Common Cancer Diagnostic Techniques
The procedure that takes a sample of tissue to test whether a lump represents cancer is called a biopsy, and the tissue sample is called the biopsy specimen. Some types of biopsies remove an entire organ. Other types of biopsies may remove tumor samples through a thin needle or through an endoscope.
There are 2 types of needle biopsies: fine needle biopsy (also called fine needle aspiration) and core needle biopsy (also called core biopsy). Fine needle aspiration (FNA) uses a very thin needle and a syringe to withdraw a small amount of fluid and very small pieces of tissue from the tumor. The main advantages of FNA are that it does not require cutting through the skin and that in some cases it is possible to make a diagnosis the same day. The disadvantage is that sometimes this needle cannot remove enough tissue for a definite diagnosis. Core biopsy uses needles that are slightly larger than those used in FNA. They remove a small cylinder of tissue (about 1/16 inch in diameter and 1/2 inch long). The core needle biopsy is done using local anesthesia.
Excisional or incisional biopsy - with this type of biopsy, a surgeon cuts through the skin to remove the entire tumor (excisional biopsy) or a small part of a large tumor (incisional biopsy).
Endoscopic biopsy - an endoscope is a thin, flexible, lighted tube that has a lens or a video camera on the end. It can allow a doctor to look inside different parts of the body. Tissue samples can also be taken out through the endoscope to find out if cancer is present and, if so, the type.
Skin biopsies - there are many ways to take a biopsy of the skin. Shave biopsies remove the outer layers of skin and are fine for some basal cell or squamous cell skin cancers. Punch biopsies or excisional biopsies remove deeper layers of the skin, and can find out how deeply a melanoma has gone into the skin - an important factor in choosing treatment for that type of cancer.
Sentinel lymph node mapping and biopsy - lymph node mapping helps the surgeon know which lymph nodes to remove for an excisional biopsy. Sentinel node mapping and biopsy has become a common way to find out whether the cancer (especially melanoma and breast cancer) has spread to the lymph nodes. This procedure can find the lymph nodes that drain lymph fluid from the area where the cancer started. If the cancer has spread, these lymph nodes are usually the first place it will go.
Endoscopy is a medical procedure that uses tube-like instruments (called endoscopes.) These are put into the body to look inside. There are many different kinds of endoscopes, or "scopes." Some are hollow and allow the doctor to look right into the body. Others use fiber optics - flexible glass or plastic fibers that transmit light. Still others have small video cameras on the end that put pictures on computer screens. Depending on the area of the body being looked at, the endoscope may be put in through an opening like the mouth, anus, or urethra (the tube that carries urine out of the bladder). In some cases, the endoscope is put in through a small cut (incision) made in the skin. Some types of endoscopes can be used to look for cancer in people who have no symptoms. For example, colonoscopy and sigmoidoscopy are used to screen for colon and rectal cancer.
Diagnosing diseases by looking at single cells and small clusters of cells is called cytology or cytopathology. While the pieces of tissue in biopsy samples may be as small as 1/16 inch or much larger (several inches), the individual cells and the cell clusters in cytology samples are usually too small to see without a microscope. Compared with tissue biopsy, a cytology specimen usually: is easier to get; causes less discomfort to the patient; is less likely to result in serious complications; costs less. The disadvantage is that, in some cases, a tissue biopsy result is more accurate, though in many cases the cytology fluid may be just as accurate.
Body fluids - fluids from cavities and spaces in the body can be tested to see if cancer cells are present. Some of the body cavity fluids tested in this way include: urine; sputum (phlegm); spinal fluid; pleural fluid (from the space around the lungs); pericardial fluid (from the sac that surrounds the heart); ascitic fluid (from the space in the belly).
Scrape or brush cytology - another cytology technique is to gently scrape or brush some cells from the organ or tissue being tested. The best-known cytology test that samples cells in this way is the Pap test. Pap test samples are taken by using a small spatula and/or brush to remove cells from the cervix (the lower part of the uterus or womb). Other areas that can be brushed or scraped include the esophagus (swallowing tube), stomach, bronchi (breathing tubes that lead to the lungs), and mouth.
Histochemical stains - these tests use different chemical dyes that are attracted to certain substances found in some types of cancer cells. An example is the mucicarmine stain, which is attracted to mucus. Droplets of mucus inside a cell that are exposed to this stain will look pink-red under a microscope. This stain is useful if the pathologist suspects, for example, an adenocarcinoma (a glandular type of cancer) in a lung biopsy. Adenocarcinomas can produce mucus, so finding pink-red spots in lung cancer cells will tell the pathologist that the diagnosis is adenocarcinoma.
Immunohistochemical stains - immunohistochemical (IHC) or immunoperoxidase stains are another very useful category of special tests. The principle of this method is that an antibody will attach itself to certain substances (antigens) that are on or in the cell. Certain types of normal cells and cancer cells have unique different antigens. To find out if the antibodies have been attracted to the cells, chemicals are added that cause the cell to change color only if a certain antibody (and, therefore, the antigen) is present. IHC stains are useful in identifying certain types of cancers. If the cancer started in the lymph node, the diagnosis would be lymphoma. If the cancer started in another part of the body and spread to the lymph node, it might be metastatic cancer.
Electron microscopy - the typical medical lab microscope uses a beam of ordinary light to look at specimens; whereas electron microscope uses beams of electrons. The electron microscope's magnifying power is about 1,000 times greater than that of an ordinary light microscope. This degree of magnification is rarely needed in deciding whether a cell is cancer. But it sometimes helps find very tiny details of a cancer cell's structure that provide clues to the exact type of the cancer.
Flow cytometry - this test is often used to test the cells from bone marrow, lymph nodes, and blood samples. It is very accurate in finding out the exact type of leukemia or lymphoma a person has. It also helps to tell lymphomas from non-cancer lymph node diseases. A sample of cells from a biopsy, cytology specimen, or blood specimen is treated with special antibodies and passed in front of a laser beam. Each antibody sticks only to certain types of cells that contain the antigens that fit with it. If the sample contains those cells, the laser will cause them to give off light that is then measured and analyzed by a computer.
Image cytometry – similar to flow cytometry, this test uses dyes that react with DNA. But instead of suspending the cells in a stream of liquid and analyzing them with a laser, image cytometry uses a digital camera and a computer to measure the amount of DNA in cells on a microscope slide.
Cytogenetics - normal human cells contain 46 chromosomes. Some types of cancer have a unique abnormal chromosome. Recognizing the abnormal chromosome helps to identify those types of cancer. This is especially useful in diagnosing some lymphomas, leukemias, and sarcomas.
Fluorescent in situ hybridization (FISH) is a newer test that is much like cytogenetic testing. It can find most chromosome changes that can be seen under a microscope in standard cytogenetic tests. It can also find some changes too small to be seen with usual cytogenetic testing. FISH uses special fluorescent dyes that only attach to specific parts of certain chromosomes. FISH can find chromosome changes such as translocations, which are important to help classify some kinds of leukemia. This test can also show when there are too many copies of a certain gene, which sometimes can help doctors choose the best treatment options.
Molecular genetic tests can identify mutations (abnormal changes) in certain areas of DNA that are responsible for controlling cell growth. Some of these mutations may cause cancers to be especially aggressive in growing and spreading. In some cases, identifying certain mutations can help doctors choose treatments that are more likely to work.
Polymerase chain reaction (PCR) - is a very sensitive molecular genetic test for finding specific DNA sequences, such as those occurring in some cancers. Reverse transcriptase PCR (RT-PCR) is a method used to detect small amounts of RNA. RT-PCR can be used to find and classify cancer cells. RT-PCR can also be used to sub-classify cancer cells.
Gene expression microarrays - the advantage of this technology is that relative levels of hundreds or even thousands of different RNA molecules from one sample can be compared at the same time. The results tell which genes are active in a tumor.
Imaging tests are studies that make pictures (images) of what's going on inside a body. These tests use forms of energy (x-rays, sound waves, radioactive particles, or magnetic fields) that are passed through the body. The changes in energy patterns made by body tissues can be seen with special devices, which change them into pictures. These pictures can show normal body structure and function as well as abnormal ones caused by diseases such as cancer.
Computed tomography scan (CT scan, CAT scan, and spiral or helical CT) - CT scans show a slice, or cross-section, of the body. CT scans use controlled amounts of x-rays to create images. Whereas a standard x-ray uses a broad beam of radiation, a CT scan uses a pencil-thin beam to create a series of pictures taken from different angles. The image shows organs and soft tissues more clearly than standard x-rays. Because the picture is made by a computer, it can be enlarged to make it easier to see and interpret. CT scans can show a tumor's shape, size, and location, and even the blood vessels that feed the tumor - all without having to cut into the patient. CT scans are good at finding and getting information about cancer in the liver, pancreas, adrenal glands, lungs, and bones. They are also used to collect information about cancer in the large and small intestines, swallowing tube (esophagus), stomach, brain, prostate, or other organs. In recent years, spiral CT (also known as helical CT) has become the most common type of CT used. It uses a better and faster machine that uses less radiation than the original CT scanner.
Magnetic resonance imaging (MRI, magnetic resonance (MR), and nuclear magnetic resonance (NMR) imaging) - like CT scans, MRI displays a cross-section of a body. But MRI uses strong magnets instead of radiation to create the images. MRI creates pictures of soft tissue parts of the body that are sometimes hard to see using other imaging tests. MRI is good at finding and pinpointing cancer in the brain, spinal cord, head, neck, and bones and muscles. An MRI done with contrast is the best way to see brain tumors. Using MRI, doctors can sometimes tell a non-cancerous (benign) tumor from a cancerous (malignant) one.
Radiographic studies (regular x-rays and contrast studies) (also called radiographs and roentgenograms) - radiographs, most often called x-rays, produce shadow-like images of certain organs or tissues. X-rays are very good at finding certain bone problems. X-rays can show some organs or soft tissues, but MRI and CT scans often give better pictures of them. Still, x-rays are often faster, easy to get, and cost less than newer scans, so they may be used to get information quickly. An x-ray of the belly may show tumors or other diseases in organs like the intestines, stomach, liver, spleen, and kidneys. A chest x-ray can help find lung diseases, including cancer. These tests, which make a single image or series of images, are sometimes called standard radiographic studies. Mammograms (breast x-rays) are another form of radiographic study.
Special types of x-ray tests may use dyes called contrast materials. Contrast studies provide some information that standard x-ray cannot. During a contrast study, one gets a dose of a contrast material that outlines, highlights, or fills in parts of the body so that they show up more clearly on an x-ray. The contrast material may be given by mouth, as an enema, as an injection, or through a catheter put into various tissues of the body. For most of these tests, the images can be captured either on x-ray film or by a computer.
Nuclear scans (nuclear imaging, radionuclide imaging, and nuclear medicine scans) - nuclear scans make pictures based on the body's chemistry rather than on physical shapes and forms. They use substances called radionuclides (also known as tracers or radiopharmaceuticals) that release low levels of radiation. The amount of radioactivity used is very small and not known to cause harm. Body tissues affected by certain diseases, such as cancer, may absorb more or less of the tracer than normal tissues. Special cameras pick up the pattern of radioactivity to create images that show where the material travels and where it collects. The scans show certain disorders of internal organs and tissues better than standard x-ray images. Nuclear scans are used to find tumors, especially in the bones and thyroid gland. They are also used to study a cancer's stage and to decide if treatment is working.
Radionuclide scans: Radionuclides send out gamma rays which are picked up by a special camera (known as a gamma camera, rectilinear scanner, or scintiscan). The signals are processed by a computer, which turns them into 2- or 3-dimensional (3-D) images, sometimes with color added for extra clarity.
Positron emission tomography scans - positron emission tomography (PET) is a scan that uses a form of radioactive sugar. Body cells take in different amounts of the radioactive sugar, depending on how fast they are growing. Cancer cells, which grow quickly, are more likely to take up larger amounts of the sugar than normal cells. The radioactive sugar gives off tiny atomic particles called positrons, which run into electrons in the body, giving off gamma rays. A special camera picks up these rays as they leave the body and turns them into pictures. PET scans are most often used to find cancer. PET scans are especially useful for studying the brain. They are also widely used to look at cancers of the head and neck, thyroid, esophagus (swallowing tube), breast, colon, rectum, ovary, and lung, as well as melanomas and lymphomas.
PET/CT scans: A newer imaging machine combines PET scans with CT scans. PET/CT scanners give more detailed information on the location of any increased cell activity, helping doctors to pinpoint tumors. They are now commonly being used.
Ultrasound (ultrasonography, sonography, or sonogram) - an ultrasound machine creates images called sonograms by giving off high-frequency sound waves that go through a body. As the sound waves bounce off organs and tissues, they create echoes. Ultrasound is good at giving pictures of some diseases of soft tissues that do not show up well on x-rays. Ultrasound is also a good way to tell fluid-filled cysts from solid tumors because they make very different echo patterns. Ultrasound can also be used to find out how far a tumor of the esophagus (swallowing tube), rectum, or uterus (womb) has gone through the wall of the organ.
References: All the data in this article are provided by the American Cancer Society.
1. American Cancer Society. 2010
2. American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society, 2009
3. American Cancer Society: Early Detection. 2010
Tuesday, June 29, 2010
Friday, June 4, 2010
A Review Article on Genes and Proteins
In medicine, a biomarker can be referred to anything that can be used as an indicator of a particular disease state or some other biological state of an organism. Biomarkers can be genes, proteins, small molecules, or hormones. Commonly, for the purposes of diagnostics, biomarkers are broadly divided in two groups – one group encompasses genetic markers such as DNA or RNA; and the other – proteins, hormones or small molecules. In essence, DNA testing examines DNA molecule itself, and protein testing examines changes in protein concentration or alterations in its structure. To understand the difference between these two groups, it is important to define genes, proteins and how proteins are synthesized based on the genetic code.
A gene is a unit of heredity in an organism. It is normally a strand of DNA that codes for a type of protein or for an RNA chain in the organism. All proteins and functional RNA chains are specified by genes. Genes hold the information to build and maintain an organism's cells and pass genetic traits to offspring.
Proteins (also known as polypeptides) are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code (1).
In all organisms, there are two major steps separating a protein-coding gene from its protein: First, the DNA on which the gene resides must be transcribed from DNA to messenger RNA (mRNA); and, second, it must be translated from mRNA to protein. The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule itself is called a gene product.
Transcription is a genetic process that produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed. The DNA strand whose sequence matches that of the RNA is known as the coding strand and the strand from which the RNA was synthesized is the template strand.
Translation is the process by which a mature mRNA molecule is used as a template for synthesizing a new protein. Translation is carried out by ribosomes, large complexes of RNA and protein responsible for carrying out the chemical reactions to add new amino acids to a growing polypeptide chain by the formation of peptide bonds.
As mentioned above, gene tests (also called DNA-based tests) involve direct examination of the DNA molecule itself. Genetic testing allows the genetic diagnosis of vulnerabilities to inherited diseases, and can also be used to determine a child's paternity (genetic father) or a person's ancestry. Normally, every person carries two copies of every gene, one inherited from their mother, one inherited from their father. In addition to studying chromosomes to the level of individual genes, genetic testing in a broader sense includes biochemical tests for the possible presence of genetic diseases, or mutant forms of genes associated with increased risk of developing genetic disorders. Most of the time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder.
Diagnostic DNA testing is used to diagnose or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical mutations and symptoms. Diagnostic testing can be performed at any time during a person's life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a person's choices about health care and the management of the disease.
Predictive and presymptomatic types of DNA testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person's chances of developing disorders with a genetic basis.
The results of genetic tests are not always straightforward, which often makes them challenging to interpret and explain. When interpreting test results, healthcare professionals consider a person’s medical history, family history, and the type of genetic test that was done.
A positive test result means that the laboratory found a change in a particular gene, or chromosome of interest. Depending on the purpose of the test, this result may confirm a diagnosis, indicate that a person is a carrier of a particular genetic mutation, identify an increased risk of developing a disease in the future, or suggest a need for further testing. It is important to note that a positive result of a predictive or presymptomatic genetic test usually cannot establish the exact risk of developing a disorder. Also, health professionals typically cannot use a positive test result to predict the course or severity of a condition.
A negative test result means that the laboratory did not find a dangerous copy of the gene, chromosome, or protein under consideration. This result can indicate that a person is not affected by a particular disorder, is not a carrier of a specific genetic mutation, or does not have an increased risk of developing a certain disease. It is possible, however, that the test missed a disease-causing genetic alteration because many tests cannot detect all genetic changes that can cause a particular disorder. Further testing may be required to confirm a negative result.
In some cases, a negative result might not give any useful information. This type of result is called uninformative. Uninformative test results sometimes occur because everyone has common, natural variations in their DNA, called polymorphisms, that do not affect health. If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out a specific diagnosis, and it cannot indicate whether a person has an increased risk of developing a disorder. In some cases, testing other affected and unaffected family members can help clarify this type of result.
Testing for protein biomarkers is generally more straightforward – a change in the quantity of a certain biomarker normally signals of the presence of a disease or a pathological condition. For instance, it is widely known that C-reactive protein (CRP) is a marker for inflammation; or that matrix metalloproteases are markers for cancer (2,3).
Other examples include pregnancy tests or immunohistochemical tests performed by pathologists to diagnose cancer.
Modern pregnancy tests look for chemical markers associated with pregnancy. These markers are found in urine and blood, and pregnancy tests require sampling one of these substances. The most commonly used marker is human chorionic gonadotropin (hCG), that was discovered in 1930 to be produced by the trophoblast cells of the fertilised ovum (blastocyst). The presence of this marker normally indicates that a woman is pregnant.
Immunohistochemistry (IHC) is also a straightforward process of localizing antigens (proteins) in cells of a tissue section using the principle of antibodies binding specifically to antigens in biological tissues (4). It takes its name from the roots "immuno," in reference to antibodies used in the procedure, and "histo," meaning tissue. IHC is a very good detection technique and has the advantage of being able to show exactly where a given protein is located within the tissue examined. Immunohistochemical staining is widely used in diagnostic surgical pathology for typing tumors (e.g. immunostaining for e-cadherin to differentiate between DCIS (ductal carcinoma in situ: stains positive) and LCIS (lobular carcinoma in situ: does not stain positive) (5); or cytokeratins for identification of carcinomas (6).
References:
1. Ridley, M. (2006). Genome. New York, NY: Harper Perennial.
2. Eiji Sunami, Nelson Tsuno, Takuya Osada, Shinsuke Saito, Joji Kitayama, Shigeru Tomozawa, Takashi Tsuruo, Yoichi Shibata, Tetsuichiro Muto, Hirokazu Nagawa:”MMP-1 is a Prognostic Marker for Hematogenous Metastasis of Colorectal Cancer”, The Oncologist, Vol. 5, No. 2, 108-114, April 2000
3. Pia Vihinen, Veli-Matti Kähäri: “Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets”, International Journal of Cancer, Volume 99 Issue 2, Pages 157 – 166, 12 Mar 2002.
4. Ramos-Vara, JA (2005). "Technical Aspects of Immunohistochemistry". Vet Pathol 42 (4): 405–426
5. O'Malley F and Pinder S, Breast Pathology, 1st. Ed. Elsevier 2006.
6. Leader M, Patel J, Makin C, Henry K (December 1986). "An analysis of the sensitivity and specificity of the cytokeratin marker CAM 5.2 for epithelial tumours. Results of a study of 203 sarcomas, 50 carcinomas and 28 malignant melanomas". Histopathology 10 (12): 1315–24.
A gene is a unit of heredity in an organism. It is normally a strand of DNA that codes for a type of protein or for an RNA chain in the organism. All proteins and functional RNA chains are specified by genes. Genes hold the information to build and maintain an organism's cells and pass genetic traits to offspring.
Proteins (also known as polypeptides) are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code (1).
In all organisms, there are two major steps separating a protein-coding gene from its protein: First, the DNA on which the gene resides must be transcribed from DNA to messenger RNA (mRNA); and, second, it must be translated from mRNA to protein. The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule itself is called a gene product.
Transcription is a genetic process that produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed. The DNA strand whose sequence matches that of the RNA is known as the coding strand and the strand from which the RNA was synthesized is the template strand.
Translation is the process by which a mature mRNA molecule is used as a template for synthesizing a new protein. Translation is carried out by ribosomes, large complexes of RNA and protein responsible for carrying out the chemical reactions to add new amino acids to a growing polypeptide chain by the formation of peptide bonds.
As mentioned above, gene tests (also called DNA-based tests) involve direct examination of the DNA molecule itself. Genetic testing allows the genetic diagnosis of vulnerabilities to inherited diseases, and can also be used to determine a child's paternity (genetic father) or a person's ancestry. Normally, every person carries two copies of every gene, one inherited from their mother, one inherited from their father. In addition to studying chromosomes to the level of individual genes, genetic testing in a broader sense includes biochemical tests for the possible presence of genetic diseases, or mutant forms of genes associated with increased risk of developing genetic disorders. Most of the time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder.
Diagnostic DNA testing is used to diagnose or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical mutations and symptoms. Diagnostic testing can be performed at any time during a person's life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a person's choices about health care and the management of the disease.
Predictive and presymptomatic types of DNA testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person's chances of developing disorders with a genetic basis.
The results of genetic tests are not always straightforward, which often makes them challenging to interpret and explain. When interpreting test results, healthcare professionals consider a person’s medical history, family history, and the type of genetic test that was done.
A positive test result means that the laboratory found a change in a particular gene, or chromosome of interest. Depending on the purpose of the test, this result may confirm a diagnosis, indicate that a person is a carrier of a particular genetic mutation, identify an increased risk of developing a disease in the future, or suggest a need for further testing. It is important to note that a positive result of a predictive or presymptomatic genetic test usually cannot establish the exact risk of developing a disorder. Also, health professionals typically cannot use a positive test result to predict the course or severity of a condition.
A negative test result means that the laboratory did not find a dangerous copy of the gene, chromosome, or protein under consideration. This result can indicate that a person is not affected by a particular disorder, is not a carrier of a specific genetic mutation, or does not have an increased risk of developing a certain disease. It is possible, however, that the test missed a disease-causing genetic alteration because many tests cannot detect all genetic changes that can cause a particular disorder. Further testing may be required to confirm a negative result.
In some cases, a negative result might not give any useful information. This type of result is called uninformative. Uninformative test results sometimes occur because everyone has common, natural variations in their DNA, called polymorphisms, that do not affect health. If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out a specific diagnosis, and it cannot indicate whether a person has an increased risk of developing a disorder. In some cases, testing other affected and unaffected family members can help clarify this type of result.
Testing for protein biomarkers is generally more straightforward – a change in the quantity of a certain biomarker normally signals of the presence of a disease or a pathological condition. For instance, it is widely known that C-reactive protein (CRP) is a marker for inflammation; or that matrix metalloproteases are markers for cancer (2,3).
Other examples include pregnancy tests or immunohistochemical tests performed by pathologists to diagnose cancer.
Modern pregnancy tests look for chemical markers associated with pregnancy. These markers are found in urine and blood, and pregnancy tests require sampling one of these substances. The most commonly used marker is human chorionic gonadotropin (hCG), that was discovered in 1930 to be produced by the trophoblast cells of the fertilised ovum (blastocyst). The presence of this marker normally indicates that a woman is pregnant.
Immunohistochemistry (IHC) is also a straightforward process of localizing antigens (proteins) in cells of a tissue section using the principle of antibodies binding specifically to antigens in biological tissues (4). It takes its name from the roots "immuno," in reference to antibodies used in the procedure, and "histo," meaning tissue. IHC is a very good detection technique and has the advantage of being able to show exactly where a given protein is located within the tissue examined. Immunohistochemical staining is widely used in diagnostic surgical pathology for typing tumors (e.g. immunostaining for e-cadherin to differentiate between DCIS (ductal carcinoma in situ: stains positive) and LCIS (lobular carcinoma in situ: does not stain positive) (5); or cytokeratins for identification of carcinomas (6).
References:
1. Ridley, M. (2006). Genome. New York, NY: Harper Perennial.
2. Eiji Sunami, Nelson Tsuno, Takuya Osada, Shinsuke Saito, Joji Kitayama, Shigeru Tomozawa, Takashi Tsuruo, Yoichi Shibata, Tetsuichiro Muto, Hirokazu Nagawa:”MMP-1 is a Prognostic Marker for Hematogenous Metastasis of Colorectal Cancer”, The Oncologist, Vol. 5, No. 2, 108-114, April 2000
3. Pia Vihinen, Veli-Matti Kähäri: “Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets”, International Journal of Cancer, Volume 99 Issue 2, Pages 157 – 166, 12 Mar 2002.
4. Ramos-Vara, JA (2005). "Technical Aspects of Immunohistochemistry". Vet Pathol 42 (4): 405–426
5. O'Malley F and Pinder S, Breast Pathology, 1st. Ed. Elsevier 2006.
6. Leader M, Patel J, Makin C, Henry K (December 1986). "An analysis of the sensitivity and specificity of the cytokeratin marker CAM 5.2 for epithelial tumours. Results of a study of 203 sarcomas, 50 carcinomas and 28 malignant melanomas". Histopathology 10 (12): 1315–24.
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