Dataset Information

Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy.

ABSTRACT: African-American (AA) men have a higher risk of lethal prostate cancer (PCa) compared to European-American (EA) men. However, the molecular basis of this difference, if any, remains unclear. In EA PCa, PTEN loss, but not ERG rearrangement, has been associated with poor outcomes in most studies. Although ERG rearrangement is less common in AA compared to EA PCa, the relative frequency of PTEN loss and the association of PTEN/ERG molecular subtypes with outcomes is unknown for AA PCa. We examined PTEN/ERG status by immunohistochemistry in self-identified AA patients undergoing radical prostatectomy at Johns Hopkins with tumor tissue available on tissue microarray (TMA; n=169) and matched these cases by pathologic parameters to 169 EA patients from the same TMAs. The rate of PTEN loss was significantly lower in AA compared to EA PCa (18% vs 34%; p=0.001), similar to the lower rate of ERG expression (25% vs 51%; p<0.001). To examine the association of PTEN/ERG status with oncologic outcomes, we created an additional TMA of 87 AA tumors with Gleason score > 4 + 3 = 7. Among the total population of AA men with outcome data from all TMAs (n=222), PTEN loss was associated with higher risk of biochemical recurrence (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33-3.82) and metastasis (HR 3.90, 95% CI 1.46-10.4) in multivariable models.PTEN and ERG alterations in prostate cancer are less likely in African-American than in European-American men. However, PTEN loss remains associated with poor prostate cancer outcomes among African-American men.

SUBMITTER: Tosoian JJ

PROVIDER: S-EPMC5274596 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy.

Tosoian Jeffrey J JJ Almutairi Fawaz F Morais Carlos L CL Glavaris Stephanie S Hicks Jessica J Sundi Debasish D Humphreys Elizabeth E Han Misop M De Marzo Angelo M AM Ross Ashley E AE Tomlins Scott A SA Schaeffer Edward M EM Trock Bruce J BJ Lotan Tamara L TL

European urology 20160728 5

African-American (AA) men have a higher risk of lethal prostate cancer (PCa) compared to European-American (EA) men. However, the molecular basis of this difference, if any, remains unclear. In EA PCa, PTEN loss, but not ERG rearrangement, has been associated with poor outcomes in most studies. Although ERG rearrangement is less common in AA compared to EA PCa, the relative frequency of PTEN loss and the association of PTEN/ERG molecular subtypes with outcomes is unknown for AA PCa. We examined ...[more]

PMID: 27477529

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Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Experiment Overall Design: A total of 69 fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens (n = 59) were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the specimens. These tissues were collected between 2002 and 2004 at four different sites, with each site providing tissues from both African-American and European-American patients. Information on race/ethnicity (33 African-Americans and 36 European-Americans) was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire in which race/ethnicity was self-reported (UMD). Only one patient, a European-American, was also Hispanic. Surrounding non-tumor prostate tissue was collected from 18 of the recruited patients in this study. Of those, 7 were African-American men and 11 were European-American men. We also isolated total RNA from 10 needle biopsy specimens collected from patients at the National Naval Medical Center (one African-American and 9 European-Americans) that did not have prostate cancer. From those, we prepared two RNA pools, each representing 5 patients. Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. Written informed consent was obtained from all donors. Tissue collection and study design were approved by the institutional review boards of the participating institutions.

Project description:BackgroundArousal incontinence (AI) occurs during physical or psychological sexual stimulation in men and has been described after radical prostatectomy (RP).AimThe goals of this study are to describe the characteristics of men experiencing AI, outline the nature of their symptoms, and assess for predictors of this condition.MethodsA survey with questions on AI, stress urinary incontinence (SUI), the International Index of Erectile Function and International Prostate Symptom Score were sent out to men who had undergone an RP within the past 24 months at a single institution. The data were deidentified and analyzed using descriptive statistics. Comparisons between men with and without AI were made using t-tests and χ2 and Fisher exact tests. Logistic regression in univariable and multivariable analyses were used to define predictors of AI.Main outcome measuresThe outcomes of this study included prevalence of AI, symptom severity and timing, patient and patient-perceived partner bother, management strategies used by the patients, and concurrent SUI.Results226 (32%) men completed the survey. Of these men, almost half (49%) experienced AI at some point during their recovery. Improvement over time was endorsed by 62% of men. 57% of men reported AI in less than half of the sexual encounters, with the amount of urine leakage being equivalent to a tablespoon or less in 88% of men. On univariate analysis, increasing degree of SUI, as measured by pads per day, was associated with AI (P = .01). A lower International Prostate Symptom Score was also associated (P = .05). On multivariate analysis, the absence of hypertension and pads per day were associated with AI (P = .01 for both).Clinical implicationsAI occurred in almost half of the respondents in our series. Thus, AI should be discussed with patients before surgery to allow for realistic expectations.Strengths & limitationsStrengths of this study include the largest patient population analyzed to date regarding AI and that it is the only one to address timing and patient experiences with the use of validated instruments for erectile and urinary function. Limitations include single-center data, non-validated AI patient-reported outcomes, and poor survey response rate.ConclusionBased on the available data, AI is reported by almost half of men after RP and is associated with SUI. Bach PV, Salter CA, Katz D, et al. Arousal Incontinence in Men Following Radical Prostatectomy: Prevalence, Impact and Predictors. J Sex Med 2020;16:1947-1952.

Dataset Information

Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy.

Publications

Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy.

Similar Datasets

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