Abstract

Introduction: New methods for early diagnosis and treatment of prostate cancer are continuously being developed. The large majority of prostate cancers and also benign prostate hyperplasi (BPH) are detected, via prostate- specific antigen (PSA) screening. However, management policies for patients with PSA levels in the so called “gray zone”, i.e. between 2.5-10ng/ml are not clear. PSA density, PSA velocity, Free/Total PSA, complex PSA and age adjusted PSA levels have been suggested as adjuvant markers for treatment decisions for these patients. Nitric oxide (NO) was first introduced by Furcgatt and Zawadzki in 1980 as a vasodilatator which is secreted by endothelium. NO produced by the enzyme nitric oxide synthase during the transformation of L-arginin to L-sitrulin. NO has many functions in the body; smooth muscle relaxation, inhibition of aggregation of thrombocites, acting as a neurotransmitter in the brain, as well as having a role in inflammation and immunology. The inducible NOS (i-nos) isn’t calcium dependent-analysis particularly found in thrombocytes and the liver. Its release is stimulated by bacterial endotoxins and cytokines. In this prospective study our objective was to search for a probable correlation between various PSA levels and NO levels in BPH, prostate cancer and other urinary tract malignancies.

Materials and Methods: Between August 2001 and February 2002, 90 male patients with LUTS and 15 healthy volunteers (age 70±15) were included in this study. These patients didn’t have acute infection. Those using nitrates were excluded. Urinary obstruction was diagnosed by uroflowmetry and 90 patients were introduced to the study prospectively. Patients were categorized in 7 groups as follows; control, BPH (2 groups; first PSA 2.5-10 and second 10 ng/ml and higher), P Ca (3 groups; first, PSA 2.5-10, second 10 ng/ml and higher, and thirdly; patients who underwent radical prostatectomy), and other urinary tract malignancies. Each group consisted of 15 cases and each case had histopathologic correlation. All the serum samples were frozen et -70°C before they were used. Serum total PSA levels were identified using electrochemiluminesance (ECL) method with roche 2010 system. Serum NO levels were measured using the reduction of nitrate to nitrite which can be measured after a colorimetric reaction with Griess reagent.

Results: NO value for the control group was 4.55±1.57 uM. PSA values for the first BPH group was 6.44±2.84 uM and for the second BPH group it was 6.47±2.41 uM. PSA values for 3 P Ca groups were 8.88±5,34 ulvl, 7.74±3.49 uM, 5.56±1.81 uM respectively. NO levels were statistically significantly high in BPH, P Ca and other urinary tract malignancies (p<0.01). NO increased in the BPH group did not correlate with PSA. NO increase was higher in P Ca and other urinary tract malignancies when compared to BPH. NO increase in P Ca cases with PSA levels 2.5-10 ng/ml was statistically significantly higher than those with PSA levels 10 ng/ml and higher. There was a statistically significant decrease in NO levels in patients who underwent radical cystoprostatectomy by the post operative third month (PSA: 0.01±0.01 ng/ml). There was no statistically significant difference with in the control group.

Conclusion: Our results show that NO levels increase both in BPH and other urinary tract malignancies; the increase is higher in malignancies. Significant decrease in NO levels in patients that had undergone radical prostatectomy suggests that there might be a correlation between NO levels and carcinoma.