Intact and internally cleaved free prostate-specific antigen in patients with prostate cancer with different pathologic stages and grades.

OBJECTIVES: To measure the concentration levels of free prostate-specific antigen (PSA) isoforms in patients with prostate cancer selected for curative treatment using radical prostatectomy and to study the association between the isoforms and the pathologic cancer stage and grade. METHODS: Preoperative plasma samples were obtained from 309 consecutive patients scheduled to undergo radical prostatectomy at Turku University Hospital. The pathologic TNM stage, Gleason score, and World Health Organization grade of the tumors were recorded. The total, free, and intact PSA (tPSA, fPSA, and fPSA-I, respectively) concentrations of the archived samples were measured with in-house immunoassays, and the nicked PSA (fPSA-N) concentrations (fPSA minus fPSA-I) and ratios of different PSA forms were calculated. These were compared with the prostate cancer stage, Gleason score, and World Health Organization grade. RESULTS: The median fPSA-I and fPSA-N concentrations in the patients with prostate cancer was 0.42 and 0.28 ng/mL, constituting an average of 60% and 40% of fPSA, respectively. The nicked/total PSA and free/total PSA ratios had the strongest negative correlations with a higher pathologic stage, Gleason score, and World Health Organization grade (Spearman rho -0.205 to -0.262, P < .05). Within a patient subgroup with tPSA <10 ng/mL, fPSA-N as a single marker had a negative correlation with a higher Gleason score (rho -0.160, P = .021). CONCLUSIONS: Lower proportions of fPSA-I and fPSA-N to total PSA were associated with a more advanced cancer stage and grade. A long-term follow-up study and a comparison with currently used clinical methods are needed to evaluate the usefulness of the analytes as prognostic markers for cancer aggressiveness in individual patients.

Free and total human glandular kallikrein 2 in patients with prostate cancer.

OBJECTIVES: The use of prostate-specific antigen (PSA, hK3) results in the overdiagnosis and overtreatment of prostate cancer. Markers are needed that could identify aggressive, fast-growing tumors and help decide which patients would benefit most from aggressive treatment. Human glandular kallikrein 2 (hK2) could be such a marker. The aim of this study was to test how PSA and hK2 could predict the pathologic stage and grade in a set of patients with clinically organ-confined disease. METHODS: Heparin plasma was collected from 188 patients who had undergone radical prostatectomy at the Turku University Central Hospital. Total and free PSA, as well as total and free hK2, were measured and the results compared with the pathologic TNM stage, tumor World Health Organization grade, and Gleason score. RESULTS: Free and total hK2 performed similarly to PSA in their ability to separate groups of patients with different stages or grades. Concentrations of both kallikreins were significantly different in patients with World Health Organization grade 1 cancer compared with grade 2. Neither marker could separate patients with different Gleason scores. Although PSA concentrations increased most between patients with Stage pT2b and those with pT3a, the increase in hK2 was most pronounced between those with Stage pT3a and those with pT3b. CONCLUSIONS: Although hK2 could not predict the cancer stage or grade better than PSA, changes in the hK2 and PSA concentrations occurred at different points in cancer progression. hK2 may have a role in the prognosis of prostate cancer, but additional studies with longer follow-up are required to determine whether hK2 can help when selecting treatment options.

Segregation of the ND4/11778 and the ND1/3460 mutations in four heteroplasmic LHON families.

Leber hereditary optic neuropathy (LHON) is an ocular disease associated with mutations in the mitochondrial DNA (mtDNA). The level of heteroplasmy in the mtDNA mutations ND4/11778 and ND1/3460 was followed over a period of 4-12 years in blood samples taken from nine members of four heteroplasmic LHON families. In addition, hair follicle and urinary tract epithelium samples of one individual were studied. The quantification of heteroplasmy was performed using the solid-phase minisequencing method. Only minor and random shifts in the heteroplasmy levels were observed over time, but there were no systematic changes towards an increasing or decreasing proportion of either LHON mutant in the individuals. This indicates that there is no selection for either mtDNA genotype but the segregation of the wild-type mtDNAs and those carrying LHON mutations is a stochastic process governed by random genetic drift. In this respect, LHON mutations seem to behave like neutral polymorphisms.