Prostate cancer is the second leading cause of cancer death in men. Almost 98% of prostate cancer cases are of glandular origin. The Gleason index is the most common for classifying prostate cancer.
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The beginning of the tumor process is usually asymptomatic, because it begins on the periphery, in the tissue somewhat distant from the urethra. Once the urethra and bladder neck are involved, obstructive symptoms develop, which include a reduction or cessation of urine flow. As the tumor progresses, patients often report hematospermia, a decrease in ejaculation (sperm release) - due to secondary obstruction (clogging) of the sperm-releasing duct. Erectile dysfunction may also develop due to local damage to neurovascular plexuses.
Bone pain usually characterizes the stage of development of metastases. Prostate cancer is characterized by osteoblastic metastases in bones in 95% of cases. In the process, as a result of secondary involvement of the bone marrow, anemia is often observed, as well as swelling of the lower parts of the body - which is caused by the obstruction of the lymphatic system.
Over the past few decades, the number of patients with symptoms of prostate cancer has decreased compared to diagnosed cases, which is explained by screening for prostate tumor markers.
Diagnostic and prognostic markers
The discovery of prostate-specific antigen in the 20s and its widespread introduction in the 70s and 80s simplified prostate cancer screening and monitoring of diagnosed cases. Biomarkers are evaluated by their positive predictive value (probability that a positive test indicates the presence of disease) and negative predictive value (probability that a negative test indicates the absence of disease) values, which determine the specificity and sensitivity of the biomarker.
Prostate-specific antigen (PSA)
The psa gene is a member of the kallikrein gene family on chromosome 19. Prostate-specific antigen functions as a serine protease (enzyme), which is synthesized in the epithelial cells of the prostate lumen. Its main function is to liquefy ejaculate. A large part of PSA circulating in the serum is related to protease inhibitor proteins (A1-antichymotrypsin, A2-macroglobulin). Processes such as inflammation, hyperplasia or neoplasia of the prostate tissue disrupt its natural barrier and lead to an increase in circulating PSA concentration in the serum.
The synthesis of prostate-specific antigen is androgen-dependent and its amount is influenced by age, race and the size of the present gland. There is an opinion that men with a high body mass index (BMI) have a lower concentration of PSA in plasma. Studies prove that the reason for this is not so much testosterone and dihydrotestosterone deficiency, as much as hemodilution (dilution of plasma). The larger the volume of plasma (according to body weight), the less PSA it contains. PSA is a widely used screening marker in the diagnostics of prostate cancer.
Free prostate-specific antigen
Free PSA is enzymatically inactive and constitutes 4-45% of total PSA. Men with prostate cancer have significantly lower free PSA levels than healthy men. A free PSA study is provided even in cases when a bulky process of the prostate is not fixed by rectal examination. Free PSA is informative in men with elevated total PSA and negative biopsy data.
PSA is also known as human kallikrein 3. However, there are other kallikreins that are actively used as markers for prostate cancer.
Kallikrein 2 is 80% amino acid sequence similar to PSA. A small amount is produced by prostate cells, and its synthesis increases in prostate cancer. In the early stages of cancer, expression is low and becomes aggressive as the disease progresses. Kallikrein-2, free PSA, total PSA together with clinical data are important indicators for evaluating the aggressiveness of the disease course.
Prostatic acid phosphatase (CARDBOARD)
Prostatic acid phosphatase was the first marker routinely used in the diagnostics and classification of prostate cancer. This enzyme hydrolyzes esters in an acidic environment and releases inorganic phosphates. It is also found in brain, lung, and liver tissue, although the highest concentration is in the present gland. Epithelial cells of the gland secrete acid phosphatase into the lumen of the gland. Studies have shown an increase in acid phosphatase in patients with metastatic prostate cancer. After the use of prostate-specific antigen for diagnostics, the diagnostic value of acid phosphatase decreased.
Interleukin-6 is involved in the regulation of many cellular processes, including bone turnover and immune activity. Immunohistochemical studies showed that interleukin-6 protein concentration was increased 18 times in prostate cancer tissue compared to healthy tissue. Plasma interleukin-6 concentration is markedly increased in metastatic prostate tumors.
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