyperplastic features was retrieved from the Johns Hopkins Hospital Surgical Pathology file. Thirty needle biopsies harboring prostate cancer with foamy gland features and 17 needle biopsies harboring prostate cancer with pseudohyperplastic features were available for this study. Immunohistochemistry for AMACR was performed with two antibodies, a monoclonal one (P504S) and a polyclonal one (AMACR-p), using previously published protocols. Immunohistochemistry for high molecular weight cytokeratin and p63 was performed to confirm the cancer diagnosis. The AMACR staining intensity was graded as negative, weak, moderate, and strong. Only the staining that was significantly stronger than that of background benign glands was considered positive. A total of 68% and 62% of foamy gland prostate cancer was positive for AMACR with P504S and AMACR-p antibodies, respectively. A total of 77% and 70% of pseudohyperplastic prostate cancer was positive for AMACR with P504S and AMACR-p antibodies, respectively. Staining was often heterogeneous with different staining intensities within the same lesion. The mean percentage of stained glands in positive cases was 74.4% (range 25-100%) with P504S and 78.9% (range 20-100%) with AMACR-p in foamy gland prostate cancer and 91% (range 10-100%) with P504S, and 86.7% (range 10-100%) with AMACR-p in pseudohyperplastic prostate cancer. Seven foci of high-grade prostatic intraepithelial neoplasia present in the study cases were all positive for AMACR. The two antibodies were not statistically different in their sensitivity and specificity. In conclusion, AMACR is potentially a useful diagnostic marker for foamy gland and pseudohyperplastic prostate cancer in the following setting. When the pathologist favors the diagnosis of these variants of cancer on routine stained sections and stains for basal cells are negative, yet still a definitive diagnosis of cancer is difficult because of the cancers' deceptively benign appearance, positive staining for AMACR can provide the additional confidence to establish a definitive malignant diagnosis. The major caveat in the interpretation of positive staining is that high-grade prostatic intraepithelial neoplasia cannot be in the differential diagnosis.

Ximing J Yang - One of the best experts on this subject based on the ideXlab platform.

  • preparation and characterization of the antibody recognizing amacr inside its catalytic center
    International Journal of Oncology, 2017
    Co-Authors: B V Popov, Gleb I Sutula, N S Petrov, Ximing J Yang
    Abstract:

    Alpha-Methylacyl-CoA Racemase (AMACR) catalyzes the β-oxidation of fatty acids and is overexpressed in carcinomas in various organs, while its inactivation results in the inhibition of cancer growth. In the present study, we prepared and characterized 20 different mouse monoclonal antibodies against human AMACR. In the course of biopanning of a phage peptide commercial library against in-house prepared 6H9 and 2A5, and commercial 13H4 antibodies, 10 phage mimotopes recognized by each type of the antibody were selected. Using the program Pepitope and the crystal structure of AMACR from Mycobacterium tuberculosis, we reveal for the first time, at least to the best of our knowledge, that the epitopes recognizing the antibody against AMACR are composed of conformation sequences localized inside the AMACR catalytic center. When delivered into live HeLa cells using cationic lipid-based PULSin reagent, the specific antibodies against AMACR were co-localized with peroxisomes. The in-house made 6H9 antibody exhibited a low level of this co-localization compared to the commercially available 63340 antibody, and did not inhibit the growth rate of HeLa and T98G cells. The results obtained suggest that antibody against AMACR may possess anti-AMACR catalytic activity and needs to be further investigated as a potential drug for use in anticancer therapy. On the whole, in this study, we generated several clones of AMACR antibodies and demonstrated that these antibodies can be colonized into live cells. Currently, we are testing the growth inhibitory properties of these antibodies against AMACR.

  • alpha methylacyl coa Racemase amacr expression in normal prostatic glands and high grade prostatic intraepithelial neoplasia hgpin association with diagnosis of prostate cancer
    The Prostate, 2005
    Co-Authors: Vijayalakshmi Ananthanarayanan, Ximing J Yang, Ryan Deaton, Michael R Pins, Peter H Gann
    Abstract:

    BACKGROUND Alpha-Methylacyl-CoA Racemase (AMACR) is strongly expressed in prostate cancer with variable expression in high-grade prostatic intraepithelial neoplasia (HGPIN) and low expression in normal prostate. We examined whether AMACR expression in HGPIN and normal tissue was associated with subsequent diagnosis of cancer or proximity to a cancer focus. METHODS Needle core biopsies from 45 patients with isolated HGPIN, 12 radical prostatectomy (RP) specimens with prostatic carcinoma and 6 cystoprostatectomies without prostatic carcinoma were immunostained for AMACR. Among patients with HGPIN, 23 (cases) showed cancer on a later biopsy and 22 (controls) had no cancer with at least 3 consecutive negative biopsies. RESULTS In the biopsy set, the mean AMACR expression per gland in the normal compartment of the cases (0.29) was significantly higher than the controls (0.21) (P = 0.0006). In the RP set, normal glands near a cancer focus had higher mean AMACR expression than those that were distant (P = 0.0006). There was no difference within the HGPIN compartment between cases and controls in the biopsies, or between near and distant glands in the RP set. Mean AMACR staining of normal glands in the cystoprostatectomy specimens was significantly lower than in normal glands in close proximity to a cancer focus. CONCLUSIONS Higher expression of AMACR in normal glands near a focus of cancer, as well as in the subjects eventually showing cancer, suggests a possible field effect in prostatic carcinogenesis. AMACR expression in normal glands therefore might be a useful predictor for repeat biopsy outcomes or as an intermediate endpoint in chemoprevention studies. © 2004 Wiley-Liss, Inc.

  • expression of alpha methylacyl coa Racemase in papillary renal cell carcinoma
    The American Journal of Surgical Pathology, 2004
    Co-Authors: Maria Tretiakova, Ximing J Yang, Sunati Sahoo, Masayuki Takahashi, Muge Turkyilmaz, Nicholas J Vogelzang, Fan Lin, Thomas Krausz, Bin Tean Teh
    Abstract:

    Alpha-Methylacyl-CoA Racemase (AMACR) was first discovered by using cDNA microarray technology as a molecular marker for prostate cancer. Our recent microarray analysis of renal cell carcinomas showed a significant increase of AMACR mRNA levels in papillary renal cell carcinomas, but not in other subtypes. To investigate the value of this marker in pathologic diagnosis, we analyzed AMACR mRNA levels in cDNA microarrays from 70 kidney tumors. Furthermore, we evaluated the AMACR expression in 165 kidney tumors on tissue microarrays and 51 papillary carcinomas of other organs by immunohistochemistry. AMACR mRNA was significantly overexpressed in 7 of 8 papillary renal cell carcinomas with an average of 5.2-fold increase, and only in 2 of 62 nonpapillary kidney tumors. Immunohistochemistry demonstrated strong AMACR positivity in all cases of papillary renal cell carcinomas (41 of 41, 100%), including 6 metastatic papillary renal cell carcinomas, but only focal or weak reactivity in the minority (18 of 124, 15%) of other renal tumors including 13 of 52 clear cell renal cell carcinomas, 3 of 20 oncocytomas, and 2 of 17 urothelial carcinomas. All chromophobe (0 of 18) and sarcomatoid components of renal cell carcinomas (0 of 15) were negative for AMACR. Weak or focal AMACR immunoreactivity was detected in only 4 of 51 (8%) papillary carcinomas arising in other organs (2 of 14 thyroid, 2 of 13 lung, 0 of 6 breast, 0 of 6 endometrium, 0 of 6 ovary, and 0 of 6 pancreas). Using a combination of cDNA microarrays, tissue microarrays, and immunohistochemistry, we identified AMACR as a marker for papillary renal cell carcinoma, which could be valuable in subclassification of renal cell carcinomas and in the differential diagnosis of a metastatic papillary carcinoma.

  • p504s α methylacyl coa Racemase a useful marker for diagnosis of small foci of prostatic carcinoma on needle biopsy
    The American Journal of Surgical Pathology, 2002
    Co-Authors: Zhong Jiang, Gary R Fanger, Karen Dresser, Bruce A. Woda, Ximing J Yang
    Abstract:

    Establishing a definitive diagnosis of malignancy in prostate needle biopsies with very small foci of adenocarcinoma is a major diagnostic challenge for surgical pathologists. A positive diagnostic marker specific for prostatic adenocarcinoma may enhance our ability to detect limited prostate cancer and reduce errors in diagnosis. P504S, also known as Alpha-Methylacyl-CoA Racemase, recently identified by cDNA subtraction and microarray technology, might serve as such a specific marker because it has been demonstrated to be highly expressed in prostatic adenocarcinoma, but not in benign prostatic glands. However, whether small foci of carcinoma can be reliably detected by this marker is a crucial question for its clinical application. The aim of this study was to assess the utility of P504S immunohistochemistry in detecting small amounts of prostate cancer in prostate needle biopsies. A total of 142 prostate needle biopsies, including 73 cases with a small focus of prostatic adenocarcinoma (staining confirmed the absence of basal cells in the focus of carcinoma in all 73 cases. The high specificity and sensitivity of P504S in the detection of minimal prostatic adenocarcinoma indicated its potential diagnostic value in clinical practice. Using a combination of P504S and 34betaE12 can help the diagnosis of limited prostatic adenocarcinoma on needle biopsy.

  • expression of α methylacyl coa Racemase p504s in atypical adenomatous hyperplasia of the prostate
    The American Journal of Surgical Pathology, 2002
    Co-Authors: Ximing J Yang, Chinlee Wu, Karen Dresser, Maria Tretiakova, Gary R Fanger, Bruce A. Woda, Zhong Jiang
    Abstract:

    : Atypical adenomatous hyperplasia (AAH) of the prostate, also known as adenosis, is characterized by a proliferation of prostatic glands with abnormal architectural patterns, but without significant cytologic atypia. In some cases it may be difficult to distinguish AAH from prostatic carcinoma. Additionally, it is not clear whether AAH is a precursor lesion of prostatic adenocarcinoma. P504S, a protein highly expressed in prostatic adenocarcinoma, has been recently shown to be a marker of prostate cancer. The goal of this study is to examine the expression of P504S in AAH by immunohistochemistry. A total of 80 prostate specimens, including 40 cases of AAH (prostatectomy N = 30, biopsy N = 6, transurethral resection N = 4), 20 cases of prostatic adenocarcinomas, and 20 cases of benign prostatic hyperplasia, were studied. Immunohistochemistry for a prostate cancer marker Alpha-Methylacyl-CoA Racemase (P504S) and a basal cell-specific marker 34betaE12 was performed in all the cases. The 34betaE12 stain confirmed the presence of patchy basal cells in all 40 cases of AAH. P504S was undetectable in the majority of AAHs (33 of 40, 82.5%), focally expressed in four of 40 (10.0%), or diffusely positive only in three of 40 (7.5%) cases of AAH. Interestingly, two of seven P504S-positive AAHs were found adjacent to adenocarcinoma. In contrast, all benign prostatic hyperplasias (20 of 20, 100%) were negative for P504S, and all 20 cases of prostatic carcinomas (100%) showed a diffuse P504S staining pattern. These findings suggest that AAH is a heterogenous entity. The biologic significance of P504S expression in a small subset of AAH remains to be determined. Because most cases of AAH are negative for P504S, immunostaining of P504S is also of diagnostic value in distinguishing the majority of AAHs from prostatic adenocarcinoma.

Liang Cheng - One of the best experts on this subject based on the ideXlab platform.

  • distal tubular hyperplasia a proposal for a unique form of renal tubular proliferation distinct from papillary adenoma
    The American Journal of Surgical Pathology, 2021
    Co-Authors: Sean R Williamson, Khaleel I Alobaidy, Liang Cheng, Steven C Smith, Roni M Cox, Jesse K Mckenney, Neriman Gokden, Carrie L Phillips, Giovanna A Giannico, Alexander J Gallan
    Abstract:

    We identified an unusual pattern of renal tubular proliferation associated with chronic renal disease, found in 23 patients, diffusely (n=12), or focally (n=11). Incidence was 5% of end-stage renal disease kidneys from one institution (8/177) and 7/23 patients with acquired cystic kidney disease-associated renal cell carcinoma from another. Most (19 patients) had 1 or more neoplasms including papillary (n=9), acquired cystic kidney disease (n=8), clear cell (n=4), or clear cell papillary (n=3) renal cell carcinoma. All (20 men, 3 women) had end-stage renal disease. The predominant pattern (n=18) was the indentation of chronic inflammation into renal tubules forming small polypoid structures; however, 5 had predominantly hyperplastic epithelium with less conspicuous inflammation. In 14 patients both patterns were appreciable, whereas the remainder had only the inflammatory pattern. Immunohistochemistry was positive for cytokeratin 7, high-molecular-weight cytokeratin, PAX8, and GATA3. Staining for Alpha-Methylacyl-CoA Racemase was negative or weak, dramatically less intense than papillary neoplasms or proximal tubules. CD3 and CD20 showed a mixture of B and T lymphocytes in the inflammatory areas. Fluorescence in situ hybridization showed no trisomy 7 or 17 or loss of Y (n=9). We describe a previously uncharacterized form of renal tubular proliferation that differs from papillary adenoma (with weak or negative Alpha-Methylacyl-CoA Racemase, lack of trisomy 7 or 17, and sometimes diffuse distribution). On the basis of consistent staining for high-molecular-weight cytokeratin and GATA3, we propose the name distal tubular hyperplasia for this process. Future studies will be helpful to assess preneoplastic potential and etiology.

  • seminal vesicle intraepithelial neoplasia versus basal cell hyperplasia in a seminal vesicle
    European Urology, 2014
    Co-Authors: Rodolfo Montironi, Liang Cheng, Antonio Lopezbeltran, Andrea B Galosi, Francesco Montorsi, Marina Scarpelli
    Abstract:

    In the examination of >3000 radical prostatectomy specimens and their seminal vesicles (SVs), we came across a unique case of an intraepithelial abnormality in preexisting ducts and acini in the left SV of a 73-yr-old patient with prostatic adenocarcinoma. At low magnification, the epithelial lining was thicker than the surrounding normal ducts with obliteration of the acinar lumen. At high magnification, there were varying degrees of cell stratification. Prostate-specific antigen, prostate-specific acid phosphatase, prostate-specific membrane antigen, prostein (P501S), Alpha-Methylacyl-CoA Racemase, and GATA binding protein 3 (GATA3) were negative; p63, 34betaE12, cytokeratin 5/6, and p53 were positive in cells in basal and suprabasal positions, whereas CA-125 was expressed in the luminal cells. The case shows morphologic and immunohistochemical features similar to those of basal cell hyperplasia of the prostate and is different from the early neoplastic epithelial changes of the SV in the transgenic adenocarcinoma mouse prostate model (ie, SV intraepithelial neoplasia). To the best of our knowledge, there are no previous reports of such a change in a human SV. The clinical significance of this lesion is not known and is overshadowed by the presence of prostate cancer.

  • clear cell papillary renal cell carcinoma differential diagnosis and extended immunohistochemical profile
    Modern Pathology, 2013
    Co-Authors: Sean R Williamson, Liang Cheng, John N Eble, David J Grignon
    Abstract:

    Clear cell papillary renal cell carcinoma is a recently recognized renal neoplasm, composed of cells with clear cytoplasm lining cystic, tubular, and papillary structures. These tumors have immunohistochemical and genetic profiles distinct from clear cell renal cell carcinoma and papillary renal cell carcinoma. We studied morphologic and immunohistochemical features (cytokeratin 7 (CK7), carbonic anhydrase IX (CAIX), CD10, Alpha-Methylacyl-CoA Racemase, smooth muscle actin, desmin, estrogen and progesterone receptors) in 55 tumors from 34 patients, 8 of whom had end-stage renal disease. These tumors comprised 3% of all adult renal cell carcinoma resections over a period of 3 years. The patients’ ages ranged from 33 to 87 years (mean 61). Multiple tumors (2–8) were present in 9 patients. Other renal tumors were present concurrently in four patients and subsequently in two patients, including: oncocytoma, clear cell renal cell carcinoma, and multilocular cystic renal cell carcinoma. Sizes ranged from 0.2 to 7.5 (mean 2.0) cm; 87% were Fuhrman grade 2, and 96% were stage pT1a. Papillary architecture was usually limited to focal branching papillae (51% of 55 tumors) or small, blunt papillae (35%). Large areas of extensively branched papillae were present in only 14% of tumors. Almost all tumors (98%) included cysts, and 18 tumors were extensively (≥90%) cystic. Immunoprofile showed CK7+, AMACR−, CD10−, CAIX+ in the tubular and papillary components of all tumors; however, CD10 labeled the apical cell membrane of cyst epithelium in 59%. The stroma was focally actin positive (94%), with infrequent desmin expression (13%). Estrogen receptor and progesterone receptor were negative. During a median follow-up period of 56 months, no patient developed local recurrence, distant or lymph-node metastasis, or cancer death. Branched tubules, small papillae, and the immunohistochemical and molecular profiles aid in distinguishing these tumors from clear cell renal cell carcinoma and multilocular cystic renal cell carcinoma.

  • is atypical adenomatous hyperplasia of the prostate a precursor lesion
    The Prostate, 2011
    Co-Authors: Chen Zhang, Kenneth A Iczkowski, Rodolfo Montironi, Antonio Lopezbeltran, Gregory T Maclennan, Yan Li, Mingsheng Wang, Shaobo Zhang, Liang Cheng
    Abstract:

    BACKGROUND Alpha-Methylacyl-CoA Racemase (AMACR) is highly expressed in prostatic adenocarcinoma. The precursor nature of atypical adenomatous hyperplasia (AAH) is uncertain. METHODS One hundred twenty-one AAH foci from 101 patients who underwent transurethral prostatic resection or prostatectomy were immunohistochemically analyzed for AMACR, high molecular weight cytokeratin 34βE12, and p63 expression by a triple antibody (PIN4) cocktail stain. RESULTS Sixty-eight foci (56%) of AAH showed no AMACR immunostaining. Fourteen cases (12%) showed weak AMACR immunoreactivity in 1–9% of lesional cells. Sixteen cases (13%) showed strong immunopositivity for AMACR in >50% of lesional cells. AMACR expression in AAH was significantly higher in cases in which coexisting PCA was present, compared with its expression in AAH foci without coexisting PCA (P = 0.03). Strong diffuse AMACR positivity in over 50% of lesional cells was seen almost exclusively in AAH foci with coexisting PCA (P = 0.002). AMACR expression in AAH showed no correlation with patient age (P = 0.38), specimen type (P = 0.35), prostate weight (P = 0.80), zonal location (P = 0.50), distance to cancer (P = 0.28), Gleason score (P = 0.06), or pathologic stage (P = 0.23). Increased AMACR expression showed a negative correlation with the size of AAH foci (P = 0.03). All AAH lesions showed fragmented basal cell layers, highlighted by p63 and high molecular weight cytokeratin staining. CONCLUSIONS A significant percentage of AAH cases show stronger and more extensive AMACR expression when associated with prostatic adenocarcinoma, as compared to AAH foci found without coexisting prostate cancer. Our data provide additional evidence linking AAH to prostatic adenocarcinoma. Prostate 71:1746–1751, 2011. © 2011 Wiley Periodicals, Inc.

  • α methylacyl coa Racemase spliced variants and their expression in normal and malignant prostate tissues
    Urology, 2011
    Co-Authors: Bin Ouyang, Yuetkin Leung, Vinson Wang, Ethan Chung, Linda Levin, Bruce Bracken, Liang Cheng
    Abstract:

    The high mortality of prostate cancer (CaP) in men and the low specificity of the serum prostate-specific antigen (PSA) assay has generated great interest in finding new biomarkers that could specifically detect CaP at an earlier stage.1 P504S, or Alpha-Methylacyl-CoA Racemase (AMACR), was first discovered in 2000 as a specific marker for CaP.2 Jiang et al. soon validated the aberrant expression of AMACR transcripts in CaP and used the transcripts for detecting CaP antigen in needle biopsy specimens.3,4 Immunohistochemical staining with AMACR antibody alone or in combination with antibody to a basal cell marker is currently a standard adjuvant tool in CaP diagnosis, especially in needle biopsy specimens with ambiguous lesions.5–8 Overexpression of AMACR has also been reported in other human tumors, including those cancers originating from kidneys, liver, lymph nodes, and colon.9,10 AMACR catalyzes the conversion of phytanic and pristanic acid that is essential in the beta-oxidation of branched-chain fatty acids and bile acid intermediates.11 Six different variants of AMACR have been reported as IA, IAd, IIA, IIAs, IB, and IIB.12–14 These transcript variants are considered to be alternatively spliced from a single gene locus located in chromosome 5.15 These alternatively spliced variants of AMACR are grouped as type I and II according to the presence or absence, respectively, of intact exon 5 and are subclassified as A or B, on the basis of the existence or absence, respectively, of exon 3. IA, the most abundant variant, contains all five intact exons and codes for a protein of 382 amino acids. Overexpression of this enzyme may allow CaP cells to switch energy sources, thereby facilitating cancer progression. AMACR has been studied as a potential early cancer diagnostic biomarker through determining its protein level in western blot assays, its transcript level in urine with quantitative RT-PCR, and the DNA methylation status of promoter in cancer tissue and blood.16–18 We reported that a duplex assay of total AMACR (AMACRt) and prostate cancer antigen 3 (PCA3) transcripts from urine sediment could significantly increase the specificity of CaP detection.19 A small-scale study noted differential expression of A and B forms of AMACR transcripts in CaP tissue.13,14 Here, we report four novel AMACR alternatively spliced variants and evaluate the expression of AMACRt transcript and its ten individual variants in four prostate cell lines and 23 normal-cancer paired prostate tissues.

Zhong Jiang - One of the best experts on this subject based on the ideXlab platform.

  • expression and diagnostic utility of alpha methylacyl coa Racemase p504s in foamy gland and pseudohyperplastic prostate cancer
    The American Journal of Surgical Pathology, 2003
    Co-Authors: Ming Zhou, Zhong Jiang, Jonathan I Epstein
    Abstract:

    Foamy gland and pseudohyperplastic carcinomas are two uncommon variants of prostate cancer and often pose diagnostic challenges on needle biopsies. Alpha-Methylacyl-CoA-Racemase (AMACR) is a recently discovered tumor marker whose expression is significantly upregulated in prostate cancer. However, the original works only studied ordinary prostate cancer without reference to specific morphologic variants. Therefore, the expression and diagnostic utility of AMACR in specific variants of prostate cancer are unknown. In addition, two different antibodies, one monoclonal and one polyclonal, were used in the previous studies. The goal of this study is to examine the expression pattern and diagnostic utility of AMACR in foamy gland and pseudohyperplastic prostate cancer and to compare the diagnostic utility of the two anti-AMACR antibodies in the same prostate needle biopsy series. Prostate cancer with foamy gland or pseudohyperplastic features was retrieved from the Johns Hopkins Hospital Surgical Pathology file. Thirty needle biopsies harboring prostate cancer with foamy gland features and 17 needle biopsies harboring prostate cancer with pseudohyperplastic features were available for this study. Immunohistochemistry for AMACR was performed with two antibodies, a monoclonal one (P504S) and a polyclonal one (AMACR-p), using previously published protocols. Immunohistochemistry for high molecular weight cytokeratin and p63 was performed to confirm the cancer diagnosis. The AMACR staining intensity was graded as negative, weak, moderate, and strong. Only the staining that was significantly stronger than that of background benign glands was considered positive. A total of 68% and 62% of foamy gland prostate cancer was positive for AMACR with P504S and AMACR-p antibodies, respectively. A total of 77% and 70% of pseudohyperplastic prostate cancer was positive for AMACR with P504S and AMACR-p antibodies, respectively. Staining was often heterogeneous with different staining intensities within the same lesion. The mean percentage of stained glands in positive cases was 74.4% (range 25-100%) with P504S and 78.9% (range 20-100%) with AMACR-p in foamy gland prostate cancer and 91% (range 10-100%) with P504S, and 86.7% (range 10-100%) with AMACR-p in pseudohyperplastic prostate cancer. Seven foci of high-grade prostatic intraepithelial neoplasia present in the study cases were all positive for AMACR. The two antibodies were not statistically different in their sensitivity and specificity. In conclusion, AMACR is potentially a useful diagnostic marker for foamy gland and pseudohyperplastic prostate cancer in the following setting. When the pathologist favors the diagnosis of these variants of cancer on routine stained sections and stains for basal cells are negative, yet still a definitive diagnosis of cancer is difficult because of the cancers' deceptively benign appearance, positive staining for AMACR can provide the additional confidence to establish a definitive malignant diagnosis. The major caveat in the interpretation of positive staining is that high-grade prostatic intraepithelial neoplasia cannot be in the differential diagnosis.

  • p504s α methylacyl coa Racemase a useful marker for diagnosis of small foci of prostatic carcinoma on needle biopsy
    The American Journal of Surgical Pathology, 2002
    Co-Authors: Zhong Jiang, Gary R Fanger, Karen Dresser, Bruce A. Woda, Ximing J Yang
    Abstract:

    Establishing a definitive diagnosis of malignancy in prostate needle biopsies with very small foci of adenocarcinoma is a major diagnostic challenge for surgical pathologists. A positive diagnostic marker specific for prostatic adenocarcinoma may enhance our ability to detect limited prostate cancer and reduce errors in diagnosis. P504S, also known as Alpha-Methylacyl-CoA Racemase, recently identified by cDNA subtraction and microarray technology, might serve as such a specific marker because it has been demonstrated to be highly expressed in prostatic adenocarcinoma, but not in benign prostatic glands. However, whether small foci of carcinoma can be reliably detected by this marker is a crucial question for its clinical application. The aim of this study was to assess the utility of P504S immunohistochemistry in detecting small amounts of prostate cancer in prostate needle biopsies. A total of 142 prostate needle biopsies, including 73 cases with a small focus of prostatic adenocarcinoma (staining confirmed the absence of basal cells in the focus of carcinoma in all 73 cases. The high specificity and sensitivity of P504S in the detection of minimal prostatic adenocarcinoma indicated its potential diagnostic value in clinical practice. Using a combination of P504S and 34betaE12 can help the diagnosis of limited prostatic adenocarcinoma on needle biopsy.

  • expression of α methylacyl coa Racemase p504s in atypical adenomatous hyperplasia of the prostate
    The American Journal of Surgical Pathology, 2002
    Co-Authors: Ximing J Yang, Chinlee Wu, Karen Dresser, Maria Tretiakova, Gary R Fanger, Bruce A. Woda, Zhong Jiang
    Abstract:

    : Atypical adenomatous hyperplasia (AAH) of the prostate, also known as adenosis, is characterized by a proliferation of prostatic glands with abnormal architectural patterns, but without significant cytologic atypia. In some cases it may be difficult to distinguish AAH from prostatic carcinoma. Additionally, it is not clear whether AAH is a precursor lesion of prostatic adenocarcinoma. P504S, a protein highly expressed in prostatic adenocarcinoma, has been recently shown to be a marker of prostate cancer. The goal of this study is to examine the expression of P504S in AAH by immunohistochemistry. A total of 80 prostate specimens, including 40 cases of AAH (prostatectomy N = 30, biopsy N = 6, transurethral resection N = 4), 20 cases of prostatic adenocarcinomas, and 20 cases of benign prostatic hyperplasia, were studied. Immunohistochemistry for a prostate cancer marker Alpha-Methylacyl-CoA Racemase (P504S) and a basal cell-specific marker 34betaE12 was performed in all the cases. The 34betaE12 stain confirmed the presence of patchy basal cells in all 40 cases of AAH. P504S was undetectable in the majority of AAHs (33 of 40, 82.5%), focally expressed in four of 40 (10.0%), or diffusely positive only in three of 40 (7.5%) cases of AAH. Interestingly, two of seven P504S-positive AAHs were found adjacent to adenocarcinoma. In contrast, all benign prostatic hyperplasias (20 of 20, 100%) were negative for P504S, and all 20 cases of prostatic carcinomas (100%) showed a diffuse P504S staining pattern. These findings suggest that AAH is a heterogenous entity. The biologic significance of P504S expression in a small subset of AAH remains to be determined. Because most cases of AAH are negative for P504S, immunostaining of P504S is also of diagnostic value in distinguishing the majority of AAHs from prostatic adenocarcinoma.

Alessandra Viglio - One of the best experts on this subject based on the ideXlab platform.

  • small bowel adenocarcinomas featuring special at rich sequence binding protein 2 satb2 expression and a colorectal cancer like immunophenotype a potential diagnostic pitfall
    Cancers, 2020
    Co-Authors: Giuseppe Neri, Giovanni Arpa, Camilla Guerini, Federica Grillo, Marco Vincenzo Lenti, Paolo Giuffrida, Daniela Furlan, Fausto Sessa, Erica Quaquarini, Alessandra Viglio
    Abstract:

    Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn’s disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and Alpha-Methylacyl-CoA Racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7−/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7−/CK20- SBAs were enriched with MMR-deficient cases (71%) and patients with CK7−/CK20− or CK7−/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20− or CK7+/CK20+ cancers (p = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7−/CK20− cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup.

  • Small bowel adenocarcinomas featuring special at-rich sequence-binding protein 2 (Satb2) expression and a colorectal cancer-like immunophenotype: A potential diagnostic pitfall
    'MDPI AG', 2020
    Co-Authors: Giuseppe Neri, Giovanni Arpa, Camilla Guerini, Federica Grillo, Marco Vincenzo Lenti, Paolo Giuffrida, Daniela Furlan, Fausto Sessa, Erica Quaquarini, Alessandra Viglio
    Abstract:

    Simple Summary Since small bowel adenocarcinoma may mimic a colorectal primary neoplasm histologically, it is pivotal to find biomarkers to discriminate these two biologically distinct neoplasms. The aim of our study was to evaluate the expression of special AT-rich sequence-binding protein 2 (SATB2), expressed in the vast majority of colorectal carcinomas, and other gastrointestinal phenotypic markers, such as cytokeratin 7, cytokeratin 20 and caudal type homeobox 2 (CDX2), in 100 small bowel adenocarcinomas. We identified 20 SATB2-positive small bowel adenocarcinomas, including nine sporadic cancers, seven celiac disease-associated cancers and four Crohn's disease-associated small bowel adenocarcinomas. Six small bowel adenocarcinomas, including two cases associated with celiac disease and four sporadic, displayed a full colorectal carcinoma-like immunoprofile. Unlike SATB2, cytokeratin patterns stratified small bowel adenocarcinoma patient prognosis. The small bowel should be considered as one of the possible sites of origin in cancers of unknown primary, even when the neoplasm shows a colorectal carcinoma-like immunoprofile. Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn's disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and Alpha-Methylacyl-CoA Racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7-/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7-/CK20- SBAs were enriched with MMR-deficient cases (71%) and patients with CK7-/CK20- or CK7-/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20- or CK7+/CK20+ cancers (p = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7-/CK20- cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup