Dataset Information

Human kallikrein-2 gene and protein expression predicts prostate cancer at repeat biopsy.

ABSTRACT: PURPOSE:The human kallikrein-2 (hK2) protein and two single nucleotide polymorphism (SNPs) (rs2664155, rs198977) of the gene are associated with prostate cancer risk. We examined whether hK2 protein and gene SNPs predict prostate cancer at the time of repeat biopsy. METHODS:We prospectively offered a repeat biopsy to men with a negative prostate biopsy performed for a PSA >4.0 ng/mL or abnormal Digital Rectal Exam (DRE) between 2001-2005. We genotyped and measured serum hK2 levels in 941 men who underwent a repeat prostate biopsy. Logistic regression analyses were conducted to determine the significance of KLK2 SNPs and hK2 levels for predicting cancer at repeat biopsy. RESULTS:Of the 941 patients, 180 (19.1%) were found to have cancer. The rs198977 SNP was positively associated with cancer at repeat biopsy (OR variant T allele?=?1.8, 95% CI: 1.04-3.13, p?=?0.049). When combined, the odds ratio for prostate cancer for patients with high hK2 levels and the variant T-allele of rs198977 was 3.77 (95% CI: 1.94-7.32, p?

SUBMITTER: Satkunasivam R

PROVIDER: S-EPMC4162525 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Human kallikrein-2 gene and protein expression predicts prostate cancer at repeat biopsy.

Satkunasivam Raj R Zhang William W Trachtenberg John J Toi Ants A Yu Changhong C Diamandis Eleftherios E Kattan Michael W MW Narod Steven A SA Nam Robert K RK

SpringerPlus 20140611

<h4>Purpose</h4>The human kallikrein-2 (hK2) protein and two single nucleotide polymorphism (SNPs) (rs2664155, rs198977) of the gene are associated with prostate cancer risk. We examined whether hK2 protein and gene SNPs predict prostate cancer at the time of repeat biopsy.<h4>Methods</h4>We prospectively offered a repeat biopsy to men with a negative prostate biopsy performed for a PSA >4.0 ng/mL or abnormal Digital Rectal Exam (DRE) between 2001-2005. We genotyped and measured serum hK2 levels ...[more]

PMID: 25279276

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Project description:INTRODUCTION: There is no consensus on how to investigate men with negative transrectal ultrasound guided prostate biopsy (TRUS-B) but ongoing suspicion of cancer. Three strategies used are transperineal (TP-B), transrectal saturation (TS-B) and MRI-guided biopsy (MRI-B). We compared cancer yields of these strategies. METHODS: Papers were identified by search of Pubmed, Embase and Ovid Medline. Included studies investigated biopsy diagnostic yield in men with at least one negative TRUS-B and ongoing suspicion of prostate cancer. Data including age, PSA, number of previous biopsy episodes, number of cores at re-biopsy, cancer yield, and Gleason score of detected cancers were extracted. Meta-regression analyses were used to analyse the data. RESULTS: Forty-six studies were included; 12 of TS-B, 14 of TP-B, and 20 of MRI-B, representing 4,657 patients. Mean patient age, PSA and number of previous biopsy episodes were similar between the strategies. The mean number of biopsy cores obtained by TP-B and TS-B were greater than MRI-B. Cancer detection rates were 30·0%, 36·8%, and 37·6% for TS-B, TP-B, and MRI-B respectively. Meta-regression analysis showed that MRI-B had significantly higher cancer detection than TS-B. There were no significant differences however between MRI-B and TP-B, or TP-B and TS-B. In a sensitivity analysis incorporating number of previous biopsy episodes (36 studies) the difference between MRI-B and TP-B was not maintained resulting in no significant difference in cancer detection between the groups. There were no significant differences in median Gleason scores detected comparing the three strategies. CONCLUSIONS: In the re-biopsy setting, it is unclear which strategy offers the highest cancer detection rate. MRI-B may potentially detect more prostate cancers than other modalities and can achieve this with fewer biopsy cores. However, well-designed prospective studies with standardised outcome measures are needed to accurately compare modalities and define an optimum re-biopsy approach.

Project description:BackgroundIn men with clinically localized prostate cancer who have undergone at least 1 previous negative biopsy and have elevated serum prostate-specific antigen (PSA) levels, long-term health outcomes associated with the assessment of urinary prostate cancer antigen 3 (PCA3) and the transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG) have not been investigated previously in relation to the decision to recommend a repeat biopsy.MethodsThe authors performed a decision analysis using a decision tree for men with elevated PSA levels. The probability of cancer was estimated using the Prostate Cancer Prevention Trial Risk Calculator (version 2.0). The use of PSA alone was compared with the use of PCA3 and T2:ERG scores, with each evaluated independently, in combination with PSA to trigger a repeat biopsy. When PCA3 and T2:ERG score evaluations were used, predefined thresholds were established to determine whether the patient should undergo a repeat biopsy. Biopsy outcomes were defined as either positive (with a Gleason score of <7, 7, or >7) or negative. Probabilities and estimates of 10-year overall survival and 15-year cancer-specific survival were derived from previous studies and a literature review. Outcomes were defined as age-dependent and Gleason score-dependent 10-year overall and 15-year cancer-specific survival rates and the percentage of biopsies avoided.ResultsIncorporating the PCA3 score (biopsy threshold, 25; generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA) or the T2:ERG score (biopsy threshold, 10; based on the urine T2:ERG level normalized to the amount of PSA messenger RNA) into the decision to recommend repeat biopsy would have avoided 55.4% or 64.7% of repeat biopsies for the base-case patient, respectively, and changes in the 10-year survival rate were only 0.93% or 1.41%, respectively. Multi-way sensitivity analyses suggested that these results were robust with respect to the model parameters.ConclusionsThe use of PCA3 or T2:ERG testing for repeat biopsy decisions can substantially reduce the number of biopsies without significantly affecting 10-year survival.

Dataset Information

Human kallikrein-2 gene and protein expression predicts prostate cancer at repeat biopsy.

Publications

Human kallikrein-2 gene and protein expression predicts prostate cancer at repeat biopsy.

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