Tumour Progression

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Tumours, both malignant and benign, ''present'' (that is, first become observable) as lumps or masses caused by the abnormal growth of cells. Many benign tumours are encased in a well-formed capsule. Malignant tumours, on the other hand, lack a true capsule and, even when limited to a specific location, invariably can be seen to have infiltrated surrounding tissues. The ability to invade adjacent tissues is a major characteristic delineating malignant tumours from benign tumours.

A tumour mass is composed not only of abnormal tumour cells but also of normal host cells that have been developed to nourish the tumour as well as immune cells that have been stimulated to react to the tumour. The ''healthy'' or ''normal'' component of the tumour is referred to as the tumour stroma.

As stated above, one of the fundamental characteristics of cancer cells is their uncontrolled growth. Through the microscope this behaviour is seen in an increased rate of cell division and in the failure of tumour cells to die. The rate of tumour growth is determined by comparing the excess of cell production with cell loss. For a transformed tumour cell to produce a tumour of about one billion cells (a mass that weighs about 1 gram [0.04 ounce], the size at which it becomes clinically detectable), the cell must double its population 30 times.

A tumour nodule can grow to only a certain diameter (1 to 2 millimetres [0.04 to 0.08 inch]) before the cells are too distant from the nutrients and oxygen that they need to survive. For tumour expansion to occur, new capillaries (tiny blood vessels) must form within the tumour — a process called vascularization, or angiogenesis. Angiogenesis is a normal process in the body's replacement of damaged tissue, but it can also occur under abnormal conditions, as in tumour progression. At some point, after months or even years as a harmless cluster of cells, tumours may suddenly begin to generate blood vessels — apparently because they develop the ability to synthesize certain growth factors that stimulate the formation of vessels.

Once they have begun to grow, tumours are able to sustain their own growth in a semi-independent fashion. This results from growth factors produced by the tumour cells themselves (a self-stimulatory process called autocriny) and by the stromal cells (a process called paracriny).

Cancer cells can be distinguished from normal cells, and even from benign tumour cells, by microscopic examination. Differences in appearance include inconsistencies in size and shape and misshapen internal structures such as the nucleus, where genetic material is found. Genetic instability of the cell often gives rise to abnormal cells with giant nuclei that contain enormous amounts of deoxyribonucleic acid (DNA). When these highly abnormal cells divide by mitosis, the number of chromosomes formed is abnormally elevated, and the mitotic figures (the structures that help to coordinate the division of the chromosomes) are often distorted. Cancer cells also tend to be less well-differentiated than normal cells, a characteristic that is called anaplasia. When a malignant tumour no longer resembles the tissue of origin, it is said to be undifferentiated, or anaplastic.

Precancerous Stage

Most tumours take many years to grow and form to the point where they produce clinical manifestations. Laryngeal cancer, for instance, appears only after several years of constant exposure to alcohol and tobacco smoke — a behaviour shared by many common tumours caused by environmental conditions. Careful studies of individuals with polyps of the colon (benign tumours of the inner lining of the large intestine) show that it takes three to five years for a new polyp to form and the same amount of time for the polyp to transform or progress into a carcinoma. Thus, when malignant tumours finally present with clinical manifestations, they are well into the last third of their life cycles.

In some instances it is known that certain abnormal cellular changes precede cancer. These alterations are collectively referred to as precancerous lesions. A number of terms, such as hyperplasia, dysplasia, and neoplasia, are used to describe precancerous lesions. For example, endometrial hyperplasia (increased cell growth in the endometrium, or inner lining of the uterus) often precedes, and may even set the stage for, cancer of the endometrium. Some clinical conditions are also known to be associated with an increased risk of carcinoma. Indeed, long-standing ulcerative colitis and leukoplakia of the oral cavity carry such an increase in risk that they are known as preneoplastic conditions for adenocarcinoma of the colon and squamous cell carcinoma of the mouth.

The Noninvasive Stage

Before tumours metastasize, or spread to other tissues of the body, they pass through a long period as noninvasive lesions. During this stage (the earliest stage in which cancer is recognized as such) the tumour remains in the anatomic site where it arose and does not invade beyond those confines. An example of such a lesion might be a carcinoma that has arisen from an epithelial cell lining the uterine cervix; as long as this carcinoma is confined to the mucosal lining and has not penetrated the basement membrane, which separates the lining from other tissue layers, it is known as a noninvasive tumour (or an in situ tumour). A tumour at this stage lacks its own network of blood vessels to supply nutrients and oxygen, and it has not sent cells into the circulatory system to give rise to new tumours. It also is usually asymptomatic — an unfortunate circumstance, because in situ tumours are curable.

Invasion and dissemination

In the next stage of tumour progression, a solid tumour invades nearby tissues by breaching the basement membrane. The basement membrane, or basal lamina, is a sheet of proteins and other substances to which epithelial cells adhere and that forms a barrier between tissues. Once tumours are able to break through this membrane, cancerous cells not only invade surrounding tissue substances but also enter the bloodstream — often via a lymphatic vessel, which discharges its contents into the blood. Tumour cells that have invaded a lymphatic vessel often become trapped in lymph nodes, whereas cells that gain access to blood vessels are disseminated to various parts of the body such as the bones, lungs, and brain. At such distant sites cancer cells form secondary tumours, or metastases. This ability to metastasize is what makes cancer such a lethal disease. The primary tumour (that is, the original tumour growing at the site of origin) can be controlled by many available therapies, but it is the disseminated disease that eventually proves fatal to the host.