Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007112 (prostatic adenocarcinoma)
 2,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diazepam-binding inhibitor (DBI)/acyl-CoA-binding protein (ACBP) is a highly conserved 10-kD polypeptide expressed in various organs and implicated in the regulation of multiple biological processes such as GABAA/benzodiazepine receptor modulation, acyl-CoA metabolism, steroidogenesis, and insulin secretion. To extend our knowledge about the biology of DBI/ACBP and to elucidate the molecular mechanisms responsible for regulating DBI/ACBP gene expression, we have studied the androgen-regulated expression of DBI/ACBP transcripts in the human prostatic adenocarcinoma cell line LNCaP and have cloned and characterized a human gene encoding DBI/ACBP. Northern blotting, reverse transcription-assisted polymerase chain reaction (RT-PCR), ribonuclease protection, and 5' RACE analysis (rapid amplification of cDNA ends) of DBI/ACBP transcripts in LNCaP cells revealed androgen-regulated expression of multiple transcripts originating from multiple transcription start sites and alternative processing. The most abundant type of transcripts (referred to as type 1 transcripts) encodes genuine DBI/ACBP of 86 amino acids, while the minor type (type 2 transcripts) harbors an insertion of 86 bases and might encode an unrelated protein of 67 amino acids. Examination of a cloned DBI/ACBP gene revealed a structural organization of four exons present in all transcripts and one alternatively used exon present only in type 2 transcripts. The promoter region is located in a CpG island and lacks a canonical TATA box. Transient transfection of DBI/ACBP promoter fragments into LNCaP cells demonstrated that a region of 1.1 kb upstream of the translation start site is able to drive high-level expression of luciferase in LNCaP cells in an androgen-regulated fashion. Taken together these data indicate that the isolated human gene encoding DBI/ACBP is functional, has a high degree of structural similarity with the corresponding rat gene, exhibits hallmarks of a typical housekeeping gene, and harbors cis-acting elements that are at least partially responsible for androgen-regulated transcription in LNCaP cells.
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PMID:A human gene encoding diazepam-binding inhibitor/acy1-CoA-binding protein: transcription and hormonal regulation in the androgen-sensitive human prostatic adenocarcinoma cell line LNCaP. 863 49

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.
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PMID:Alpha-methylacyl CoA racemase (P504S): overview and potential uses in diagnostic pathology as applied to prostate needle biopsies. 1464 45

Alpha-Methylacyl-CoA racemase (AMACR, P504S) has recently been shown to be a useful marker for the diagnosis of prostatic adenocarcinoma and a potential aid in its distinction from its many mimics, one of which is the benign lesion, nephrogenic adenoma (NA). The goal of this study was to assess the expression of AMACR in NA by immunohistochemistry, as well as other potentially useful markers, high-molecular-weight cytokeratin clone 34betaE12, p63, and prostate-specific antigen (PSA). AMACR was expressed in 4/4 NAs involving the prostatic urethra and underlying stroma, and in 3/16 NAs involving the bladder. The prostatic cases showed circumferential granular cytoplasmic AMACR expression of at least moderate intensity, in >75% of tubules in 3 cases and in <10% of tubules in the remaining case. The AMACR-positive cases in the bladder typically showed focal weak noncircumferential staining of the tubules and stronger staining of the cells lining the papillae. 34betaE12 staining was observed in 1/4 prostatic NAs and 4/16 bladder NAs, typically in a cytoplasmic pattern in a minority of cells. p63 and PSA were negative in all cases. Our data indicate that NA of the prostatic urethra commonly expresses AMACR and lacks basal cell-specific markers, making it not only a potential morphologic mimic of prostatic adenocarcinoma but also a significant immunohistochemical mimic as well. Awareness of NA as a significant pitfall in the diagnosis of prostatic adenocarcinoma and careful examination of hematoxylin and eosin-stained sections remains the key to the correct diagnosis, which can be supported by a negative PSA stain.
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PMID:Expression of alpha-methylacyl-CoA racemase (P504S) in nephrogenic adenoma: a significant immunohistochemical pitfall compounding the differential diagnosis with prostatic adenocarcinoma. 1609 17

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.
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PMID:Immunohistochemical detection of P504S in primary and metastatic renal cell carcinomas. 1535 42

Alpha-methyl CoA racemase (AMACR) is overexpressed in several human cancers, most notably colon and prostate. AMACR expression in the prostate has been investigated primarily in patients, in an older age group, treated for prostatic carcinoma and benign prostatic hypertrophy. No studies have assessed the age distribution of AMACR expression in normal men. Archival paraffin-embedded prostate tissue from 41 organ donor men (age range, 13-63 years) with no evidence of prostate neoplasia was stained with a monoclonal antibody for AMACR. Intensity was graded on a scale of 0 to 3. Semi-quantitative analysis of staining in acinar cells was used to generate a composite score (CS) [Sigma(% area x intensity)] for each case. Nondonor cases with foci of prostate cancer and high-grade prostatic intraepithelial neoplasia (PIN) were used as external positive controls for AMACR. These sections were also stained for Ki-67, to assess proliferative index. The 41 cases encompassed different age groups (13-20 years, N = 11; 20-45 years, N = 17; >45 years, N = 13). Acinar cells showed granular cytoplasmic staining. Focal positive staining was also seen in the prostatic urethra and the periurethral glands. There was wide variation in the level of expression within each age group. The level of expression seen in subjects younger than 45 years was higher (mean CS = 41.3; median CS = 22.5) than that seen in subjects older than 45 years (mean CS = 8.8; median CS = 9.0) with a P value of 0.01. Most cases in the control set of prostatic adenocarcinoma cases showed moderate to strong staining. A negative correlation was seen evaluating CS and age in subjects 20 years of age and older (r = -0.47). Ki-67 staining was variable. 1) AMACR expression can be seen in benign prostatic glandular epithelium, across all age groups. However, it is age-related, with significantly lower expression in subjects younger than 45 years. This could account for the negative staining reported in benign glands, due to biased sampling of the older population. 2) Focal positive staining is seen in the prostatic urethra and periurethral glands in 71% of the cases, with no age correlation. This is of concern because this epithelium could potentially be misinterpreted as foci of PIN. 3) The low expression of AMACR in benign glands in the older age group makes this marker useful in detecting malignancy. However, AMACR staining should be interpreted with caution and the diagnosis of PIN or prostate cancer should be rendered only with convincing histologic evidence. 4) Ki-67 staining was very variable and showed no correlation with age and AMACR expression levels. AMACR expression had no correlation with proliferative index.
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PMID:Age-associated changes in alpha-methyl CoA racemase (AMACR) expression in nonneoplastic prostatic tissues. 1622 9

Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.
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PMID:Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer. 1672 45

Although the diagnosis of usual prostatic adenocarcinoma is not difficult by itself, problems may occur with diagnosis of small carcinomas in punch biopsies. Often small groups of suspicious glands are found with indistinct basal cell layer and lack of immunohistochemical expression of cytokeratin clone 34betaE12 or p63. Despite disturbed architecture, carcinoma cannot be diagnosed without cytological criteria of malignancy, especially prominent nucleoli. This is not only a frequent problem in routine diagnostic slides but also in consultation cases. The consequence of the diagnosis "suspicious" is repeat biopsy after an interval of 6-12 months. Recently, a new marker for prostatic carcinoma an alpha methyl CoA-racemase (P504S) has been tested. P504S is overexpressed in carcinoma-cells of the prostate. Together with negative basal cell marker P63 and positive reaction of P 504S this imunohistochemical combination confirms the diagnosis in 35-45% of so called suspicious prostate biopsies. Facit: this group of patients have now a distinct diagnosis and must have a definite treatment without repeat biopsy.
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PMID:[Prostatic adenocarcinoma--still a diagnostic problem]. 1689 46

Foamy gland carcinoma is a variant of adenocarcinoma of the prostate that typically is assigned a Gleason score 3+3=6. The morphologic features of high foamy gland carcinoma have not been previously studied. We analyzed 55 cases of high-grade (Gleason score 7 or greater) foamy gland carcinoma of the prostate in needle biopsy (n=49) or transurethral resection (n=6) specimens. The number of cores involved by high-grade foamy gland carcinoma ranged from 1 to 12, with more than 1 core involved in 61% of cases (mean 3.4 cores). On average, 84% of the total tumor volume was foamy gland carcinoma, with high-grade foamy gland cancer averaging 73% of the total foamy gland carcinoma. The following results pertain only to the high-grade foamy gland cancer component. The most common architectural pattern was cribriform (73%), followed by fused/poorly defined glands (55%), cords/single cells (11%), and solid sheets (5%). Nuclear enlargement was observed in 45 of the 55 studied cases (82%). Prominent nucleoli were either absent or infrequent in 38 cases (69%). Frequent to numerous prominent nucleoli were seen more frequently in foamy gland carcinoma with Gleason score 8 or above (52%) than those with Gleason score 7 (16%) (P<0.004). Mitotic figures were observed in 22 cases (40%), and present in 65% of the cases with Gleason score 8 or above, but only in 22% of the cases with Gleason score 7 (P<0.002). In 31 cases (56%), intraluminal dense pink secretions were identified. Perineural invasion and extraprostatic extension identified on the biopsy specimens were noted in 18 cases (33%) and in 5 cases (9%), respectively. In 18 cases (33%), there was at least a moderate stromal reaction. A moderate or greater stromal reaction was seen in 48% (11/23) of the cases with Gleason score 8 or above compared with 22% (7/32) of the cases with Gleason score 7 (P=0.04). In 6 cases, there was a peculiar extensive desmoplastic reaction almost obscuring the carcinoma component, 5 of which were Gleason scores 4+4=8. Concurrent ordinary acinar nonfoamy adenocarcinoma was encountered in 26 of 55 cases (47%) with the following Gleason scores: Gleason 6 (27%); Gleason 7 (27%); and Gleason 8 to 10 (46%). Associated ordinary high-grade prostatic intraepithelial neoplasia and foamy gland variant of high-grade prostatic intraepithelial neoplasia/intraductal adenocarcinoma were seen in 13 cases (24%) and 11 cases (20%), respectively. Of the 19 cases with available immunohistochemical stains for high molecular weight cytokeratin, 7 (37%) showed nonspecific labeling of cancer cells in a nonbasal cell pattern. A similar finding was seen in 1 of the 7 (14%) cases with available stains for p63. Alpha-methyl-CoA racemase positivity was noted in all 9 cases stained. In summary, uncommonly foamy gland carcinoma consists of cribriform, fused/poorly formed glands, cords/single cells, and solid sheets typical of Gleason patterns 4 and 5. High-grade foamy gland cancer shares certain morphologic features with more typical lower-grade foamy gland cancer including relatively bland nuclei with more difficult to identify nucleoli and frequent intraluminal dense pink secretions. However, consistent with their higher architectural grade, high-grade foamy gland cancers had more prominent nucleoli and increased mitotic figures compared with lower-grade foamy gland cancer. A unique subset of high-grade foamy gland carcinoma poses particularly difficult diagnostic challenges, with scattered, scant, relatively bland foamy glands imbedded in an extensive densely sclerotic desmoplastic stroma.
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PMID:High-grade foamy gland prostatic adenocarcinoma on biopsy or transurethral resection: a morphologic study of 55 cases. 1903 62

Prostate adenocarcinoma can manifest as a fairly indolent tumor or as a very aggressive cancer with significant invasive and metastatic potential. Common metastatic sites include bone, liver, lymph nodes, and adrenal glands. Dermatologic manifestations are rare. We present a case of a man who presented with breast skin changes that mimicked inflammatory breast carcinoma with specialized testing ultimately giving a diagnosis of metastatic prostatic adenocarcinoma. A 78-year-old man presented with left breast redness and swelling. Examination revealed an erythematous rash with subcutaneous edema over the left hemithoracic area. A breast ultrasound showed no focal mass, and a breast core biopsy had no evidence of tumor. A skin biopsy showed metastatic carcinoma in dermal lymphatics, and the tumor was found to have no estrogen or progesterone receptors or HER2 expression. Computed tomography scans, positron emission tomography, and a nuclear bone scan revealed widespread skeletal metastases. The patient received a 3-month course of capecitabine and cyclophosphamide with no improvement in his skin lesions. Subsequent immunohistochemical staining on the tumor specimen was positive for prostate-specific antigen (PSA) and alpha-methyl-CoA-racemase, confirming a diagnosis of metastatic prostatic adenocarcinoma. He received leuprolide and bicalutamide and demonstrated significant improvement with near-complete resolution of his skin lesions and a decrease in his PSA level. Prostatic adenocarcinoma presenting initially as a breast malignancy is a rarely recognizable clinical event. Undoubtedly, increased awareness and recognition of the rare entity described herein will allow for the prompt initiation of specific therapies, which might be of benefit to many patients.
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PMID:Metastatic prostatic adenocarcinoma mimicking inflammatory breast carcinoma: a case report. 2013 50

Cystic change in adenocarcinoma of the prostate is unusual and may be confused with benign cystic atrophy. Limited data exist on the pathologic attributes of microcystic change in malignant prostatic glands. The aim of this study was to assess histologic and immunohistologic characteristics of microcystic adenocarcinoma of the prostate. This alteration was defined as cystic dilatation and rounded expansion of the malignant gland profile, with a flat luminal cell lining layer. We identified 53 cases with microcystic change from a survey of 472 radical prostatectomy cases, for an incidence of 11.2%. The greatest diameter of the dilated cancer glands was 0.4 to 0.9 mm, with a mean diameter 10-fold greater than adjacent small malignant glands. The microcystic glands were typically adjacent to usual small acinar adenocarcinoma. Atrophic features were seen at least focally in all cases, although many microcystic adenocarcinoma epithelia exhibited a moderate amount of cytoplasm. Gleason grade 3 was the predominant grade of the adjacent nonmicrocystic malignant glands. Intraluminal crystalloids, and wispy blue intraluminal mucin were seen in all cases. Ninety-six percent of the microcystic cases showed alpha-methylacyl CoA racemase overexpression and all cases showed complete basal cell loss (using 34betaE12 and p63 antibodies) in immunohistochemistry. Microcystic adenocarcinoma of the prostate is a distinctive histomorphologic presentation of prostatic adenocarcinoma that is deceptively benign-looking at low magnifications. Detection of intraluminal crystalloids or wispy blue mucin at low magnification, immunostains for alpha-methylacyl CoA racemase, and basal cells, and a search for adjacent usual small acinar adenocarcinoma are helpful diagnostic aids. Diagnostic awareness of this growth pattern of prostatic carcinoma is important to avoid underdiagnosis of adenocarcinoma of the prostate.
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PMID:Microcystic adenocarcinoma of the prostate: a variant of pseudohyperplastic and atrophic patterns. 2021 81


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