Dictionary:
me·tas·ta·sis (mĭ-tăs'tə-sĭs)  |
[Greek, from methistanai, to change : meta-, meta- + histanai, to cause to stand, place.]
metastatic met'a·stat'ic (mĕt'ə-stăt'ĭk) adj.| 5min Related Video: metastasis |
| Oncology Encyclopedia: Metastasis |
Key Terms: Angiogenesis, Apoptosis, Basement membrane, Embolus, Epithelium, Extracellular matrix, Extravasation, Micrometastasis, Multicentric, Oncogene, Replication, Tumor markers, Tumor necrosis factor, Tumor suppressor gene, Vascular endothelial growth factor.
Definition
The ability to invade and metastasize are the defining characteristics of a cancer. Invasion refers to the ability of cancer cells to penetrate through the membranes that separate them from healthy tissues and blood vessels. Metastasis can refer either to the spread of cancer cells to other parts of the body, or to the condition produced by this spread. The English word metastasis (plural, metastases) comes from a Greek word that means "a change." The tumors produced by metastasis sometimes are called secondary tumors. metastasis is responsible for 90% of the deaths caused by cancer.
Description
Metastasis is a complex multi-step process that begins with changes in the genetic material of a cell (carcinogenesis) followed by the uncontrolled multiplication of altered cells. It continues with the development of a new blood supply for the tumor (angiogenesis), invasion of the circulatory system, dispersal of small clumps of tumor cells to other organs or parts of the body, and the growth of secondary tumors in those sites.
Carcinogenesis and Genetic Mutations
The first step in cancer development is a change or mutation of the DNA in the chromosomes of a cell. Mutations can be triggered by a number of different factors, including:
Other mutations in a cell's DNA occur for reasons that are not yet fully understood.
Steps in the Development of Metastases
Cell Alteration and Replication
Most cancer cells originate within the epithelium, which is a layer of tissue that covers body surfaces and lines the inner surfaces of body cavities and blood vessels. Cancer cells in epithelial tissue are known to be genetically unstable and to have a high mutation rate. Most cancers, in fact, are the end result of multiple genetic alterations both in oncogenes and tumor suppressor genes. The activation of oncogenes is accompanied by the loss or deactivation of tumor suppressor genes, which means that one of the body's normal lines of defense against uncontrolled cell proliferation is disabled just when it is most needed.
Following these alterations in its genetic material, the cell replicates, or copies itself at a faster rate. In some instances, a mutation prevents the cell's apoptosis, or programmed self-destruction. Apoptosis, which is also sometimes called "cell suicide," normally occurs when a cell recognizes some damage to its DNA and dies. The protein produced by the p53 gene ordinarily encourages apoptosis in cells with defective DNA, but these cells are more likely to survive and replicate if the p53 gene has been altered or deactivated.
Breaking Through the Basement Membrane
Once a cancer develops, the first stage in the development of metastasis is the tumor's penetration of the basement membrane, which separates epithelial tissue from underlying connective tissue. The basement membrane is a specialized layer of extracellular matrix, which is a mass of connective tissue fibers and proteins that support and nourish the body's connective tissues. Under normal circumstances, the extracellular matrix is a barrier that keeps cells from moving away from their sites of origin. Cancer cells, however, secrete several different types of enzymes that digest the proteins in the basement membrane. When the membrane has been sufficiently weakened, the tumor can push through it.
Angiogenesis
Angiogenesis is the process in which a tumor creates its own blood supply by releasing growth factors—particularly a substance called vascular endothelial growth factor, or VEGF—that attract vascular cells that begin to migrate toward the tumor. The vascular cells eventually form new blood vessels within the tumor. Angiogenesis is sometimes called vascularization, which means blood vessel formation. Angiogenesis is a significant step in the development of metastasis for two reasons: the formation of blood vessels in the tumor supplies the tumor with nutrients that speed up its growth; these vessels also provide pathways for cancer cells to travel from the primary tumor to other organs. A similar process of vessel formation involves the lymph system.
Angiogenesis may occur at about the same time that the tumor breaks through the basement membrane, but it can also take place at an earlier point in the tumor's growth.
Invasion and Embolization
After the tumor's new blood vessels have formed, individual cancer cells break off from the tumor and travel through these new vessels into the body's main circulatory system. These cells are sometimes called micrometastases. Even a small tumor can shed as many as a million cancer cells each day into the blood and lymph vessels. Most of these cells die soon after entering the blood stream or lymph vessels. Sometimes, however, the cancer cells may travel as small clumps of cells called emboli. A protein called fibrin, which ordinarily is formed when blood clots, surrounds each embolus. The fibrin appears to protect the embolus of cancer cells as it moves through the circulatory system, and may increase its chances for survival when it arrives in the capillaries (small blood vessels) that supply another organ or area of the body.
Extravasation and Formation of Secondary Tumors
Extravasation refers to the cancer cell's breaking out through the wall of the capillary where it has been stopped and invading the tissue around the capillary. In order to extravasate, the tumor cell must attach itself to the wall of the capillary. Once it has attached itself, it can work its way through the tissue lining the blood vessel, the vessel wall itself, and the basement membrane covering the blood vessel. The tumor cell can then begin to replicate itself and start the process of angiogenesis, thus forming a metastasis or secondary tumor in its new location. The secondary tumor can eventually release its own cancer cells into the circulation and produce further metastases.
Most tumor cells do not survive in the blood stream long enough to extravasate and form metastases. The longer the cells are in the circulation, the more likely they are to die. The chances of a given tumor cell's surviving the journey and forming a metastasis in its new site have been variously estimated as one in 10,000 or as less than one in one million. Researchers have asked whether the tumor cells that do produce metastases are random survivors or whether they have special capacities for survival and reproduction. Recent studies indicate that cells from the same tumor vary in their metastatic potential; those that eventually form metastases have a higher degree of malignancy.
Diagnosis and Monitoring of Metastases
Some primary cancers, such as lung and ovarian cancers, begin to shed tumor cells that form metastases elsewhere in the body before the primary cancer is large enough to be detected by standard diagnostic techniques. Marker molecules that are given off by micrometastases circulating in the bloodstream can now be detected.
Tumor markers are substances produced either by tumors themselves or by the body in response to a tumor. The blood levels of tumor markers can be used to evaluate the recurrence or spread of cancer and the patient's response to treatment. Some commonly used tumor markers include: prostate-specific antigen (PSA) for prostate cancer; prostatic acid phosphatase (PAP) for prostate cancer that has metastasized, testicular cancer and leukemia; and CA 125 (Cancer antigen 125) for recurrence of ovarian cancer. It also detects cancers of the uterus, liver, pancreas, colon, cervix, lung, and digestive tract, as well as several others.
DNA analysis can be used to distinguish metastatic tumors from multicentric tumors. A multicentric cancer is one that appears simultaneously in several different parts of the body, as distinct from cancers with primary and secondary (metastatic) tumors. Mutations in the p53 tumor suppressor gene have been used as "genetic fingerprints" to identify differences between multicentric and metastatic tumors.
Specific Types of Metastases
Brain
Symptoms
Metastatic tumors to the brain usually come to the doctor's attention in the same way as primary tumors—they cause increased pressure inside the head, disturbances of brain functions, or both. Common symptoms of brain metastases include headaches, seizures, loss of sensation or balance, or personality changes.
Sources
The most common source of brain metastases is primary cancer of the lung. Other primary sources include malignant melanomas and cancers of the breast, kidney, or digestive tract.
Diagnosis
Secondary brain tumors are usually detected on (computed tomography) (CT) scans or (magnetic resonance imaging) (MRI) studies.
Treatment
If the patient has only one secondary tumor in the brain, it is sometimes possible to remove it surgically and then treat with radiation. Otherwise, radiation is used by itself to treat the tumors. Steroids may be given to reduce or lower swelling of the brain, treating the headaches and other symptoms. Chemotherapy has only a limited role in treating brain metastases, because most chemotherapy drugs cannot cross the blood-brain barrier. However, intrathecal chemotherapy (chemotherapy drugs injected directly into the spinal fluid) can have a role in treating brain metastases. Patients with multiple metastases in the brain or widespread cancer elsewhere in the body have a poor prognosis. Treatments that are still under evaluation include laser-assisted surgery and biological response modifiers.
Bone
Symptoms
Primary bone cancers are less common than bone metastases. Bone metastases, in fact, are a common cause of pain in many patients with late-stage cancer. Metastases in the spine can compress the spinal cord and damage the nervous system. Bone metastases also make bones more prone to fracture.
Sources
Breast, lung, and prostate cancer are responsible for about 80% of bone metastases; over half of patients with these three types of primary cancer will develop bone metastases. Patients with lung cancer that has metastasized to bone live on average less than six months, but breast and prostate cancer patients may have lengthy periods of survival with bone metastases.
Bone metastases usually are caused by tumor cells carried through the bloodstream, and are typically multiple. About 70% of bone metastases occur in the ribs, spine, sacrum (lowest portion of spine, attached to pelvis), or head; most of the remainder occur in the long bones of the body.
Diagnosis
Bone metastases usually are detected by bone scans, CT scans, or MRIs, and confirmed by a biopsy. In 2003, reports showed that positron emission tomography (PET) scans were effective in detecting certain types of bone mestasteses from lung and breast cancer and from lymphoma.
Treatment
Bone metastases are treated with hormonal or systemic chemotherapy and/or radiation therapy. Metastases in the spine may require surgical removal of part of the vertebrae (laminectomy) followed by radiation treatment to prevent compression of the spinal cord. Surgery also may be performed if there is a risk of fracture.
As of May 2001, two new drugs show promise as treatments for bone metastases. One is a generic drug called clodronate, which is taken by mouth, and the other is a medication called Atrasentan. Atrasentan was tested on patients in advanced stages of bone metastases who were no longer responding to other forms of treatment.
Lung
Sources
Metastatic tumors in the lungs may result either from primary cancer of the lung or from malignancies elsewhere in the body that spread to the lungs through the circulatory system or by direct extension. The incidence of metastatic cancer to the lung is six in 100,000 people. Almost any type of cancer can metasta-size to the lung, but the most common tumors that spread to the lung are breast cancer, sarcomas, non-Hodgkin's lymphoma, neuroblastoma, and Wilms' tumor. Between 20% and 54% of patients dying of cancer are found to have metastases in the lungs.
Diagnosis
Diagnosis is usually the appearance of a group of masses on a chest x ray. Evaluation of lung metastases is first directed at diagnosing/locating the primary tumor.
Treatment
Secondary lung cancers are treated primarily by appropriate systemic therapy for the primary tumor. Surgery for secondary lung tumors may be beneficial if there are four or less metastases. Surgical removal of tumors metastatic to the lung is usually performed only if: the primary tumor is treatable, all metastases can be removed, chemotherapy or other nonsurgical approaches cannot be used, and if there are no metastases elsewhere in the patient's body. If the primary cancer is a malignant melanoma and there is only one secondary tumor, surgery may be an option. (Surgery is usually not performed if the primary cancer is a malignant melanoma and there is more than one secondary tumor.) The five-year survival rate for surgical treatment of secondary tumors to the lung is 20%-35%.
Liver
The most common form of liver cancer is metastatic; in fact, metastases in the liver are often the first noticeable evidence of a primary cancer located elsewhere in the body. In the liver, finding multiple metastases is more common than finding a single tumor. The liver's important role within the circulatory system makes it a common stopping point for tumor emboli carried in the blood from other organs.
Sources
The most common sites of primary tumors that metastasize to the liver are the lungs, breasts, colon, pancreas, and stomach.
Diagnosis
The diagnosis of metastatic liver cancer is usually difficult unless the patient's primary tumor is in advanced stages of disease. Ultrasound, CT scans, and liver function tests are used to screen patients with a known cancer for metastases in the liver, but the results are not fully reliable. A definitive diagnosis depends on biopsy of liver tissue.
Treatment
Metastatic cancer to the liver is considered incurable. Systemic chemotherapy may temporarily shrink tumors in the liver and extend the patient's life span but does not cure the cancer. Radiation treatment may relieve pain but is not otherwise helpful. Some doctors may recommend surgical removal of liver metastases, particularly if the primary tumor is in the colon and there is a solitary metastasis, but others do not favor this approach. The five-year survival rate for surgical removal of liver metastases is 20%-30%.
Metastatic Cancers of Unknown Primary Origin
Between 0.5% and 7% of all cancers are carcinomas of unknown primary origin, or CUPs. The patient's history and physical examination should be analyzed for signs of breast, prostate, pelvic, rectal, and gastrointestinal cancers. The pattern of spread of a CUP may indicate whether the primary tumor is above or below the diaphragm; lung metastases are twice as common with primary tumors found to be above the diaphragm, while liver metastases are more common if the primary site is below the diaphragm.
Metastases of unknown primary origin are usually treated by chemotherapy—either cisplatin/carboplatin, doxorubicin or paclitaxel. In most cases, the patient's prognosis is poor; the average length of survival is three to four months, with fewer than 10% of patients surviving five years. Male sex and involvement of the liver are negative factors in the prognosis.
Treatment
Surgery
Surgery as a method of cancer treatment has limitations in the therapy of metastatic cancer. It is sometimes used to remove large secondary tumors that are causing pain or interfering with body functions. It also may offer a survival advantage over other therapies, as with limited metastases to the lung or liver.
Chemotherapy
Chemotherapy is frequently used to treat micrometastases that have entered the patient's bloodstream or lymphatic system. Systemic chemotherapy is the only type of treatment that can act at multiple sites simultaneously. Because of some chemotherapy drugs' side effects and risks (for example, nausea and vomiting, some drugs are implicated in causing some cancers), the likelihood of tumor responsiveness needs to be balanced with the patient's quality of life when selecting chemotherapy.
Radiation
Radiation therapy can be effective in the treatment of metastatic disease, especially for metastases to the brain and bones. It is limited, however, because it treats only a limited area. One complication that is possible with radiation therapy is that it has been associated with an increased rate of secondary cancers in patients who have been previously treated for malignancies. The risk is particularly high in patients who were treated with a combination of radiation and chemotherapy.
Immunotherapy
Immunotherapy, or immunologic therapy, is a modality, or method, of cancer treatment that is still in its experimental stages. It mobilizes the patient's own immune system to fight cancer cells. Immunotherapy is being evaluated in the treatment of metastatic melanoma, renal cell carcinoma, breast tumors, and other tumors. Some of the substances that are being tested in clinical trials are produced by the human body, while others are made in laboratories. The major categories of substances used in immunotherapy include:
Newer Therapies for Metastatic Cancer
Recent advances in understanding the process of metastasis have led to some new approaches to treatment.
Gene Therapy
Some researchers are investigating ways to replace a mutated p53 tumor suppressor gene, or to inhibit an activated ras oncogene. Another approach involves the use of angiogenesis inhibitors to suppress metastatic tumors. An antibody to VEGF, called anti-VEGF, is presently being used in clinical trials for patients with late-stage colon, breast, and lung cancers. A second angiogenesis inhibitor that is being tested is endostatin.
Other researchers are studying substances that trigger apoptosis in defective cells or prevent the uncontrolled multiplication of tumor cells.
Isolated Perfusion
Isolated perfusion is the treatment of metastatic melanoma and sarcoma to the extremities by isolating the vasculature (blood vessels) of the affected extremity, and then delivering high doses of chemotherapeutic drugs directly to the area of metastatic disease. The limb is then flushed before re-establishing circulation. With this technique, it becomes possible to deliver doses of drugs regionally that would otherwise be very toxic or lethal if delivered systemically.
HYPERTHERMIA Hyperthermia is the use of therapeutic heat to treat cancers on and inside the body. The goal of hyperthermia is to shrink and destroy cancer without harming noncancerous cells. The treatment can be delivered directly to the tumor, to an area of the body, or to the whole body. Research has established that the effectiveness of some forms of radiation therapy and chemotherapy are enhanced when combined with hyperthermia. In 2001, the American Cancer Society acknowledged that hyperthermia could the cells of some cancers more responsive to treatment, but still considered the treatment experimental, especially in whole-body form. The National Institutes of Health are sponsoring ongoing clinical trials studying hyperthermia. Patients with extensive metastasis may not be good candidates for hyperthermia.
Alternative and Complementary Therapies
The National Center for Complementary and Alternative Medicine (NCCAM) is sponsoring new as well as ongoing trials of alternative treatments for metastatic cancer. One ongoing trial involves PC-SPES, a combination of eight Chinese herbs that is used to treat prostate cancer. Other trials are evaluating the use of herbal remedies to treat the side effects of chemotherapy. The National Cancer Institute (NCI) makes information about ongoing clinical trials available. Patients can contact the NCI or the NCCAM at the numbers and web sites listed below.
Resources
Books
Aminoff, Michael J., MD, FRCP. "Nervous System." Chapter 24 In Current Medical Diagnosis & Treatment 2001, edited by L. M. Tierney, Jr., MD, et al., 40th ed. New York: Lange Medical Books/McGraw-Hill, 2001.
Beers, Mark H., MD, and Robert Berkow, MD, editors. "Hematology and Oncology." Section 11 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Chesnutt, Mark S., MD, and Thomas J. Prendergast, MD. "Lung." Chapter 9 in Current Medical Diagnosis & Treatment 2001, edited by L. M. Tierney, Jr., MD, et al., 40th ed. New York: Lange Medical Books/McGraw-Hill, 2001.
Rugo, Hope S., MD. "Cancer." Chapter 4 In Current Medical Diagnosis & Treatment 2001, edited by L. M. Tierney, Jr., MD, et al., 40th ed. New York: Lange Medical Books/McGraw-Hill, 2001.
Shaffrey, Mark E., MD, and Edward R. Laws, MD. "Brain Tumors." In Conn's Current Therapy 2001, edited by Robert E. Rakel, MD. and Edward T. Bope, MD. Philadelphia: W. B. Saunders Company, 2001.
Periodicals
Fidler, Isaiah J. "Melanoma Metastasis." Cancer Control Journal 2, no. 5 (2000).
"PET Effective in Detecting of Osseous Metastasis from Several Malignancies." Cancer Weekly December 30, 2003: 141.
Organizations
American Cancer Society (ACS). 1599 Clifton Road, NE, Atlanta, GA 30329. (404) 320-3333 or (800) ACS-2345. Fax: (404) 329-7530. Web site:
National Cancer Institute, Office of Cancer Communications. 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 4-CANCER (1-800-422-6237). TTY: (800) 332-8615. Web site:
NIH National Center for Complementary and Alternative Medicine (NCCAM) Clearinghouse. P. O. Box 8218, Silver Spring, MD 20907-8218. TTY/TDY: (888) 644-6226. Fax: (301) 495-4957. Web site:
Office of Cancer Complementary & Alternative Medicine of the National Cancer Institute (OCCAM). Email: ncioccam1-r@mail.nih.gov. Web site:
Other
National Center for Environmental Research, U.S. Environmental Protection Agency. Web site:
—Rebecca J. Frey, Ph.D.; Teresa G. Odle
| World of the Body: metastasis |
Transfer of disease from one part of the body to another. The term is most commonly used in relation to tumours, when cancerous cells from the primary tumour break away, are carried in the blood or lymph, and lodge elsewhere, where a secondary tumour then forms.
— Alan W. Cuthbert
See cancer.
| Dental Dictionary: metastasis |
The transfer of a disease by blood vessels, lymph vessels, or the respiratory tract (through aspiration) from one organ or region to another not directly contiguous with it. Usually used in reference to malignant tumor cells, but bacteria can also metastasize (for example, in focal infection).
Metastasis. (Thibodeau/Patton, 2002)
| Veterinary Dictionary: metastasis |
Pl. metastases [Gr.]
1. the transfer of disease from one organ or part to another not directly connected with it. It may be due either to the transfer of pathogenic microorganisms (e.g. tubercle bacilli) or to the transfer of cells, as in malignant tumors.
2. metastases, growths of pathogenic microorganisms or of abnormal cells distant from the site primarily involved by the morbid process.
See also cancer.
| Wikipedia: Metastasis |
| cancer Image = | |
|---|---|
| Classification and external resources | |
| DiseasesDB | 28954 |
| MedlinePlus | 002260 |
Metastasis (Greek: displacement, μετά=next + στάσις=placement, plural: metastases), or metastatic disease, sometimes abbreviated mets, is the spread of a disease from one organ or part to another non-adjacent organ or part. Only malignant tumor cells and infections have the established capacity to metastasize; however, this is recently reconsidered by new research.[1][2][3]
Cancer cells can break away, leak, or spill from a primary tumor, enter lymphatic and blood vessels, circulate through the bloodstream, and be deposited within normal tissue elsewhere in the body. Metastasis is one of three hallmarks of malignancy (contrast benign tumors).[4] Most tumors and other neoplasms can metastasize, although in varying degrees (e.g., glioma and basal cell carcinoma rarely metastasize).[4]
When tumor cells metastasize, the new tumor is called a secondary or metastatic tumor, and its cells are like those in the original tumor. This means, for example, that, if breast cancer metastasizes to the lungs, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called metastatic breast cancer, not lung cancer.
Contents |
Metastatic tumors are very common in the late stages of cancer. The spread of metastases may occur via the blood or the lymphatics or through both routes. The most common places for the metastases to occur are the lungs, liver, brain, and the bones.[5] There is also a propensity for certain tumors to seed in particular organs. This was first discussed as the "seed and soil" theory by Stephen Paget over a century ago in 1889. For example, prostate cancer usually metastasizes to the bones. In a similar manner, colon cancer has a tendency to metastasize to the liver. Stomach cancer often metastasizes to the ovary in women, then it is called a Krukenberg tumor. It is difficult for cancer cells to survive outside their region of origin, so in order to metastasize they must find a location with similar characteristics.[citation needed] In 1928 James Ewing challenged the "seed and soil" theory and proposed that metastasis occurs purely by anatomic and mechanical routes.
For example, breast tumor cells, which gather calcium ions from breast milk, metastasize to bone tissue, where they can gather calcium ions from bone. Malignant melanoma spreads to the brain, presumably because neural tissue and melanocytes arise from the same cell line in the embryo.[6]
Cancer cells may spread to lymph nodes (regional lymph nodes) near the primary tumor. This is called nodal involvement, positive nodes, or regional disease. ("Positive nodes" is a term that would be used by medical specialists to describe a patient's condition, meaning that the patient's lymph nodes near the primary tumor tested positive for malignancy. It is common medical practice to test by biopsy at least two lymph nodes near a tumor site when doing surgery to examine or remove a tumor.) Localized spread to regional lymph nodes near the primary tumor is not normally counted as metastasis, although this is a sign of worse prognosis. Transport through lymphatics is the most common pathway for the initial dissemination of carcinomas. [4]
In addition to the above routes, metastasis may occur by direct seeding, called transcoelomic spread. This is generally only seen in the peritoneal or pleural cavities by ovarian tumours and mesotheliomas respectively.[7]
Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream or the lymphatic system. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissue. By degrading these proteins, cancer cells are able to breach the ECM and escape. When oral cancers metastasize, they commonly travel through the lymph system to the lymph nodes in the neck. The body resists metastasis by a variety of mechanisms through the actions of a class of proteins known as metastasis suppressors, of which about a dozen are known.[8]
Cancer researchers studying the conditions necessary for cancer metastasis have discovered that one of the critical events required is the growth of a new network of blood vessels, called tumor angiogenesis.[9] It has been found that angiogenesis inhibitors would therefore prevent the growth of metastases. [4]
It is theorized that metastasis always coincides with a primary cancer, and, as such, is a tumor that started from a cancer cell or cells in another part of the body. However, over 10% of patients presenting to oncology units will have metastases without a primary tumor found. In these cases, doctors refer to the primary tumor as "unknown" or "occult," and the patient is said to have cancer of unknown primary origin (CUP) or Unknown Primary Tumors (UPT). It is estimated that 3% of all cancers are of unknown primary origin.[10] Studies have shown that, if simple questioning does not reveal the cancer's source (coughing up blood—"probably lung", urinating blood—"probably bladder"), complex imaging will not either.[10] In some of these cases a primary tumor may appear later.
The use of immunohistochemistry has permitted pathologists to give an identity to many of these metastases. However, imaging of the indicated area only occasionally reveals a primary. In rare cases (e.g., of melanoma), no primary tumor is found, even on autopsy. It is therefore thought that some primary tumors can regress completely, but leave their metastases behind.
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The symptoms of metastasis varies with location of the tumors.
Initially, nearby lymph nodes are struck early.[11] Lungs, bones, liver, and brain are the most common metastasis locations from solid tumors.[11]
Although advanced cancer may cause pain, it is often not the first symptom.
Some patients, however, don't show any symptoms.[11]
The cells in a metastatic tumor resemble those in the primary tumor. Once the cancerous tissue is examined under a microscope to determine the cell type, a doctor can usually tell whether that type of cell is normally found in the part of the body from which the tissue sample was taken.
For instance, breast cancer cells look the same whether they are found in the breast or have spread to another part of the body. So, if a tissue sample taken from a tumor in the lung contains cells that look like breast cells, the doctor determines that the lung tumor is a secondary tumor. Still, the determination of the primary tumor can often be very difficult, and the pathologist may have to use several adjuvant techniques, such as immunohistochemistry, FISH (fluorescent in situ hybridization), and others. Despite the use of techniques, in some cases the primary tumor remains unidentified.
Metastatic cancers may be found at the same time as the primary tumor, or months or years later. When a second tumor is found in a patient that has been treated for cancer in the past, it is more often a metastasis than another primary tumor.
It was previously thought that most cancer cells have a low metastatic potential and that there are rare cells that develop the ability to metastasize through the development of somatic mutations.[12] According to this theory, diagnosis of metastatic cancers is only possible after the event of metastasis. Traditional means of diagnosing cancer (e.g. a biopsy) would only investigate a subpopulation of the cancer cells and would very likely not sample from the subpopulation with metastatic potential.[13]
The somatic mutation theory of metastasis development has not been substantiated in human cancers. Rather, it seems that the genetic state of the primary tumor reflects the ability of that cancer to metastasize.[13] Research comparing gene expression between primary and metastatic adenocarcinomas identified a subset of genes whose expression could distinguish primary tumors from metastatic tumors, dubbed a "metastatic signature."[13] Up-regulated genes in the signature include: SNRPF, HNRPAB, DHPS and securin. Actin, myosin and MHC class II down-regulation was also associated with the signature. Additionally, the metastatic-associated expression of these genes was also observed in some primary tumors, indicating that cells with the potential to metastasize could be identified concurrently with diagnosis of the primary tumor.[14]
Expression of this metastatic signature has been correlated with a poor prognosis and has been shown to be consistent in several types of cancer. Prognosis was shown to be worse for individuals whose primary tumors expressed the metastatic signature.[13] Additionally, the expression of these metastatic-associated genes was shown to apply to other cancer types in addition to adenocarcinoma. Metastases of breast cancer, medulloblastoma and prostate cancer all had similar expression patterns of these metastasis-associated genes.[13]
The identification of this metastasis-associated signature provides promise for identifying cells with metastatic potential with the primary tumor and hope for improving the prognosis of these metastatic-associated cancers. Additionally, by identifying the genes whose expression is changed in metastasis offers potential targets to inhibit metastasis.[13]
Treatment and survival is determined by whether or not a cancer is local or has spread to other locations. If the cancer spreads to other tissues and organs, it may decrease a patient's likelihood of survival. However, there are some cancers (i.e., leukemia, cancer of the blood) that can kill without spreading at all.
When cancer has metastasized, it may be treated with radiosurgery, chemotherapy, radiation therapy, biological therapy, hormone therapy, surgery or a combination of these. The choice of treatment generally depends on the type of primary cancer, the size and location of the metastasis, the patient's age and general health, and the types of treatments used previously. In patients diagnosed with CUP, it is still possible to treat the disease even when the primary tumor cannot be located.
The treatment options currently available are rarely able to cure metastatic cancer, though some tumors, such as testicular cancer and thyroid cancer, are usually still curable.
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Look up metastasis in Wiktionary, the free dictionary. |
Medical information about metastatic cancer
Charities and advocacy groups dealing with metastatic cancer
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| Translations: Metastasis |
Nederlands (Dutch)
metastase (verandering van positie/vorm), uitzaaiing
Français (French)
n. - métastase
Deutsch (German)
n. - (Med.) Metastasierung
Ελληνική (Greek)
n. - (ιατρ.) μετάσταση
Português (Portuguese)
n. - metástase (f) (Med.)
Русский (Russian)
метастаз, метаболизм, трансформация
Español (Spanish)
n. - metástasis
Svenska (Swedish)
n. - metastas
中文（简体）(Chinese (Simplified))
转移, 急转换, 新陈代谢
中文（繁體）(Chinese (Traditional))
n. - 轉移, 急轉換, 新陳代謝
한국어 (Korean)
n. - 전이, 변태, 갑자기 변화함
العربيه (Arabic)
(الاسم) انتقال, تحول تبصيري
עברית (Hebrew)
n. - שינוי מצב, תמורה של חומרים, שינוי מקום, התפתחות גרורות של גידולים ממאירים בגוף, גרורה של גידול ממאיר
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Copyrights:
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 | Dictionary. The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2009. Published by Houghton Mifflin Company. All rights reserved. Read more |
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| Oncology Encyclopedia. Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved. Read more |
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| World of the Body. The Oxford Companion to the Body. Copyright © 2001, 2003 by Oxford University Press. All rights reserved. Read more |
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| Dental Dictionary. Mosby's Dental Dictionary. Copyright © 2004 by Elsevier, Inc. All rights reserved. Read more |
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| Veterinary Dictionary. Saunders Comprehensive Veterinary Dictionary 3rd Edition. Copyright © 2007 by D.C. Blood, V.P. Studdert and C.C. Gay, Elsevier. All rights reserved. Read more |
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| Wikipedia. This article is licensed under the Creative Commons Attribution/Share-Alike License. It uses material from the Wikipedia article "Metastasis". Read more |
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| Translations. Copyright © 2007, WizCom Technologies Ltd. All rights reserved. Read more |
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