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Cancer Characteristics and Terminology
- Benign tumors are usually encapsulated, well differentiated, and do not spread to distant locations.
- Malignant tumors, compared to benign tumors, have more rapid growth rates, specific microscopic alterations (anaplasia and loss of differentiation), absence of normal tissue organization, and no capsule; they invade into blood vessels and lymphatics and have distant spread.
- Carcinomas arise from epithelial tissue, sarcomas arise from connective tissue, lymphomas arise from lymphatic tissue, and leukemias are cancers of blood-forming cells. Carcinoma in situ (CIS) refers to preinvasive epithelial tumors of glandular or squamous cell origin.
- Localized cancer is considered low stage, whereas cancers that have spread regionally or distantly are termed stage 3 and stage 4 respectively.
- Cancer cells are characterized by anaplasia, or loss of differentiation, and autonomy, or independence from normal cellular controls.
- Tumor markers are substances (i.e., hormones, enzymes, genes, antigens, and antibodies) found in blood, spinal fluid, or urine. They are used to screen and identify individuals at high risk for cancer, to help diagnose specific types of tumors, and to follow the clinical course of cancer.
- In the adult, undifferentiated cells (not totally committed to a specific function) are known as pluripotent cells, precursor cells, or stem cells. Cancer cells become more like embryonic cells and are less differentiated. Cancerous growth depends on derangements of cell differentiation.
The Genetic Basis of Cancer
- Three main genetic mechanisms have a role in human carcinogenesis: (a) mutation of genes resulting in hyperactivity of growth-related gene products (such genes are called oncogenes); (b) mutation of genes resulting in loss or inactivity of gene products that normally would inhibit growth (such genes are called tumor suppressor genes); and (c) mutation of genes resulting in overexpression of products that prevent normal cell death, or apoptosis, thus allowing continued growth of tumors.
- Genetic events are the primary basis of carcinogenesis. Mutations in cancer-causing genes accumulate with age, causing the increasing risk of cancer with advanced age.
- Epidemiologic and molecular data suggest it takes five or six distinct mutations in different signaling pathways to produce cancer. Mutations activate growth-promotion pathways, block antigrowth signals, prevent apoptosis, turn on telomerase and new blood vessel growth (angiogenesis), and allow tissue invasion and distant metastasis.
- In rare families, cancer is inherited in an autosomal dominant fashion as a result of mutations in tumor suppressor genes.
- Proto-oncogenes encode for growth factors, growth-factor receptors, signal transducers, and nuclear growth-promoting proteins.
- Tumor suppressor genes encode for proteins that act as inhibitors of growth. Tumor suppressor gene proteins block specific phases of the cell cycle, induce end-stage (e.g., terminal) differentiation, and stimulates cell senescence or death. Carcinogenesis, or the development of cancer, involves inactivation of tumor suppressor genes (usually by loss of heterozygosity, or by “silencing”) and activation of oncogenes.
Infection, Immunity, Inflammation, and Cancer
- A number of viruses can cause cancer. Human cervical cancer is caused by papollomavirus infection. Kaposi sarcoma is caused by infection with a member of the herpesvirus family. Chronic hepatitis B or C infection can cause liver cancer.
- Immune system defects, such as those caused by immunosuppressant drugs or HIV infection, increase the risk of viral-associated cancers, such as EBV-associated lymphomas and cervical cancer.
- Chronic inflammation contributes to the development of cancer by stimulating increased proliferation and angiogenesis. Chronic hepatitis and colitis are two examples where chronic inflammation markedly increases the risk of cancer.
Cancer Progression and Metastasis
- Cancers metastasize through veins and lymphatics, first regionally and then distantly. Most cancer cells are not capable of successful metastasis; however, when metastasis does occur, it often portends a poor prognosis.
- Most cancer cells are not capable of successful metastasis. Multiple steps, including invasion, survival in the circulation, attachment, and growth, and induction of angiogenesis at a favorable distant site are required. Thus, both the seed and the soil must be matched for metastasis to occur.