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Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glyco ...
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
encoded in humans by the ''KLK3''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. PSA is a member of the
kallikrein Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein (encoded by '' KLKB1 gene'') has no known paralogue, while tissue kallikrein-related peptidases (''KLKs'') encode a ...
-related
peptidase A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...
family and is secreted by the
epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...
of the
prostate The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and phys ...
gland. PSA is produced for the
ejaculate Ejaculation is the discharge of semen (the ''ejaculate''; normally containing sperm) from the male reproductory tract as a result of an orgasm. It is the final stage and natural objective of male sexual stimulation, and an essential componen ...
, where it liquefies
semen Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Sem ...
in the seminal coagulum and allows
sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, ...
to swim freely. It is also believed to be instrumental in dissolving
cervical mucus The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
, allowing the entry of sperm into the
uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
. PSA is present in small quantities in the
serum Serum may refer to: * Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid *Truth serum, a drug that is likely to mak ...
of men with healthy prostates, but is often elevated in the presence of
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that su ...
or other prostate disorders. PSA is not uniquely an indicator of prostate cancer, but may also detect
prostatitis Prostatitis is an umbrella term for a variety of medical conditions that incorporate bacterial and non-bacterial origin illnesses in the pelvic region. In contrast with the plain meaning of the word (which means "inflammation of the prostate"), the ...
or
benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...
.


Medical uses


Prostate cancer


Screening

Clinical practice guideline Clinical may refer to: Healthcare * Of or about a clinic, a healthcare facility * Of or about the practice of medicine Other uses * ''Clinical'' (film), a 2017 American horror thriller See also * * * Clinical chemistry, the analysis of bodily flu ...
s for prostate cancer
screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), ...
vary and are controversial, in part due to uncertainty as to whether the benefits of screening ultimately outweigh the risks of
overdiagnosis Overdiagnosis is the diagnosis of disease that will never cause symptoms or death during a patient's ordinarily expected lifetime and thus presents no practical threat regardless of being pathologic. Overdiagnosis is a side effect of screening fo ...
and overtreatment. In the United States, the
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) has approved the PSA test for annual screening of prostate cancer in men of age 50 and older. The patient is required to be informed of the risks and benefits of PSA testing prior to performing the test. In the United Kingdom, the
National Health Service The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...
does not mandate, nor advise for PSA test, but allows patients to decide based on their doctor's advice. The National Health Service does not offer general PSA screening, for similar reasons. PSA levels between 4 and 10ng/mL (nanograms per milliliter) are considered to be suspicious and consideration should be given to confirming the abnormal PSA with a repeat test. If indicated,
prostate biopsy Prostate biopsy is a procedure in which small hollow needle-core samples are removed from a man's prostate gland to be examined for the presence of prostate cancer. It is typically performed when the result from a PSA blood test is high. It may ...
is performed to obtain a tissue sample for histopathological analysis. While PSA testing may help 1 in 1,000 avoid death due to prostate cancer, 4 to 5 in 1,000 would die from prostate cancer after 10 years even with screening. This means that PSA screening may reduce mortality from prostate cancer by up to 25%. Expected harms include anxiety for 100 – 120 receiving false positives, biopsy pain, and other complications from biopsy for false positive tests. Use of PSA screening tests is also controversial due to questionable test accuracy. The screening can present abnormal results even when a man does not have cancer (known as a false-positive result), or normal results even when a man does have cancer (known as a false-negative result). False-positive test results can cause confusion and anxiety in men, and can lead to unnecessary prostate
biopsies A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disea ...
, a procedure which causes risk of pain, infection, and
hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, v ...
. False-negative results can give men a false sense of security even though they may actually have cancer. Of those found to have prostate cancer, overtreatment is common because most cases of prostate cancer are not expected to cause any symptoms due to low rate of growth of the prostate tumor. Therefore, many will experience the side effects of treatment, such as for every 1000 men screened, 29 will experience erectile dysfunction, 18 will develop urinary incontinence, two will have serious cardiovascular events, one will develop pulmonary embolus or deep venous thrombosis, and one perioperative death. Since the expected harms relative to risk of death are perceived by patients as minimal, men found to have prostate cancer usually (up to 90% of cases) elect to receive treatment.


Risk stratification and staging

Men with prostate cancer may be characterized as low-, intermediate-, or high-risk for having/developing metastatic disease or dying of prostate cancer. PSA level is one of three variables on which the risk-stratification is based; the others are the grade of prostate cancer (
Gleason grading system The Gleason grading system is used to help evaluate the prognosis of men with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts pr ...
) and the stage of cancer based on physical examination and imaging studies. D'Amico Criteria for each risk category are as follows: :Low-risk: PSA < 10, Gleason score ≤ 6, AND clinical stage ≤ T2a :Intermediate-risk: PSA 10-20, Gleason score 7, OR clinical stage T2b/c :High-risk: PSA > 20, Gleason score ≥ 8, OR clinical stage ≥ T3 Given the relative simplicity of the 1998 D'Amico criteria (above), other predictive models of risk stratification based on
mathematical probability Probability theory is the branch of mathematics concerned with probability. Although there are several different probability interpretations, probability theory treats the concept in a rigorous mathematical manner by expressing it through a set o ...
constructs exist or have been proposed to allow for better matching of treatment decisions with disease features. Studies are being conducted into the incorporation of multiparametric MRI imaging results into
nomogram A nomogram (from Greek , "law" and , "line"), also called a nomograph, alignment chart, or abac, is a graphical calculating device, a two-dimensional diagram designed to allow the approximate graphical computation of a mathematical function ...
s that rely on PSA, Gleason grade and tumor stage.


Post-treatment monitoring

PSA levels are monitored periodically (e.g., every 6–36 months) after treatment for prostate cancer – more frequently in patients with high-risk disease, less frequently in patients with lower-risk disease. If surgical therapy (i.e., radical prostatectomy) is successful at removing all prostate tissue (and prostate cancer), PSA becomes undetectable within a few weeks. A subsequent rise in PSA level above 0.2ng/mL L is generally regarded as evidence of recurrent prostate cancer after a radical prostatectomy; less commonly, it may simply indicate residual benign prostate tissue. Following radiation therapy of any type for prostate cancer, some PSA levels might be detected, even when the treatment ultimately proves to be successful. This makes it more difficult to interpret the relationship between PSA levels and recurrence/persistence of prostate cancer after radiation therapy. PSA levels may continue to decrease for several years after radiation therapy. The lowest level is referred to as the PSA nadir. A subsequent increase in PSA levels by 2.0ng/mL above the nadir is the currently accepted definition of prostate cancer recurrence after radiation therapy. If recurrent prostate cancer is detected by a rise in PSA levels after curative treatment, it is referred to as a "
biochemical recurrence Biochemical recurrence is a rise in the blood level of prostate-specific antigen (PSA) in prostate cancer patients after treatment with surgery or radiation. Biochemical recurrence may occur in patients who do not have symptoms. It may mean that t ...
". The likelihood of developing recurrent prostate cancer after curative treatment is related to the pre-operative variables described in the preceding section (PSA level and grade/stage of cancer). Low-risk cancers are the least likely to recur, but they are also the least likely to have required treatment in the first place.


Histology

PSA is produced in the
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...
cells of the prostate, and can be demonstrated in biopsy samples or other
histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
specimens using
immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to ant ...
. Disruption of this epithelium, for example in inflammation or
benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...
, 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. However, in most cases of prostate cancer, the cells remain positive for the antigen, which can therefore be used to identify
metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, the ...
. 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 PSAP and
CD57 3-beta-glucuronosyltransferase 1 (B3GAT1) is an enzyme that in humans is encoded by the ''B3GAT1'' gene, whose enzymatic activity creates the CD57 epitope on other cell surface proteins. In immunology, the CD57 antigen (CD stands for cluster of ...
.


Forensic identification of semen

PSA was first identified by researchers attempting to find a substance in seminal fluid that would aid in the investigation of rape cases. PSA is now used to indicate the presence of
semen Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Sem ...
in forensic
serology Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mic ...
. The semen of adult males has PSA levels far in excess of those found in other tissues; therefore, a high level of PSA found in a sample is an indicator that semen may be present. Because PSA is a
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
that is expressed independently of
spermatozoa A spermatozoon (; also spelled spermatozoön; ; ) is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote. (A zygote is a single cell, with a complete set of chromos ...
, it remains useful in identifying semen from vasectomized and
azoospermic Azoospermia is the medical condition of a man whose semen contains no sperm. It is associated with male infertility, but many forms are amenable to medical treatment. In humans, azoospermia affects about 1% of the male population and may be seen ...
males. 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 A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resul ...
results and conclusively state that semen is present. While traditional tests such as crossover
electrophoresis Electrophoresis, from Ancient Greek ἤλεκτρον (ḗlektron, "amber") and φόρησις (phórēsis, "the act of bearing"), is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric fi ...
have a sufficiently low sensitivity to detect only seminal PSA, newer diagnostics tests developed from clinical
prostate cancer screening Prostate cancer screening is the screening process used to detect undiagnosed prostate cancer in men without signs or symptoms. When abnormal prostate tissue or cancer is found early, it may be easier to treat and cure, but it is unclear if early ...
methods have lowered the threshold of detection down to 4ng/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. No studies have been performed to assess the PSA levels in the tissues and secretions of pre-pubescent children. Therefore, the presence of PSA from a high sensitivity (4ng/mL) test cannot conclusively identify the presence of semen, so care must be taken with the interpretation of such results.


Mechanism of action

The physiological function of KLK3 is the dissolution of the coagulum, the sperm entrapping gel composed of
semenogelin Semenogelin is a protein that is involved in the formation of a gel matrix that encases ejaculated spermatozoa, preventing capacitation. It blocks capacitation mainly via inhibition of reactive oxygen species In chemistry, reactive oxygen species ...
s and
fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as coll ...
. Its proteolytic action is effective in liquefying the coagulum so that the sperm can be liberated. The activity of PSA is well regulated. In the prostate, it is present as an inactive pro-form which is activated through the action of
KLK2 Kallikrein-2 is a protein that in humans is encoded by the ''KLK2'' gene, and is particularly associated with prostatic tissue. References Further reading * * * * * * * * * * * * * * * * * * * External links * The MEROPS MEROPS is an onli ...
, another kallikrein-related peptidase. In the prostate, zinc ion concentrations are ten times higher than in other bodily fluids. Zinc ions have a strong inhibitory effect on the activity of PSA and on that of KLK2, so that PSA is totally inactive. Further regulation is achieved through pH variations. Although its activity is increased by higher pH, the inhibitory effect of zinc also increases. The pH of semen is slightly alkaline and the concentrations of zinc are high. On ejaculation, semen is exposed to the acidic pH of the
vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
, due to the presence of
lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as nat ...
. In fertile couples, the final vaginal pH after coitus approaches the 6-7 levels, which coincides well with reduced zinc inhibition of PSA. At these pH levels, the reduced PSA activity is countered by a decrease in zinc inhibition. Thus, the coagulum is slowly liquefied, releasing the sperm in a well-regulated manner.


Biochemistry

Prostate-specific antigen (PSA, also known as kallikrein III, seminin, semenogelase, γ-seminoprotein and P-30 antigen) is a 34- kD
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glyco ...
produced almost exclusively by the
prostate gland The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and physi ...
. It is a
serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Seri ...
()
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
, the
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
of which is located on the 19th
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
(19q13) in humans.


History

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. Flocks was the first to experiment with antigens in the prostate and 10 years later Ablin reported the presence of precipitation antigens in the prostate. In 1971, Mitsuwo Hara characterized a unique protein in the semen fluid, gamma-seminoprotein. Li and Beling, in 1973, isolated a protein, E1, from human semen in an attempt to find a novel method to achieve fertility control. 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'). PSA was first measured quantitatively in the blood by Papsidero in 1980, and Stamey carried out the initial work on the clinical use of PSA as a marker of prostate cancer.


Serum levels

PSA is normally present in the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
at very low levels. The
reference range In medicine and health-related fields, a reference range or reference interval is the range or the interval of values that is deemed normal for a physiological measurement in healthy persons (for example, the amount of creatinine in the blood, o ...
of less than 4ng/mL for the first commercial PSA test, the Hybritech Tandem-R PSA test released in February 1986, was based on a study that found 99% of 472 apparently healthy men had a total PSA level below 4ng/mL. * * * * * * * Increased levels of PSA may suggest the presence of prostate cancer. However, prostate cancer can also be present in the complete absence of an elevated PSA level, in which case the test result would be a
false negative A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resul ...
.
Obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
has been reported to reduce serum PSA levels. Delayed early detection may partially explain worse outcomes in obese men with early prostate cancer. After treatment, higher BMI also correlates to higher risk of recurrence. PSA levels can be also increased by
prostatitis Prostatitis is an umbrella term for a variety of medical conditions that incorporate bacterial and non-bacterial origin illnesses in the pelvic region. In contrast with the plain meaning of the word (which means "inflammation of the prostate"), the ...
, irritation,
benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...
(BPH), and recent ejaculation, producing a
false positive A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resul ...
result. Digital rectal examination (DRE) has been shown in several studies


to produce an increase in PSA. However, the effect is clinically insignificant, since DRE causes the most substantial increases in patients with PSA levels already elevated over 4.0ng/mL. The "normal"
reference range In medicine and health-related fields, a reference range or reference interval is the range or the interval of values that is deemed normal for a physiological measurement in healthy persons (for example, the amount of creatinine in the blood, o ...
s for prostate-specific antigen increase with age, as do the usual ranges in cancer, as per table below.


PSA velocity

Despite earlier findings, recent research suggests that the rate of increase of PSA (e.g. >0.35ng/mL/yr, the 'PSA velocity') is not a more specific marker for prostate cancer than the serum level of PSA. However, the PSA rate of rise may have value in prostate cancer prognosis. Men with prostate cancer whose PSA level increased by more than 2.0ng per milliliter during the year before the diagnosis of prostate cancer have a higher risk of death from prostate cancer despite undergoing
radical prostatectomy Prostatectomy (from the Greek , "prostate" and , "excision") as a medical term refers to the surgical removal of all or part of the prostate gland. This operation is done for benign conditions that cause urinary retention, as well as for prosta ...
. PSA velocity (PSAV) was found in a 2008 study to be more useful than the PSA doubling time (PSA DT) to help identify those men with life-threatening disease before start of treatment. Men who are known to be at risk for prostate cancer, and who decide to plot their PSA values as a function of time (i.e., years), may choose to use a
semi-log plot In science and engineering, a semi-log plot/graph or semi-logarithmic plot/graph has one axis on a logarithmic scale, the other on a linear scale. It is useful for data with exponential relationships, where one variable covers a large range o ...
. An exponential growth in PSA values appears as a straight line(Archived by WebCite® at ) on a semi-log plot, so that a new PSA value significantly above the straight line signals a ''switch'' to a new and significantly higher growth rate, i.e., a higher PSA velocity.


Free 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 A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disea ...
in men with PSA levels between 4 and 10ng/mL. However, both total and free PSA increase immediately after ejaculation, returning slowly to baseline levels within 24 hours.


Inactive PSA

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.


Complexed PSA

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.


PSA in other biologic fluids and tissues

It is now clear that the term prostate-specific antigen is a
misnomer A misnomer is a name that is incorrectly or unsuitably applied. Misnomers often arise because something was named long before its correct nature was known, or because an earlier form of something has been replaced by a later form to which the name ...
: it is an
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
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. In women, PSA is found in female ejaculate at concentrations roughly equal to that found in male semen. Other than semen and female ejaculate, the greatest concentrations of PSA in biological fluids are detected in breast milk and amniotic fluid. Low concentrations of PSA have been identified in the urethral glands, endometrium, normal breast tissue and salivary gland tissue. PSA also is found in the serum of women with breast, lung, or uterine cancer and in some patients with renal cancer. Tissue samples can be stained for the presence of PSA in order to determine the origin of malignant cells that have metastasized.


Interactions

Prostate-specific antigen has been shown to
interact Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...
with protein C inhibitor. Prostate-specific antigen interacts with and activates the vascular endothelial growth factors
VEGF-C Vascular endothelial growth factor C (VEGF-C) is a protein that is a member of the platelet-derived growth factor / vascular endothelial growth factor (PDGF/VEGF) family. It is encoded in humans by the ''VEGFC'' gene, which is located on chromos ...
and VEGF-D, which are involved in tumor
angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splittin ...
and in the lymphatic
metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, the ...
of tumors.


See also

*
Tumor markers A tumor marker is a biomarker found in blood, urine, or body tissues that can be elevated by the presence of one or more types of cancer. There are many different tumor markers, each indicative of a particular disease process, and they are used ...


References


Further reading

* * * *


External links

* The
MEROPS MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibitors ...
online database for peptidases and their inhibitors
S01.162
* American Cancer Society: Detailed Guide: Prostate Cance
Can Prostate Cancer Be Found Early?
* National Cancer Institute
The Prostate-Specific Antigen (PSA) Test: Questions and Answers
*

Help us stop prostate diseases ruining lives
PSA
at Lab Tests Online
Total PSA
ELISA assay procedure * {{DEFAULTSORT:Prostate-Specific Antigen Andrology Biomarkers Blood tests EC 3.4.21 Prostate cancer Tumor markers Urology