Tissue prostatic specific antigen (T-PSA) : A way to predict and understand the development of prostate cancer

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Clinical Sciences

Sammanfattning: Prostate cancer (CaP) is the most prevalent malignancy among men in Sweden. One major problem associated with CaP is the choice of treatment since the disease may develop very differently from patient to patient. Many efforts have focused on the development of markers for prognosis and monitoring treatment affecting the endocrine system of CaP. In this respect prostate specific antigen in serum (S-PSA) is currently the most commonly used marker. We have evaluated PSA levels measured in fine needle aspiration biopsies from tumor tissue (tissue PSA, T-PSA) for prognosis of CaP outcome and its use as a tool for understanding the development of the disease. T-PSA and S-PSA values in metastasis-free (MO) patients were inversely correlated, indicating that S-PSA levels reflect the degree of leakage of PSA into the blood stream rather than the production of PSA in the tumor. T-PSA measurement at the time of diagnosis was more effective than cytological grade, tumor stage, DNA ploidy and total and free serum PSA as a predictor for the outcome of therapy. Moreover, the change in T-PSA between 12 and 0 months of treatment was an even better predictor in this respect. In patients who did not respond to treatment initial T-PSA values were low but increased dramatically during treatment. Our patients were treated surgically with bilateral orchidectomy / GnRH analogues (ZoladexTm) or with parenteral depot estrogens (EstradurinTm). In MO patients who responded to treatment, T-PSA values were significantly higher in estrogen treated patients than in patients treated by orchidectomy / with GnRH analogues, indicating a stimulatory action of estrogens on PSA synthesis in vivo. Estrogens are used in the treatment of CaP, but may also have a role in the etiology of the disease. We therefore studied the effects of estrogens on vasoactive factors of possible importance in CaP, using hormone sensitive (LNCaP-FGC) and hormone resistant (LNCaP-r) cell line. We found that estrogens stimulated mRNA expression of the vasoactive factor, ecNOS but suppressed mRNA expression of ET- 1. Estrogens may therefore influence CaP through alteration of these factors. Our findings demonstrate that the levels of T-PSA can be directly related to the prognosis of prostate cancer. In the future, protein characterization of the tumors may improve our ability to predict the outcome for patients with this disease.

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