Basic research supporting diagnostics
Principal investigator: Professor Kim Pettersson, Ph.D.
Staff
Project researchers
Saeid Alinezhad, M.Sc.
Md. Ferdhos Khan Liton, M.Sc.
Mari Peltola, M.Sc.
Riina-Minna Väänänen, M.Sc.
Research
The focus of research is concentrated on field of prostatic kallikreins but also searches for alternative marker candidates suitable for routine clinical use. A special interest is to determine the pathological potential of an early cancer using biopsy specimens or prostatic cells shedded into the bone marrow or the circulation. Quantitative real timePCR of mRNA for a panel of markers could conceivably serve as a molecular signature of the tumor aggressiveness, more specifically its capability to establish distant metastases to the bone. In this endeavor, methodological objectives join with the identification of novel biochemical indicators of improved prognostic and diagnostic utility.
Prostate cancer (PC) is the most frequent cancer of men in many industrialized countries, and a leading cause of cancer death. PC when diagnosed from clinical symptoms is frequently beyond cure and only eligible for hormonal treatments or expectant follow-up. Early detection (screening) of PC has therefore been suggested and extensive studies have been initiated with the aim to find out whether early detection followed by curative measures will have a positive effect on the life expectancy compared to conservative "watchful waiting" approaches.
Prostate specific antigen (PSA) is a sensitive PC marker as it is clearly increased up to 15 year prior to "surfacing" clinically. PSA is, however, increased also in benign prostatic disorders giving rise to a large number of false positive cases, which will be subjected to the definitive but invasive diagnostic procedure i.e. tissue biopsy.
Although biochemical detection of early PC by PSA is widely used there is a fear that many cancers of low pathological potential are also found and treated. It is presently widely that felt prostate cancer overdiagnosis has become a significant problem as opportunistic PSA screening has been more widely implemented. Unnecessary treatments represent a burden both for the patient (side effects) and for the whole health care system (consuming resources). Therefore biomarkers that would indicate tumor aggressiveness accurately enough to guide treatment decisions for the individual patient are urgently needed.
The MPC group at the Department of Biotechnology has since its start been involved in basic and applied research on the prostatic kallikreins (PSA and hK2) and its circulating forms. A major finding was that PSA a serine protease, occurs both in a free form and complexed to a serpine (ACT). This finding has lead to a significant improvement in prostate cancer diagnostics by measuring the free PSA in relation to total PSA. Today numerous commercial assays exist on the market to serve this common routine application.
The MPC group continues its research efforts in the field of prostatic kallikreins but also searches for alternative marker candidates suitable for routine clinical use. A special interest is to detemine the pathological potential of an early cancer using biopsy specimens or prostatic cells shedded into the bone marrow or the circulation. Quantitative RT-PCR of mRNA for a panel of markers could conceivably serve as a molecular signature of the tumor aggressiveness, more specifically its capability to establish distant metastases to the bone. In this endeavor, methodological objectives join with the identification of novel biochemical indicators of improved prognostic and diagnostic utility.
Clinical studies are being carried out in collaboration with a number of national and international clinical centres mainly using serum samples but also cell- and tissue preparations from clinically characterised patients with different prostatic disorders.
Financing of the MPC project has mainly been obtained from the Academy of Finland, Tekes, EU (P-Mark of the 6th framework; www.p-mark.org and PRO-NEST www.pro-nest.org) as well as through agreements with commercial national and international diagnostic companies. The research group consists of senior researchers, PhD students, graduate students and technical personnel.
Recent publications
Väänänen RM, Rissanen M, Kauko O, Junnila S, Väisänen V, Nurmi J, Alanen K, Nurmi M, Pettersson K. (2008)Quantitative real-time RT-PCR assay for PCA3. Clin Biochem. 41:103-108
Rissanen M, Helo P, Väänänen RM, Wahlroos V, Lilja H, Nurmi M, Pettersson K, Nurmi J. (2007) Novel homogenous time-resolved fluorometric RT-PCR assays for quantification of PSA and hK2 mRNAs in blood. Clin Biochem. 40:111-118
Väisänen V, Peltola MT, Lilja H, Nurmi M, Pettersson K. (2007) Intact free prostate-specific antigen and free and total human glandular kallikrein 2. Elimination of assay interference by enzymatic digestion of antibodies to F(ab')2 fragments. Anal Chem. 78:7809-7815