Human glandular kallikrein 2 (hK2) in prostate cancer: Clinical and Methodological studies

Detta är en avhandling från Dept. of Laboratory Medicine. Div. of Clinical Chemistry, Malmö University Hospital, SE 205 02 Malmö , Sweden

Sammanfattning: Human glandular kallikrein 2 (hK2) is a predominantly prostate produced protein with many similarities to prostate-specific antigen (PSA). Just like for PSA elevated levels of hK2 can be found in men with protate cancer. We created an assay where hK2 in serum could reliably and with negligible cross-reactivity with PSA, be measured down to 0.030 ng/mL. The assay measured free hK2 and hK2 complexed to ACT with a –6% bias to free hK2. Gel-filtration of serum with elevated hK2 concentrations showed that the predominant form found in serum was free hK2. We then studied the utility of hK2 measurements in the differentiation of men with benign prostatic hyperplasia (BPH) from men with prostate cancer (PCa). The addition of hK2 to measurements to free and total PSA improved the differentiation of men with BPH from men with clinically localized prostate cancer. In order to study weather hK2 was useful in the clinical staging of prostate cancer, we measured hK2 in preoperative sera derived from prostatectomized men. The levels of hK2 was found to be significantly different in men with organ confined prostate cancer compared to men with nonorgan confined prostate cancer. High concentrations of hK2 makes a nonorgan confined prostate cancer likely. The utility of hK2 measurements were also studied in a population of men participating in the Göteborg screening study for prostate cancer. The men studied were all biopsied due to PSA concentrations of 3.0 ng/mL of higher. We could demonstrate that hK2 used in combination with free and total PSA (hK2 x total PSA / free PSA) improved the differentiation of men with and without prostate cancer. By this combination we saw a significant improvement in sensitivity at high levels of specificity compared to by use of percent free PSA or total PSA.Two years after the first screening, the same cohort of men were called for a new serum PSA test. Again, we studied the men biopsied due to elevated PSA and found that hK2 in combination with free and total PSA improved the separation of men with and without cancer, however less significant than in the first round of screening. We found that hK2 increased almost two-fold, and significantly higher, in men with cancer over a two year period compared to in men without cancer.

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