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Metastasis (pronounced meh-TAS-ta-sis) means the spread of cancer. Cancer cells can break away from a primary tumor and travel through the bloodstream or lymphatic system to other parts of the body. The plural is metastases (pronounced meh-TAS-ta-seez).

Cancers are capable of spreading through the body by two mechanisms: invasion and metastasis. Invasion is the direct migration and penetration by cancer cells into neighboring tissues. Metastasis is the ability of cancer cells to penetrate into lymphatic and blood vessels, circulate through the bloodstream, and then grow in a new focus (metastasize) in normal tissues elsewhere in the body.

Tumors are classified as being either benign or malignant depending on whether or not they can spread by local invasion and/or metastasis. Benign tumors are tumors that cannot spread by invasion or metastasis; hence they only grow locally. Malignant tumors are tumors that are capable of spreading by invasion and metastasis. By definition, the term "cancer" applies only to malignant tumors.

When patients are diagnosed with cancer, they want to know whether their disease is local or has spread to other locations.

It is its ability to spread to other tissues and organs that makes cancer a potentially life-threatening disease, so there is great interest in understanding what makes metastasis possible for a cancerous tumor.

Cancer cells may spread to lymph nodes near the primary tumor (regional lymph nodes). This is called nodal involvement, positive nodes, or regional disease. Cancer cells can also spread to other parts of the body, distant from the primary tumor. Doctors use the term metastatic disease or distant disease to describe cancer that spreads to other organs or to lymph nodes other than those near the primary tumor.

When cancer cells spread and form a new tumor, the new tumor is called a secondary, or metastatic, tumor. The cancer cells that form the secondary tumor are like those in the original tumor. That means, for example, that if breast cancer spreads (metastasizes) to the lung, the secondary tumor is made up of abnormal breast cells (not abnormal lung cells). The disease in the lung is metastatic breast cancer (not lung cancer).

Table of contents
1 Factors involved in metastasis
2 Metastasis and primary cancer
3 Diagnosis of primary and secondary tumors
4 Treatments for metastatic cancer

Factors involved in metastasis

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 lymph 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.

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. This process of forming new blood vessels is called angiogenesis.

Tumor angiogenesis is the proliferation of a network of blood vessels that penetrates into cancerous growths, supplying nutrients and oxygen and removing waste products. Tumor angiogenesis actually starts with cancerous tumor cells releasing molecules that send signals to surrounding normal host tissue. This signaling activates certain genes in the host tissue that, in turn, make proteins to encourage growth of new blood vessels.

Metastasis and primary cancer

Metastatis theoretically always coincides with a primary cancer. It 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 tumour found. 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. In some of these cases a primary will appear later.

The use of immunohistochemistry has permitted pathologists to give an identity to many of these metastases. Imaging of the indicated area only occasionally reveals a primary however.

Diagnosis of primary and secondary tumors

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.

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 who has been treated for cancer in the past, it is more often a metastasis than another primary tumor.

In about 10% of cancer patients, a secondary tumor is diagnosed, but no primary cancer can be found, in spite of extensive tests. Doctors refer to the primary tumor as unknown or occult, and the patient is said to have cancer of unknown primary origin (CUP). 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.

Treatments for metastatic cancer

When cancer has metastasized, it may be treated with 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.