scholarly journals Increased serum level of early prostate cancer antigen is associated with subsequent cancer risk in men with high-grade prostatic intraepithelial neoplasia

2010 ◽  
Vol 17 (2) ◽  
pp. 505-512 ◽  
Author(s):  
Zhigang Zhao ◽  
Guohua Zeng
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Intraepithelial Neoplasia ◽  
Prostatic Intraepithelial Neoplasia ◽  
High Grade ◽  
Cancer Antigen ◽  
Early Prostate Cancer ◽  
Prostate Cancer Antigen ◽  
Subsequent Cancer

Early prostate cancer antigen (EPCA) has been recently suggested as a novel biomarker in malignant and premalignant lesions of the prostate. This study was to examine serum expression of EPCA and to further clarify the relationship between initial serum EPCA levels and the presence of subsequent cancer in the individuals with isolated high-grade prostatic intraepithelial neoplasia (HGPIN). An indirect ELISA was used for initial serum EPCA measurement in 112 men with isolated HGPIN, who were enrolled and completed a follow-up of ≥5 years. All patients had a detectable concentration of EPCA in the initial serum, with a mean of 0.64±0.13 absorbance at 450 nm. Thirty-three patients had an initial serum EPCA level of ≥1.10, in which 31 cases were subsequently identified as having prostate cancer on follow-up. However, in the remaining 79 cases, serum EPCA levels were all <1.10, and none was diagnosed with cancer later. Statistical analysis showed a significantly higher serum ECPA level in isolated HGPIN patients with subsequent cancer than those without cancer (P<0.001). The area under the receiver operating characteristic curves showed that serum EPCA level had better predictive accuracy of cancer onset on follow-up than prostate specific antigen velocity and abnormal digital rectal examination findings. Furthermore, univariate and multivariate Cox regression analyses demonstrated the predictive performance independently by initial serum EPCA≥1.10 absorbance (relative risk, 3.32; 95% confidence intervals, 2.62–5.03, P<0.001). These preliminary findings first show the potential of serum EPCA to serve as a significant predictor for subsequent cancer in isolated HGPIN.

scholarly journals Subsequent prostate cancer detection in patients with prostatic intraepithelial neoplasia or atypical small acinar proliferation

2012 ◽  
Vol 1 (3) ◽  
Author(s):  
Moamen A. Amin ◽  
Suganthiny Jeyaganth ◽  
Nader Fahmy ◽  
Louis Bégin ◽  
Samuel Aronson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Detection ◽  
Specific Antigen ◽  
Intraepithelial Neoplasia ◽  
Prostatic Intraepithelial Neoplasia ◽  
Atypical Small Acinar Proliferation ◽  
Psa Density ◽  
Significant Difference ◽  
Initial Biopsy

Introduction: To evaluate the predictors of prostate cancer in follow-up of patientsdiagnosed on initial biopsy with high-grade prostatic intraepithelial neoplasia(HGPIN) or atypical small acinar proliferation (ASAP).Methods: We studied 201 patients with HGPIN and 22 patients with ASAPon initial prostatic biopsy who had subsequent prostatic biopsies. The meantime of follow-up was 17.3 months (range 1–62). The mean number of biopsy sessions was 2.5 (range 2–6), and the median number of biopsy cores was10 (range 6–14).Results: On subsequent biopsies, the rate of prostate cancer was 21.9% (44/201)in HGPIN patients. Of these, 32/201 patients (15.9%), 9/66 patients (13.6%)and 3/18 patients (16.6%) were found to have cancer on the first, second and third follow-up biopsy sessions, respectively. In ASAP patients, the cancer detectionrate was 13/22 (59.1%), all of whom were found on the first follow-upbiopsy. There was a statistically significant difference between the cancer detectionrate in ASAP and HGPIN patients (p < 0.001). Multivariate analysis showedthat the independent predictors of cancer were the number of cores in theinitial biopsy, the number of cores (> 10) in the follow-up biopsy and a prostate specific antigen (PSA) density of ≥ 0.15 (odds ratio 0.77, 3.46 and 2.7,8 respectively;p < 0.04). Conversely, in ASAP patients none of these variables werefound to be associated with cancer diagnosis.Conclusion: ASAP is a strong predictive factor associated with cancer when comparedwith HGPIN. The factors predictive of cancer on follow-up biopsy ofHGPIN are number of cores on initial biopsy, more than 10 cores in rebiopsyand elevated PSA density. As the cancer detection rate on repeated biopsy of HGPIN patients is the same as that of patients without HGPIN, perhaps the standard of repeat biopsy in all patients with HGPIN should be revisited.

scholarly journals Antibody-Based Detection of ERG Rearrangements in Prostate Core Biopsies, Including Diagnostically Challenging Cases: ERG Staining in Prostate Core Biopsies

2012 ◽  
Vol 136 (8) ◽  
pp. 935-946 ◽  
Author(s):  
Scott A. Tomlins ◽  
Nallasivam Palanisamy ◽  
Javed Siddiqui ◽  
Arul M. Chinnaiyan ◽  
Lakshmi P. Kunju
Keyword(s):  
Prostate Cancer ◽  
In Situ Hybridization ◽  
Retrospective Cohort ◽  
Intraepithelial Neoplasia ◽  
Prostatic Intraepithelial Neoplasia ◽  
High Grade ◽  
Diagnosis Of Cancer ◽  
Prostate Cancers ◽  
Subsequent Cancer

Context.—Fusions of androgen-regulated genes and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) occur in approximately 50% of prostate cancers, encoding a truncated ERG product. In prostatectomy specimens, ERG rearrangements are greater than 99% specific for prostate cancer or high-grade prostatic intraepithelial neoplasia adjacent to ERG-rearranged prostate cancer by fluorescence in situ hybridization and immunohistochemistry. Objective.—To evaluate ERG staining by immunohistochemistry on needle biopsies, including diagnostically challenging cases. Design.—Biopsies from a retrospective cohort (n  =  111) enriched in cores requiring diagnostic immunohistochemistry and a prospective cohort from all cases during 3 months (n  =  311) were stained with an anti-ERG antibody (clone EPR3864). Results.—Among evaluable cores (n  =  418), ERG staining was confined to cancerous epithelium (71 of 160 cores; 44%), high-grade prostatic intraepithelial neoplasia (12 of 68 cores; 18%), and atypical foci (3 of 28 cores; 11%), with staining in only 2 of 162 cores (1%) diagnosed as benign. The ERG was expressed in about 5 morphologically benign glands across 418 cores and was uniformly expressed by all cancerous glands in 70 of 71 cores (99%). Conclusions.—ERG staining is more prostate cancer–specific than α-methylacyl-coenzyme A racemase, and staining in an atypical focus supports a diagnosis of cancer if high-grade prostatic intraepithelial neoplasia can be excluded. Thus, ERG staining shows utility in diagnostically challenging biopsies and may be useful in molecularly subtyping prostate cancer and in stratifying isolated high-grade prostatic intraepithelial neoplasia by risk of subsequent cancer.

scholarly journals TMPRSS2:ERG Gene Fusion Predicts Subsequent Detection of Prostate Cancer in Patients With High-Grade Prostatic Intraepithelial Neoplasia

2014 ◽  
Vol 32 (3) ◽  
pp. 206-211 ◽  
Author(s):  
Kyung Park ◽  
James T. Dalton ◽  
Ramesh Narayanan ◽  
Christopher E. Barbieri ◽  
Michael L. Hancock ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Gene Fusion ◽  
Intraepithelial Neoplasia ◽  
Prostatic Intraepithelial Neoplasia ◽  
Phase Iii ◽  
High Grade ◽  
Exact Test ◽  
Improve Risk Stratification

Purpose High-grade prostatic intraepithelial neoplasia (HGPIN) is considered a precursor lesion of prostate cancer (PCa). The predictive value of ERG gene fusion in HGPIN for PCa was interrogated as a post hoc analysis in the context of a randomized clinical trial. Patients and Methods The GTx Protocol G300104 randomly assigned 1,590 men with biopsy-diagnosed HGPIN to receive toremifene or placebo for 3 years or until a diagnosis of PCa was made on prostate biopsy. As part of this phase III clinical trial, a central pathologist evaluated biopsies of patients with isolated HGPIN at baseline and 12, 24, and 36 months of follow-up. ERG immunohistochemistry was performed on biopsies from 461 patients and evaluated for protein overexpression. Results ERG expression was detected in 11.1% of patients (51 of 461 patients) with isolated HGPIN. In the first year and during the 3-year clinical trial, 14.7% and 36.9% of 461 patients were diagnosed with PCa, respectively. Patients with ERG expression were more likely to develop PCa, with 27 (53%) of 51 ERG-positive and 143 (35%) of 410 ERG-negative patients experiencing progression to PCa (P = .014, Fisher's exact test). ERG expression was not associated with age, baseline PSA, Gleason score, or tumor volume. Conclusion This study underscores the necessity of more stringent follow-up for men with HGPIN that is also positive for ERG overexpression. Clinicians should consider molecular characterization of HGPIN as a means to improve risk stratification.

Effects of Lycopene Supplementation in Patients with Localized Prostate Cancer

2002 ◽  
Vol 227 (10) ◽  
pp. 881-885 ◽  
Author(s):  
Omer Kucuk ◽  
Fazlul H. Sarkar ◽  
Zora Djuric ◽  
Wael Sakr ◽  
Michael N. Pollak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Dietary Intake ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Intervention Group ◽  
Intraepithelial Neoplasia ◽  
Prostatic Intraepithelial Neoplasia ◽  
Control Group ◽  
High Grade

Epidemiological studies have shown an inverse association between dietary intake of lycopene and prostate cancer risk. We conducted a clinical trial to investigate the biological and clinical effects of lycopene supplementation in patients with localized prostate cancer. Twenty-six men with newly diagnosed prostate cancer were randomly assigned to receive a tomato oleoresin extract containing 30 mg of lycopene (n = 15) or no supplementation (n = 11) for 3 weeks before radical prostatectomy. Biomarkers of cell proliferation and apoptosis were assessed by Western blot analysis in benign and cancerous prostate tissues. Oxidative stress was assessed by measuring the Peripheral blood lymphocyte ONA oxidation product 5-hydroxymethyl-deoxyuridine (5-OH-mdU). Usual dietary Intake of nutrients was assessed by a food frequency questionnaire at baseline. Prostatectomy specimens were evaluated for pathologic stage, Gleason score, volume of cancer, and extent of high-grade prostatic intraepithelial neoplasia. Plasma levels of lycopene, insulin-like growth factor-1, insulin-like growth factor binding protein-3, and prostate-specific antigen were measured at baseline and after 3 weeks of supplementation or observation. After intervention, subjects in the intervention group had smaller tumors (80% vs 45%, less than 4 ml), less involvement of surgical margins and/or extra-prostatic tissues with cancer (73% vs 18%, organ-confined disease), and less diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia (33% vs 0%, focal involvement) compared with subjects in the control group. Mean plasma prostate-specific antigen levels were lower in the intervention group compared with the control group. This pilot study suggests that lycopene may have beneficial effects in prostate cancer. Larger clinical trials are Warranted to investigate the potential preventive and/or therapeutic role of lycopene in prostate cancer.

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