PubMed Health⌕ Search

Biomedical subjects

Mark A Rubin

Publications and source records attributed to Mark A Rubin.

At least 73 records · Page 4Linked to original sources

Effect of finasteride on risk of prostate cancer: how little we really know.

The Prostate Cancer Prevention Trial (PCPT) reported conclusively that finasteride prevents or delays the detection of prostate cancer. One perplexing finding was that more high-grade tumors were detected in the finasteride treated group. It is hard to put this into perspective because of the limited published data on the effects of finasteride on prostate cancer. The strong possibility exists that the increase in high-grade tumors may be due to a treatment effect, which causes intermediate grade cancers to appear to be high-grade or aggressive tumors. Confirmation of a spurious tumor grade "inflation" will make the conclusions of this study clearer and define the benefits of finasteride chemoprevention in a more favorable light.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

The role of metastasis-associated protein 1 in prostate cancer progression.

Distinguishing aggressive prostate cancer from indolent disease represents an important clinical challenge, as current therapy requires over treating men with prostate cancer to prevent the progression of a few cases. Expression of the metastasis-associated protein 1 (MTA1) has previously been found to be associated with progression to the metastatic state in various cancers. Analyzing DNA microarray data, we found MTA1 to be selectively overexpressed in metastatic prostate cancer compared with clinically localized prostate cancer and benign prostate tissue. These results were validated by demonstrating overexpression of MTA1 in metastatic prostate cancer by immunoblot analysis. MTA1 protein expression was evaluated by immunohistochemistry in a broad spectrum of prostate tumors with tissue microarrays containing 1940 tissue cores from 300 cases. Metastatic prostate cancer demonstrated significantly higher mean MTA1 protein expression intensity (score = 3.4/4) and percentage of tissue cores staining positive for MTA1 (83%) compared with clinically localized prostate cancer (score = 2.8/4, 63% positive cores) or benign prostate tissue (score = 1.5/4, 25% positive cores) with a mean difference of 0.54 and 1.84, respectively (P < 0.00001 for both). Paradoxically, for localized disease, higher MTA1 protein expression was associated with lower rates of prostate specific antigen recurrence after radical prostatectomy for localized disease. In summary, this study identified an association of MTA1 expression and prostate cancer progression.

Adult↗

Molecular profiling and the identification of genes associated with metastatic oral cavity/pharynx squamous cell carcinoma.

OBJECTIVE: To investigate differences in gene expression profiles between oral cavity/oropharynx squamous cell carcinoma (OC/OP SCC) primary tumors that have metastasized to cervical lymph nodes and nonmetastatic OC/OP SCC tumors. DESIGN: Oligonucleotide microarray analysis of primary tumors was used to produce gene expression profiles. Profile comparisons between metastatic and nonmetastatic tumors were performed using principal component analysis, t test, and fold change differences. A similar comparison between metastatic tumors and noncancer oral mucosa samples was performed to ensure tumor origin. SUBJECTS: A prospective cohort of 20 patients with previously untreated OC/OP SCC who underwent pathologic staging following surgical resection and lymphadenectomy. RESULTS: Of the approximately 9600 genes profiled, 101 demonstrated significant expression differences between the metastatic and nonmetastatic tumors (fold change > or =1.5; P<.01). Among this subset, 57 genes also exhibited significant differences between metastatic tumors and normal mucosa samples (fold change > or =1.5; P<.05). This profile included genes related to the extracellular matrix, adhesion, motility, inflammation, and protease inhibition. Collagen type 11 alpha-1 (COL11A1) demonstrated the greatest differential expression between metastatic and nonmetastatic OC/OP SCC tumors (fold change=7.61; P=.002). Tissue inhibitor of metalloproteinase 1 (TIMP-1) also demonstrated increased expression in metastatic tumors (fold change=3.3; P=.003). CONCLUSIONS: Metastatic OC/OP SCC has a distinct gene expression profile compared with nonmetastatic OC/OP SCC and normal oral mucosa. This metastatic profile includes genes related to the extracellular matrix, adhesion, motility, and protease inhibition. Knowledge gained through tumor gene expression profiling may facilitate early detection of aggressive tumors and targeted therapeutic interventions.

Carcinoma, Squamous Cell↗

Prospective evaluation of AMACR (P504S) and basal cell markers in the assessment of routine prostate needle biopsy specimens.

Distinguishing benign prostate glands from malignant ones, based purely on morphology, on prostatic core needle biopsy specimens (PNBs) may prove difficult, particularly if the suspicious focus is small. In recent years, several immunohistochemical markers, including the basal cell cocktail (BCC), 34betaE12 and p63, and the prostate cancer (PCa) biomarker alpha-methylacyl-CoA-racemase (AMACR), have been used as adjuvants to morphology, in these diagnostically challenging cases. We prospectively address the diagnostic utility of using the BCC, in combination with the commercially available AMACR monoclonal antibody, P504S, on PNBs that required immunohistochemistry (IHC) studies to make a diagnosis. The goals of this prospective study were to assess the day-to-day practice in an academic setting, to determine how often these IHC tests were used on routine PNBs, and to establish how often a combination of the BCC and P504S were helpful in diagnosing prostate cancer. A total of 772 prospectively collected PNB cases were examined over a 7-month period. IHC staining was performed in 171 cases (22%); 123 cases were stained with the BCC in addition to the commercially available monoclonal AMACR antibody. In 86 of these 123 cases (70%), both stains contributed to the final diagnosis: PCa in 44 cases, benign in 33 cases and high-grade prostatic intraepithelial neoplasia in 9 cases. Of the remaining 37 cases (30%), 18 were called benign or PCa, based solely on appropriate staining with the BCC, with AMACR being noncontributory because the focus of interest had been cut through (12 cases), there was negative staining with AMACR (in 4 PCa cases), or there was positive staining with AMACR (in 2 benign cases showing atrophy). Nineteen of 37 cases were diagnosed as atypical small acinar proliferation. In these 19 cases either the focus had been cut through on one or both of the stains (11 cases), both AMACR and BCC failed to work (2 cases), AMACR was positive in the presence of patchy BCC staining (1 cases), AMACR was negative in the absence of BCC staining (3 cases), or despite appropriate staining the focus consisted of 1 gland and was considered too small to call carcinoma (2 cases). Additional IHC stains were performed in 171 of 772 cases; of these, 123 had sufficient material to perform both the BCC and P504S. The BCC when used in combination with AMACR rendered a diagnosis in almost 70% of cases. Using these stains in combination may be a better approach in diagnostically difficult cases as it increases the likelihood that a definitive diagnosis can be rendered while decreasing the likelihood of an equivocal diagnosis. However, a limitation of this approach is the loss of tissue in these small lesions, suggesting that combining AMACR and the BCC on a single slide would be superior to using either marker separately.

Adenocarcinoma↗

Elevated alpha-methylacyl-CoA racemase enzymatic activity in prostate cancer.

Alpha-methylacyl-CoA racemase (AMACR) is a peroxisomal and mitochondrial enzyme involved in the beta-oxidation of branched fatty acids, shown to be elevated in prostate cancer by several recent studies. Sequence variants of AMACR have been linked to prostate cancer risk. Although mRNA transcript, protein, and sequence variants of AMACR have been studied in the context of prostate cancer, AMACR enzymatic activity has not been addressed. Here we present evidence that AMACR activity is consistently elevated in prostate cancer tissue specimens. This activity can be immunodepleted from prostate cancer tissue extracts. Furthermore, mock needle biopsy cores containing foci of prostate cancer exhibited increased AMACR enzymatic activity, correlating with both protein levels and histopathology. Taken together, our studies suggest that AMACR activity is increased in prostate cancer relative to benign epithelia and suggests that monitoring AMACR activity levels in prostate needle biopsies may have clinical applications.

Biomarkers, Tumor↗

Quantitative determination of expression of the prostate cancer protein alpha-methylacyl-CoA racemase using automated quantitative analysis (AQUA): a novel paradigm for automated and continuous biomarker measurements.

Despite years of discovery and attempts at validation, few molecular biomarkers achieve acceptance in the clinical setting. Tissue-based markers evaluated by immunohistochemistry suffer from a high degree of inter- and intraobserver variability. One recent advance in this field that promises to automate this process is the development of AQUA, a molecular-based method of quantitative assessment of protein expression. This system integrates a set of algorithms that allows for the rapid, automated, continuous, and quantitative analysis of tissue samples, including the separation of tumor from stromal elements and the subcellular localization of signals. This study uses the AQUA system to assess a recently described prostate cancer biomarker, alpha-methylacyl-CoA-racemase (AMACR), and to determine the effectiveness of the quantitative measurement of this marker as a means for making the diagnosis of prostate cancer. Using a prostate cancer progression tissue microarray containing a wide range of prostate tissues, AQUA was directly compared to standard immunohistochemical evaluation for AMACR protein expression using the p504s monoclonal antibody. Both methods produced similar results showing AMACR protein expression to be strongest in the clinically localized prostate cancer, followed by the metastatic tumor samples. Benign prostate tissue was categorized as negative for most tissue samples by immunohistochemistry. However, AMACR was detectable using the AQUA system at low levels using the standard 1:25 dilution but also at 1:250 dilution, which is not detectable by light microscopy. The AQUA system was also able to discriminate foamy gland prostate cancers, which are known to have a lower AMACR expression than typical acinar prostate cancers, from benign prostate tissue samples. Finally, a receiver-operating-characteristic curve was plotted to determine the specificity of the AMACR AQUA Z-score (normalized AQUA score) to predict that a given tissue microarray sample contains cancer. The area under the curve was calculated at 0.90 (P < 0.00001; 95% CI, 0.84 to 0.95). At an AMACR AQUA Z-score score of -0.3, 91% of the 70 samples classified as prostate cancer were correctly categorized without the intervention of a pathologist reviewing the tissue microarray slide. In conclusion, the AQUA system provides a continuous measurement of AMACR on a wide range of prostate tissue samples. In the future, the AMACR AQUA Z-score may be useful in the automated screening and evaluation of prostate tissue biomarkers.

Biomarkers, Tumor↗

Molecular genetics of human prostate cancer.

Multiple factors contribute to the high incidence and prevalence of prostate cancer including race, ethnicity, diet, environment, widespread awareness through prostate-specific antigen screening and genetics. Linkage analysis has identified several candidate sites for hereditary prostate cancer gene loci. Molecular studies have also identified genes that are frequently altered in sporadic prostate cancer. It appears that due to the heterogeneity of prostate cancer, multiple genes may be involved in the neoplastic process.

Chromosomal Instability↗

Prostate needle biopsy reporting: how are the surgical members of the Society of Urologic Oncology using pathology reports to guide treatment of prostate cancer patients?

Recent trends in prostate needle biopsy reporting have resulted in the inclusion of more information and new diagnostic categories. The goal of the current study was to survey surgical Members of the Society of Urologic Oncology to determine what information academic urologists consider important in the management of their prostate cancer (PCa) patients. A questionnaire was developed to investigate several areas of PCa biopsy reporting, which vary from institution to institution. Urologists were sent questionnaires and asked to return anonymous responses; 42 questionnaires were completely evaluated with a response rate of 76% (42 of 55). The urologists targeted for this survey were highly experienced with an average of 22 years in clinical practice (range, 6-35 years). On average, they performed 92 radical prostatectomies per year and 449 over the past 5 years (range, 60-1500) for a group total of 18,840 radical prostatectomies; 94% have their patient's biopsy reviewed prior to surgery. The primary and secondary Gleason pattern was required by 60% (25 of 42) of the respondents. In prostate needle biopsies containing only a single minute focus of PCa, only 41% (17 of 42) of respondents would request a Gleason score if not provided in the initial report. Interestingly, in biopsies with multiple positive cores from separate locations, 81% (34 of 42) use the highest Gleason score, regardless of the overall percentage involvement, to determine their treatment plan. Other pathology parameters requested by the respondents in descending order included: % involvement of the core by PCa (67%), the presence or absence of perineural invasion (38%), the number of cores with PCa (33%), and the length of core involvement (29%). Only 24% (10 of 42) of respondents use perineural invasion status to guide nerve-sparing surgery. The more radical prostatectomies performed by a surgeon, the greater the likelihood that they considered perineural invasion clinically important (Mann-Whitney, two-tailed, P = 0.015). The term atypical small acinar proliferation was uniformly considered sufficient to re-biopsy by 98% (41 of 42) of the urologists. This is the first study to survey urologists as to what information they require from prostate needle biopsy reports in their treatment planning of men with clinically localized PCa. With the exception of Gleason score, the use of detailed pathology information was variably used to guide treatment. PNI was not considered important by the majority of respondents. In contrast, atypical small acinar proliferation, a more recent diagnostic category, was recognized as important by nearly all respondents. Knowledge of how pathology biopsy reports are being used should help evaluate what data should be uniformly part of standard biopsy pathology report and help improve communication between pathologists and urologists.

Attitude of Health Personnel↗

Using molecular markers to predict outcome.

PURPOSE: Developing molecular tests to predict prostate cancer progression requires first defining meaningful clinical end points and defining strategies to take advantage of emerging technology. MATERIALS AND METHODS: The select relevant literature was reviewed concerning clinical trials, clinical prostate cancer nomograms, molecular biomarker development and molecular prostate cancer imaging. RESULTS: There is controversy regarding the use of prostate specific antigen or biochemical failure following prostatectomy or radiation therapy for clinically localized prostate cancer as a marker of progression. As a consequence, advances in prostate cancer biomarker development may require using population based cohorts or cases from clinical trials to identify meaningful associations. Whereas the discovery of novel candidate biomarkers was slow 5 to 10 years ago and often resulted from serendipity, advances in high throughput technologies have led to the identification of a large number of candidate genes. Strategies to identify candidate genes include the use of expression array analysis, single nucleotide polymorphism arrays (single nucleotide polymorphism chips), proteomics and bioinformatics. Monitoring the progression of prostate cancer has been limited to standard approaches such as computerized tomography or magnetic resonance imaging, which in general do not delineate the extent of disease. By carefully selecting novel prostate cancer biomarkers future work should allow in vivo monitoring of prostate cancer. This will represent a revolutionary advance in our ability to monitor prostate cancer progression and ultimately it may be one of the most important applications of cancer biomarkers. CONCLUSIONS: Emerging technology should allow us to analyze clinical prostate cancer trials with sufficient followup to help develop meaningful markers of prostate cancer progression.

Biomarkers, Tumor↗

Usefulness of basal cell cocktail (34betaE12 + p63) in the diagnosis of atypical prostate glandular proliferations.

We evaluated the diagnostic usefulness of the 34betaE12-p63 cocktail, compared with 34betaE12 and p63 used alone, in 34 prostate needle biopsy (NBXs) and 3 transurethral resection specimens containing atypical glandular proliferations and in 18 NBXs containing unequivocal prostate carcinoma (PCa). Staining intensity; percentage of basal cells staining in benign, atypical, and malignant glands; number of benign glands lacking basal cell staining; and staining variance were analyzed. All NBXs with unequivocal PCa were negative with all 3 markers. Diagnoses were as follows for the atypical cases after staining for the 3 markers: PCa, 9; postatrophic hyperplasia, 12; high-grade prostatic intraepithelial neoplasia (HGPIN), 5; atypical adenomatous hyperplasia, 6; benign atypical proliferations, 4; and HGPIN with adjacent small atypical acinar proliferation suggestive of PCa, 1. The cocktail demonstrated consistently strong staining intensity and improved basal cell staining in morphologically benign and benign atypical glands compared with p63 and 34betaE12 alone; it had the smallest staining variance compared with 34betaE12 (F < 0.0001) and p63 (F = 0.31), although its advantage for resolving individual atypical cases was limited compared with 34betaE12 and p63 alone. Of 37 atypical cases, 1 (3%) additionally was resolved as benign using the cocktail and p63. Because the diagnosis of PCa is supported by lack of basal cell staining, the immunohistochemical analysis with highest possible sensitivity and lowest possible variability is critical to ensure that a negative reaction is true. The cocktail provides a simple, cost-effective improvement in basal cell immunohistochemical analysis of difficult prostate lesions.

Biomarkers, Tumor↗

The role of an 80 kDa fragment of E-cadherin in the metastatic progression of prostate cancer.

PURPOSE: The purpose of this study was to evaluate an 80 kDa proteolytic fragment of E-cadherin as a potential biomarker for prostate cancer progression and to identify putative proteases that are responsible for the cleavage of E-cadherin. EXPERIMENTAL DESIGN: A wide spectrum of prostate cancer tissue and serum specimens representing different stages of prostate cancer was examined for the accumulation of the 80 kDa fragment of E-cadherin. Additionally, an expression array analysis was used to identify putative proteases that may have been involved in the cleavage of E-cadherin. RESULTS: A reproducible E-cadherin fragment was detected as a strong 80 kDa band in tissue samples. This fragment was detectable almost exclusively in metastatic sites. It was not visible in normal prostate tissue and was weak in 1 of 16 localized prostate cancers. The fragment is shed into the extracellular space and was detectable in patient serum in which the expression of the fragment showed a strong association with advanced prostate cancer. On the basis of cDNA expression analysis, several members of the metalloproteinase family could be identified as potentially responsible for the cleavage of the fragment from full-length E-cadherin. CONCLUSIONS: In this study, we present the first report of serum levels of the 80 kDa fragment of E-cadherin in prostate cancer patients. This fragment is exclusively seen in neoplastic prostate tissue and may represent a useful biomarker of prostate cancer disease progression. This study also demonstrates an association of increased levels of several metalloproteinases with metastatic prostate cancer and could provide a useful correlation between metalloproteinase expression/activity and E-cadherin cleavage and the metastatic progression of prostate cancer.

Blotting, Western↗

E-cadherin expression in primary carcinomas of the breast and its distant metastases.

INTRODUCTION: Aberrant expression of E-cadherin has been associated with the development of metastases in patients with breast cancer. Even though the expression of E-cadherin has been studied in primary breast tumors, little is known about its expression at the distant metastatic sites. We investigate the relationship between E-cadherin expression in primary breast carcinoma and their distant, non-nodal metastases. METHODS: Immunohistochemical analysis of E-cadherin was performed in tissues from 30 patients with primary invasive breast carcinoma and their distant metastases. E-cadherin expression was evaluated as normal or aberrant (decreased when compared with normal internal positive controls, or absent). RESULTS: Twenty-two (73%) invasive carcinomas were ductal, and eight (27%) were lobular. Of the primary invasive ductal carcinomas, 55% (12/22) had normal E-cadherin expression and 45% (10/22) had aberrant expression. All of the metastases expressed E-cadherin with the same intensity as (12 tumors) or with stronger intensity than (10 tumors) the corresponding primaries. Of the invasive lobular carcinomas, one of eight (12%) primary carcinomas and none of the metastases expressed E-cadherin in the cell membranes, but they accumulated the protein in the cytoplasm. CONCLUSION: Aberrant E-cadherin expression is frequent in invasive ductal carcinomas that progress to develop distant metastases. Distant metastases consistently express E-cadherin, often more strongly than the primary tumor. Invasive lobular carcinomas have a different pattern of E-cadherin expression, suggesting a different role for E-cadherin in this form of breast carcinoma.

Adult↗

EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells.

The Polycomb Group Protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive prostate cancer. Here we investigate the functional role of EZH2 in cancer cell invasion and breast cancer progression. EZH2 transcript and protein were consistently elevated in invasive breast carcinoma compared with normal breast epithelia. Tissue microarray analysis, which included 917 samples from 280 patients, demonstrated that EZH2 protein levels were strongly associated with breast cancer aggressiveness. Overexpression of EZH2 in immortalized human mammary epithelial cell lines promotes anchorage-independent growth and cell invasion. EZH2-mediated cell invasion required an intact SET domain and histone deacetylase activity. This study provides compelling evidence for a functional link between dysregulated cellular memory, transcriptional repression, and neoplastic transformation.

Breast↗

Effects of raf kinase inhibitor protein expression on suppression of prostate cancer metastasis.

BACKGROUND: Raf kinase inhibitor protein (RKIP), an inhibitor of Raf-mediated activation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK), is expressed at lower levels in human C4-2B metastatic prostate cancer cells than in the parental non-metastatic LNCaP prostate cancer cells from which they were derived. We examined whether RKIP functions as a suppressor of metastasis. METHODS: Immunohistochemistry was used to detect RKIP expression in clinical samples of primary prostate cancer and prostate cancer metastases. LNCaP and C4-2B cells were stably transfected with plasmids that constitutively expressed antisense and sense RKIP cDNA, respectively, or with empty vector. Assays of cell proliferation, soft-agar colony formation, and in vitro cell invasion were used to examine the malignant phenotypes of the transfected cells. An orthotopic murine model was used to examine the effect of expressing RKIP in C4-2B cells on the development of spontaneous metastasis. RESULTS: Clinical samples of primary prostate cancer had detectable RKIP expression, whereas clinical samples of prostate cancer metastases did not. There were no differences in the in vitro proliferation rate or colony-forming ability between the control vector-transfected and sense RKIP vector-transfected C4-2B cells or between the control vector-transfected and the antisense RKIP vector-transfected LNCaP cells. Overexpression of RKIP in C4-2B cells was associated with decreased in vitro cell invasion, decreased development of lung metastases in vivo, and decreased vascular invasion in the primary tumor but did not affect primary tumor growth in mice. CONCLUSIONS: RKIP does not influence the tumorigenic properties of human prostate cancer cells. It appears to be a novel and clinically relevant suppressor of metastasis that may function by decreasing vascular invasion.

Aged↗

Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo.

Human prostate cancers (PCa) express great variability in their ability to metastasize to bone. The identification of molecules associated with aggressive phenotypes will help to define PCa subsets and will ultimately lead to better treatment strategies. The chemokine stromal-derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are now known to modulate the migration and survival of an increasing array of normal and malignant cell types including breast, pancreatic cancers, glioblastomas, and others. The present investigation extends our previous investigations by determining the expression of CXCR4 and CXCL12 in humans using high-density tissue microarrays constructed from clinical samples obtained from a cohort of over 600 patients. These data demonstrate that CXCR4 protein expression is significantly elevated in localized and metastastic cancers. At the RNA level, human PCa tumors also express CXCR4 and message, but overall, they were not significantly different suggesting post-transcriptional regulation of the receptor plays a major role in regulating protein expression. Similar observations were made for CXCL12 message, but in this case more CXCL12 message was expressed by metastastic lesions as compared to normal tissues. PCa cell lines also express CXCL12 mRNA, and regulate mRNA expression in response to CXCL12 and secrete biologically active protein. Furthermore, neutralizing antibody to CXCL12 decreased the proliferation of bone homing LNCaP C4-2B and PC3 metastastic tumor cells. These investigations provide important new information pertaining to the molecular basis of how tumors may 'home' to bone, and the mechanisms that may account for their growth in selected end organs.

Adult↗

Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer.

BACKGROUND: Molecular signatures in cancer tissue may be useful for diagnosis and are associated with survival. We used results from high-density tissue microarrays (TMAs) to define combinations of candidate biomarkers associated with the rate of prostate cancer progression after radical prostatectomy that could identify patients at high risk for recurrence. METHODS: Fourteen candidate biomarkers for prostate cancer for which antibodies are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor samples from 259 patients who underwent radical prostatectomy for localized prostate cancer were studied with these antibodies. Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more than 0.2 ng/mL. All statistical tests were two-sided. RESULTS: Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer. EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). EZH2:ECAD status was statistically significantly associated with disease recurrence even after adjusting for clinical parameters, such as tumor stage, Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P =.003). CONCLUSION: EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence after radical prostatectomy and may be useful in defining a cohort of high-risk patients.

Adult↗