Prostate Specific Antigen Pdf Free
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Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the KLK3 gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland.
PSA can also be found at low levels in other body fluids, such as urine and breast milk, thus setting a high minimum threshold of interpretation to rule out false positive results and conclusively state that semen is present. While traditional tests such as crossover electrophoresis have a sufficiently low sensitivity to detect only seminal PSA, newer diagnostics tests developed from clinical prostate cancer screening methods have lowered the threshold of detection down to 4 ng/mL. This level of antigen has been shown to be present in the peripheral blood of males with prostate cancer, and rarely in female urine samples and breast milk.
PSA is produced in the epithelial cells of the prostate, and can be demonstrated in biopsy samples or other histological specimens using immunohistochemistry. Disruption of this epithelium, for example in inflammation or benign prostatic hyperplasia, may lead to some diffusion of the antigen into the tissue around the epithelium, and is the cause of elevated blood levels of PSA in these conditions.
More significantly, PSA remains present in prostate cells after they become malignant. Prostate cancer cells generally have variable or weak staining for PSA, due to the disruption of their normal functioning. Thus, individual prostate cancer cells produce less PSA than healthy cells; the raised serum levels in prostate cancer patients is due to the greatly increased number of such cells, not their individual activity. In most cases of prostate cancer, though, the cells remain positive for the antigen, which can then be used to identify metastasis. Since some high-grade prostate cancers may be entirely negative for PSA, however, histological analysis to identify such cases usually uses PSA in combination with other antibodies, such as prostatic acid phosphatase and CD57.
Prostate-specific antigen (PSA, also known as kallikrein III, seminin, semenogelase, γ-seminoprotein and P-30 antigen) is a 34-kD glycoprotein produced almost exclusively by the prostate gland. It is a serine protease (EC 22.214.171.124) enzyme, the gene of which is located on the 19th chromosome (19q13) in humans.
The discovery of prostate-specific antigen (PSA) is beset with controversy; as PSA is present in prostatic tissue and semen, it was independently discovered and given different names, thus adding to the controversy.
In 1978, Sensabaugh identified semen-specific protein p30, but proved that it was similar to E1 protein, and that prostate was the source. In 1979, Wang purified a tissue-specific antigen from the prostate ('prostate antigen').
Despite earlier findings, recent research suggests that the rate of increase of PSA (e.g. >0.35 ng/mL/yr, the 'PSA velocity') is not a more specific marker for prostate cancer than the serum level of PSA.
Most PSA in the blood is bound to serum proteins. A small amount is not protein-bound and is called 'free PSA'. In men with prostate cancer, the ratio of free (unbound) PSA to total PSA is decreased. The risk of cancer increases if the free to total ratio is less than 25%. (See graph at right.) The lower the ratio is, the greater the probability of prostate cancer. Measuring the ratio of free to total PSA appears to be particularly promising for eliminating unnecessary biopsies in men with PSA levels between 4 and 10 ng/mL. However, both total and free PSA increase immediately after ejaculation, returning slowly to baseline levels within 24 hours.
The PSA test in 1994 failed to differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the commercial assay kits for PSA did not provide correct PSA values. Thus with the introduction of the ratio of free-to-total PSA, the reliability of the test has improved. Measuring the activity of the enzyme could add to the ratio of free-to-total PSA and further improve the diagnostic value of test. Proteolytically active PSA has been shown to have an anti-angiogenic effect  and certain inactive subforms may be associated with prostate cancer, as shown by MAb 5D3D11, an antibody able to detect forms abundantly represented in sera from cancer patients.The presence of inactive proenzyme forms of PSA is another potential indicator of disease.
PSA exists in serum in the free (unbound) form and in a complex with alpha 1-antichymotrypsin; research has been conducted to see if measurements of complexed PSA are more specific and sensitive biomarkers for prostate cancer than other approaches.
It is now clear that the term prostate-specific antigen is a misnomer: it is an antigen but is not specific to the prostate. Although present in large amounts in prostatic tissue and semen, it has been detected in other body fluids and tissues.
Prostate-specific antigen has been shown to interact with protein C inhibitor.Prostate-specific antigen interacts with and activates the vascular endothelial growth factors VEGF-C and VEGF-D, which are involved in tumor angiogenesis and in the lymphatic metastasis of tumors.
The early detection of bone metastases is very important in prostate cancer follow-up. This study aimed to compare conventional tumor markers, namely free prostate-specific antigen (free PSA), total prostate-specific antigen (total PSA), free PSA/total PSA ratio, alkaline phosphatase (ALP) values, Gleason scores and 99 m Tc-MDP bone scintigraphy findings in the prediction of bone metastases in prostate cancer.
In total, 175 patients with prostate cancer who underwent whole-body bone scintigraphy were included in the study. All selected scintigraphic studies were reprocessed. Free PSA, total PSA, free PSA/total PSA ratio, alkaline phosphatase (ALP) values and Gleason scores of patients were recorded.
According to the results of our study; the free PSA, total PSA, free PSA/total PSA ratio and Gleason score values were not considered as a reliable parameter in the prostate cancer cases follow-up for bone metastasis development. Only ALP had a diagnostic value and ALP cutoff value was 76.50 IU / L with 80% sensitivity and 82.1% specificity in predicting bone metastases in prostate cancer.
Prostate cancer is the second-most commonly diagnosed cancer among men worldwide after lung cancer and ranks fifth for cancer-related mortality rates. Definitive prostate cancer diagnoses are made by biopsy. Patient selection for biopsy is important to prevent unnecessary diagnosis/treatment. The most important marker used to decide which patients should be considered for biopsy is the serum prostate-specific antigen (PSA) value [1,2,3]. However, PSA, which is a glycoprotein produced by the prostate tissue, increases not only in the case of prostate cancer but also in the case of a variety of benign diseases such as benign prostate hypertrophy (BPH), prostatitis and urinary infections . In addition, the specificity and positive predictive value of PSA, as a commonly used marker in prostate cancer screening, is low and an exact cutoff value has not yet been defined . In clinical routine, the differentiation of BPH and prostate cancer in patients with PSA levels between 4.0 ng/mL and 10.0 ng/mL is difficult [6, 7].
Due to these limitations, the use of different forms or kinetics of PSA has been recommended. However, recent studies have revealed that no biomarker alone is sufficient in diagnosis and a multivariable diagnostic approach is more eligible [5, 8, 9]. Nevertheless, due to some disadvantages of these markers, the free prostate-specific antigen/total prostate-specific antigen (free PSA/total PSA) ratio has become the most frequently used value in clinical practice [9, 10]. Recently, it has been reported in the literature that the free PSA/total PSA ratio is more significant than PSA alone in differentiating prostate cancer and BPH in patients with serum total PSA levels between 4.0 and 10.0 ng/mL [11, 12].
Prostate cancer mainly causes osteoblastic bone metastasis. The number of metastases in the bones is important in predicting the response to therapy and is generally associated with decreased survival rates . Therefore, the early diagnosis of bone metastasis is substantial. Bone scintigraphy is frequently used as a non-invasive, inexpensive and easily accessible imaging method to detect bone metastasis. In addition, bone scintigraphy has been recommended in major urology guidelines as an imaging method for bone metastasis screening in medium-to-high risk patient groups and symptomatic patients. PSA values, Gleason Scores and the clinical stage of the lesion have been known to affect the success rate of this method [14, 15]. This study aimed to investigate the prognostic significance of the free PSA/total PSA ratio, which has been recently reported to be a more sensitive marker in detecting bone metastasis in prostate cancer.
Bone scintigraphy images of three prostate cancer patients at different stages. a: An example patient without bone metastases; free PSA: 2.53 ng/ml, total PSA:17.54 ng/ml, free/total PSA ratio: 0.144, ALP: 43 U/L, b: An example patient with numerous metastases; free PSA: 3.11 ng/ml, total PSA:18.30 ng/ml, free/total PSA ratio: 0.169, ALP: 114 U/L. C: An example patient with multiple metastases; free PSA: 12.90 ng/ml, total PSA:121.20 ng/ml, free/total PSA ratio: 0.106, ALP: 109 U/L
On the other hand, various studies have reported that the free PSA/total PSA ratio is not as significant as expected. For example, Agnihotri S et al. concluded that the value of free PSA/total PSA in symptomatic males and found a very limited value to improve specificity of total PSA . Moreover, Huyghe E et al. claimed that the calculation of the free PSA/ total PSA ratio did not appear to provide any decisional criteria in favor of radical prostatectomy . 2b1af7f3a8