NURS 530 Discussion the process by which cancer originates

NURS 530 Discussion the process by which cancer originates

NURS 530 Discussion the process by which cancer originates

The fundamental abnormality resulting in the development of cancer is the continual unregulated proliferation of cancer cells. Rather than responding appropriately to the signals that control normal cell behavior, cancer cells grow and divide in an uncontrolled manner, invading normal tissues and organs and eventually spreading throughout the body. The generalized loss of growth control exhibited by cancer cells is the net result of accumulated abnormalities in multiple cell regulatory systems and is reflected in several aspects of cell behavior that distinguish cancer cells from their normal counterparts.

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Types of Cancer

Cancer can result from abnormal proliferation of any of the different kinds of cells in the body, so there are more than a hundred distinct types of cancer, which can vary substantially in their behavior and response to treatment. The most important issue in cancer pathology is the distinction between benign and malignant tumors (Figure 15.1). A tumor is any abnormal proliferation of cells, which may be either benign or malignant. A benign tumor, such as a common skin wart, remains confined to its original location, neither invading surrounding normal tissue nor spreading to distant body sites. A malignant tumor, however, is capable of both invading surrounding normal tissue and spreading throughout the body via the circulatory or lymphatic systems (metastasis). Only malignant tumors are properly referred to as cancers, and it is their ability to invade and metastasize that makes cancer so dangerous. Whereas benign tumors can usually be removed surgically, the spread of malignant tumors to distant body sites frequently makes them resistant to such localized treatment.

Figure 15.1

A malignant tumor of the uterus. Micrographs of normal uterus (A) and a section of a uterine sarcoma (B). Note that the cancer cells (darkly stained) have invaded the surrounding normal tissue. (Cecil Fox/Molecular Histology, Inc.)

Both benign and malignant tumors are classified according to the type of cell from which they arise. Most cancers fall into one of three main groups: carcinomas, sarcomas, and leukemias or lymphomas. Carcinomas, which include approximately 90% of human cancers, are malignancies of epithelial cells. Sarcomas, which are rare in humans, are solid tumors of connective tissues, such as muscle, bone, cartilage, and fibrous tissue. Leukemias and lymphomas, which account for approximately 8% of human malignancies, arise from the blood-forming cells and from cells of the immune system, respectively. Tumors are further classified according to tissue of origin (e.g., lung or breast carcinomas) and the type of cell involved. For example, fibrosarcomas arise from fibroblasts, and erythroid leukemias from precursors of erythrocytes (red blood cells).

Although there are many kinds of cancer, only a few occur frequently (Table 15.1). More than a million cases of cancer are diagnosed annually in the United States, and more than 500,000 Americans die of cancer each year. Cancers of 10 different body sites account for more than 75% of this total cancer incidence. The four most common cancers, accounting for more than half of all cancer cases, are those of the breast, prostate, lung, and colon/rectum. Lung cancer, by far the most lethal, is responsible for nearly 30% of all cancer deaths.

Table 15.1

Ten Most Frequent Cancers in the United States.

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The Development of Cancer

One of the fundamental features of cancer is tumor clonality, the development of tumors from single cells that begin to proliferate abnormally. The single-cell origin of many tumors has been demonstrated by analysis of X chromosome inactivation (Figure 15.2). As discussed in Chapter 8, one member of the X chromosome pair is inactivated by being converted to heterochromatin in female cells. X inactivation occurs randomly during embryonic development, so one X chromosome is inactivated in some cells, while the other X chromosome is inactivated in other cells. Thus, if a female is heterozygous for an X chromosome gene, different alleles will be expressed in different cells. Normal tissues are composed of mixtures of cells with different inactive X chromosomes, so expression of both alleles is detected in normal tissues of heterozygous females. In contrast, tumor tissues generally express only one allele of a heterozygous X chromosome gene. The implication is that all of the cells constituting such a tumor were derived from a single cell of origin, in which the pattern of X inactivation was fixed before the tumor began to develop.

Figure 15.2

Tumor clonality. Normal tissue is a mosaic of cells in which different X chromosomes (X₁ and X₂) have been inactivated. Tumors develop from a single initially altered cell, so each tumor cell displays the same pattern of X inactivation (X₁ inactive, X (more…)

The clonal origin of tumors does not, however, imply that the original progenitor cell that gives rise to a tumor has initially acquired all of the characteristics of a cancer cell. On the contrary, the development of cancer is a multistep process in which cells gradually become malignant through a progressive series of alterations. One indication of the multistep development of cancer is that most cancers develop late in life. The incidence of colon cancer, for example, increases more than tenfold between the ages of 30 and 50, and another tenfold between 50 and 70 (Figure 15.3). Such a dramatic increase of cancer incidence with age suggests that most cancers develop as a consequence of multiple abnormalities, which accumulate over periods of many years.