Single Nucleotide Polymorphism of the Human Kallikrein-2 Gene Highly Correlates With Serum Human Kallikrein-2 Levels and in Combination Enhances Prostate Cancer Detection

2003 ◽  
Vol 21 (12) ◽  
pp. 2312-2319 ◽  
Author(s):  
Robert K. Nam ◽  
William W. Zhang ◽  
John Trachtenberg ◽  
Eleftherios Diamandis ◽  
Ants Toi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Wild Type ◽  
Patients With Cancer ◽  
Prostate Biopsies ◽  
Human Kallikrein 2 ◽  
Kallikrein 2

Purpose: We examined the relationship between a mutant (T) for wild-type (C) allele substitution of the human kallikrein-2 gene (KLK2), circulating human kallikrein-2 (hK2) levels and prostate cancer risk.Patients and Methods: We studied 1,287 consecutive men who underwent prostate biopsies because of an abnormal prostate-specific antigen level. Serum and DNA were obtained before biopsy. Cases were patients with cancer, and controls were patients with no cancer. The mutant and wild-type alleles of the KLK2 gene were designated as the T and C alleles, respectively.Results: Of the 1,287 men, 616 had cancer, and 671 had no cancer. The overall distribution of the CC, CT, and TT KLK2 genotypes was 55.1%, 38.2%, and 6.8%, respectively. The median hK2 levels for men with the CC, CT, and TT genotypes were 0.24, 0.18, and 0.062 ng/mL and correlated with the genotypes, respectively (P = .0001). The adjusted odds ratios for prostate cancer for patients with the TT and CT genotypes compared with patients with the CC genotype, were 2.13 (95% confidence interval [CI], 1.3 to 3.5; P = .004) and 1.51 (95% CI, 1.2 to 2.0; P = .002), respectively. The adjusted odds ratio for prostate cancer for patients in the fourth quartile of hK2 compared with the first quartile was 4.33 (95% CI, 2.9 to 6.4; P = .0001). When combined, the adjusted odds ratio for having prostate cancer was 13.92 (95% CI, 6.6 to 29.2; P = .0001) for patients with high hK2 levels and at least one T allele.Conclusion: The C/T polymorphism of the KLK2 gene and circulating levels of hK2 are correlated and, in combination, are highly predictive for prostate cancer.

scholarly journals Development of Sensitive Immunoassays for Free and Total Human Glandular Kallikrein 2

2004 ◽  
Vol 50 (9) ◽  
pp. 1607-1617 ◽  
Author(s):  
Ville Väisänen ◽  
Susann Eriksson ◽  
Kaisa K Ivaska ◽  
Hans Lilja ◽  
Martti Nurmi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Detection Limit ◽  
Solid Phase ◽  
Specific Antigen ◽  
Control Group ◽  
Serum Samples ◽  
Human Kallikrein 2 ◽  
Kallikrein 2 ◽  
Capture Antibody ◽  
Total Psa

Abstract Background: Free and total human kallikrein 2 (hK2) might improve the discrimination between prostate cancer and benign prostatic hyperplasia. Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific antigen (PSA); therefore, an hK2 assay must have a low detection limit and good specificity. Methods: PSA- and hK2-specific monoclonal antibodies were used in solid-phase, two-site immunofluorometric assays to detect free and total hK2. The total hK2 assay used PSA-specific antibodies to block nonspecific signal. The capture antibody of the free hK2 assay did not cross-react with PSA. To determine the hK2 concentrations in the male bloodstream, total hK2 was measured in a control group consisting of 426 noncharacterized serum samples. Free and total hK2 were measured in plasma from 103 patients with confirmed prostate cancer. Results: All 426 males in the control group had a total hK2 concentration above the detection limit of 0.0008 μg/L. The median total hK2 concentration was 0.022 μg/L (range, 0.0015–0.37 μg/L). hK2 concentrations were 0.1–58% of total PSA (median, 3.6%). hK2 concentrations were similar in men 41–50 and 51–60 years of age. The ratio of hK2 to PSA steadily decreased from 5–30% at PSA <1 μg/L to 1–2% at higher PSA concentrations. In 103 patients with prostate cancer, the median hK2 concentration in plasma was 0.079 μg/L (range, 0.0015–16.2 μg/L). The median free hK2 concentration was 0.070 (range, 0.005–12.2) μg/L. The proportion of free to total hK2 varied from 17% to 131% (mean, 85%). Conclusions: The wide variation in the free-to-total hK2 ratio suggests that hK2 in blood plasma is not consistently in the free, noncomplexed form in patients with prostate cancer. The new assay is sufficiently sensitive to be used to study the diagnostic accuracies of free and total hK2 for prostate cancer.

The value of (−7, −5)pro-prostate-specific antigen and human kallikrein-2 as serum markers for grading prostate cancer

2004 ◽  
Vol 93 (6) ◽  
pp. 720-724 ◽  
Author(s):  
C.H. Bangma ◽  
M.F. Wildhagen ◽  
G. Yurdakul ◽  
F.H. Schröder ◽  
B.G. Blijenberg
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Serum Markers ◽  
Human Kallikrein 2 ◽  
Kallikrein 2

scholarly journals Early prediction of prostate cancer biochemical recurrence and identification of disease persistence using PSA isoforms and human kallikrein-2

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 197-207
Author(s):  
Joana Do Carmo Silva ◽  
Stepan Vesely ◽  
Hana Luksanova ◽  
Richard Prusa ◽  
Marko Babjuk
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Specific Antigen ◽  
Early Postoperative Period ◽  
P Value ◽  
Single Marker ◽  
Human Kallikrein 2 ◽  
Kallikrein 2 ◽  
Disease Persistence

BACKGROUND: The role of isoforms of prostate specific antigen (PSA) and other kallikrein-related markers in early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is not well known and serum PSA is currently used in preoperative risk nomograms. OBJECTIVE: The aim of this research was to study pre- and early postoperative levels of important PSA isoforms and human kallikrein-2 to determine their ability to predict BCR and identify disease persistence (DP). METHODS: This study included 128 consecutive patients who underwent RP for clinically localized prostate cancer. PSA, fPSA, %fPSA, [–2]proPSA, PHI and hK2 were measured preoperatively, at 1 and 3 months after RP. We determined the ability of these markers to predict BCR and identify DP. RESULTS: The DP and BCR rate were 11.7%and 20.3%respectively and the median follow up was 64 months (range 3–76 months). Preoperatively, the independent predictors of BCR were PSA (p-value 0.029), [–2]proPSA (p-value 0.002) and PHI (p-value 0.0003). Post-RP, PSA was the single marker correlating with BCR, both at one (p-value 0.0047) and 3 months (p-value 0.0004). PSA, fPSA, [–2]proPSA and PHI significantly correlated to DP at 1 and 3 months post-RP (p-value <  0.05), although PSA had the most significant existing correlation (p-value <  0.0001). CONCLUSIONS: [–2]proPSA and PHI are preoperative predictors of BCR and DP that outperform the currently used serum PSA. At the early postoperative period there is no additional benefit of the other markers tested.

Molecular forms of prostate-specific antigen and human kallikrein 2 (hK2) in urine are not clinically useful for early detection and staging of prostate cancer

Urology ◽  
1997 ◽  
Vol 50 (5) ◽  
pp. 715-721 ◽  
Author(s):  
Jürgen Pannek ◽  
Harry G. Rittenhouse ◽  
Cindy L. Evans ◽  
Judith A. Finlay ◽  
Debra J. Bruzek ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Molecular Forms ◽  
Human Kallikrein 2 ◽  
Kallikrein 2

Serum Human Glandular Kallikrein-2 Protease Levels Predict the Presence of Prostate Cancer Among Men With Elevated Prostate-Specific Antigen

2000 ◽  
Vol 18 (5) ◽  
pp. 1036-1036 ◽  
Author(s):  
Robert K. Nam ◽  
Eleftherios P. Diamandis ◽  
Ants Toi ◽  
John Trachtenberg ◽  
Angeliki Magklara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Detection ◽  
Prostate Biopsy ◽  
Odds Ratio ◽  
Specific Antigen ◽  
Prostate Cancer Detection ◽  
Free Psa ◽  
Glandular Kallikrein ◽  
Kallikrein 2 ◽  
Total Psa

PURPOSE: We hypothesize that serum human glandular kallikrein-2 (hK2) levels predict the presence of prostate cancer among men prescreened by prostate-specific antigen (PSA).PATIENTS AND METHODS: We conducted a cross-sectional study of 324 men who had no history of prostate cancer and who were referred for prostate biopsy. PSA and hK2 levels were measured using specific nonisotopic immunometric techniques. Cases were patients who were diagnosed with adenocarcinoma of the prostate from biopsy, and controls were patients who had no evidence of cancer from biopsy. The odds ratio for detection of prostate cancer was determined for hK2 measurements, controlling for age, total-PSA level, digital rectal examination, and symptoms of urinary obstruction.RESULTS: Of 324 men, 159 (49.1%) had cancer. Mean hK2 levels and hK2:free-PSA ratios were significantly higher in cases than in controls (1.18 v 0.53 ng/mL, respectively, for hK2, P = .0001; 1.17 v 0.62 for hK2:free-PSA ratio, P = .0001). The crude odds ratio for prostate cancer detection for patients in the highest quartile of hK2 level was 5.83 (95% confidence interval [CI], 2.8 to 12.1; P = .0001) compared with patients in the lowest quartile. The adjusted odds ratio was 6.72 (95% CI, 2.9 to 15.6; P = .0001). Similarly, the crude and adjusted odds ratios for prostate cancer detection using the hK2:free-PSA ratio were 7.36 (95% CI, 3.6 to 15.1; P = .0001) and 8.06 (95% CI, 3.7 to 17.4; P = .0001), respectively. These odds ratios were higher than that observed for prostate cancer detection by total-PSA level (2.73; P = .03).CONCLUSION: Among men prescreened with PSA for prostate cancer, patients with high hK2 measurements have a five- to eight-fold increase in risk for prostate cancer, adjusting for PSA level and other established risk factors. hK2 measurements may be a useful adjunct to PSA in improving patient selection for prostate biopsy.

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