The underlying cause of cancer can be divided into four major classifications: viral, chemical, physical, and genetic. Cancers caused by viruses can be either RNA viruses (e.g., retrovirus HTLV-I, which causes ATL) or DNA viruses (e.g., HBV, which causes hepatocellular carcinoma). Chemical carcinogens can be classified as either genotoxic (targeting the DNA [e.g., nitroso compounds that when heated release toxic fumes or solvents such as trichloroethylene]) or nongenotoxic (targeting cell death directly or hormonal effects [e.g., synthetic pesticides or herbicides]). Physical factors associated with causing cancer include ultraviolet light (sunlight), ionizing radiation (x-rays), and asbestos fibers. Hereditary or genetic cancer can account for up to 30% of some forms of childhood cancers and 5%–10% of adult cancers.

Cancerous cells differ from normal cells in many respects. Malignant cells grow more rapidly in an uncontrolled fashion and lack normal cell-to-cell interactions, and apoptotic (programmed cell death) mechanisms are disrupted when compared with normal cells. Normal cells, through a series of mutations (referred to as hits) and alterations of normal cell growth and cell interactions, can transition into cancerous cells. This unregulated and disorganized increase in cell growth is stimulated by the factors described earlier. Tumors, by definition, are spontaneous growth of abnormal cells leading to a swelling or enlargement of the underlying tissue. This abnormal cell growth, or cancer, can be detected by certain substances (tumor markers) found in the blood.

There are a number of factors that have either a protective effect or promote cancer growth.

Tumor markers include genetic markers (abnormal chromosomes or oncogenes), DNA analysis, oncofetal antigens, enzymes, hormones, placental proteins, steroid receptors, glucoproteins, tumor-associated antigens, tumor-specific antigens, and circulating immune complexes.

Tumor cells differ from normal cells in many ways. Physical examination and standard x-ray techniques can usually detect tumors as small as 1 cm in volume. A tumor mass of this size has completed 30 doublings (two thirds of its growth) and contains 1 billion (10⁻⁹) cells. Certain tumor antigens, hormones, oncofetal proteins, and enzymes are secreted into the bloodstream by these tumors.

Malignant tumor cells are produced when DNA is damaged by some form of carcinogen, virus, radiation, or chemical causing the process of mitosis to go out of control. These growing, changed (mutant) cells express oncogenes. These oncogenes are capable of inducing or transforming cells into cancer cells or tumors. Tumor cells capable of forming metastases are likely to invade blood vessel walls; be released into the bloodstream, regional lymphatics, or interstitial stroma; and eventually spread to other organs. Tumor testing has focused on identifying certain tumor-related substances that might allow early detection of malignancy, determination of prognosis, and evaluation of tumor burden (i.e., size, location, and encroachment on other tissues or organs).

Tumor markers are used and developed to obtain greater sensitivity and specificity in determining the presence of cancer and tumor activity. These substances are found in body cells, fluids, and tissue. In general, these markers lack specificity for cancer; none is pathognomonic for any one type of neoplasm. Tumor marker studies do not replace biopsy and pathologic tissue examination and are not ideal for screening for specific cancers, making a diagnosis, or predicting programs for symptomatic patients, but they are effective for tumor staging, monitoring response to therapy, detecting disease recurrence, and early detection of cancer recurrence. Diagnosis still derives from a biopsy and tissue examination, comprehensive patient history, physical examination, and other diagnostic procedures.

The following are diagnostic, prognostic, and predictive markers:

1. Oncofetal antigens, normally produced in the fetus, are reactivated with cancer cell transformation:

   1. Carcinoembryonic antigen

   2. Alpha-fetoprotein

   3. Proteins:

      1. CA 125

      2. CA 19-9

      3. CA 15-3

      4. CA 549

   4. Tissue polypeptide antigen

   5. Prostate-specific antigen

   6. hK2 and hK3 of gene family = kallikreins

   7. Human glandular kallikrein for prostate cancer

2. Placental proteins:

   1. Human chorionic gonadotropin (hCG and beta-hCG)

   2. Human placental lactogen

   3. Placental alkaline phosphatase

3. Enzymes and isoenzymes:

   1. Prostatic acid phosphatase

   2. Creatine kinase–BB isoenzyme

   3. Alkaline phosphatase

   4. Neuron-specific enolase

   5. Lactate dehydrogenase isoenzyme

   6. Lysozyme (muramidase)

4. Hormones:

   1. Hormones, both normally produced by the tissue and ectopic

   2. Gamma-glutamyl transpeptidase (GGT)

   3. Luteinizing hormone

   4. Amylase

   5. Terminal deoxynucleotidyl transferase

   6. hCG—trophoblastic tumors

   7. Nonseminomatous testicular tumors

   8. Hydroxyindoleacetic acid

   9. Epinephrine and norepinephrine—pheochromocytoma and related malignancies

   10. 17-Ketosteroids

   11. Gastrin-Zollinger-Ellison syndrome (gastrinoma)

   12. Renin—produced by kidney

   13. Calcitonin–medullary carcinoma of the thyroid (not normally produced by the tissue)

   14. Adrenocorticotropic hormone—small cell carcinoma of the lung

   15. Antidiuretic hormone

   16. Parathyroid-related peptide

   17. Erythropoietin

   18. Gastrin

5. (Serotonin) immunoglobulins:

   1. IgG

   2. IgA

   3. IgM

   4. IgD

   5. IgE

   6. Kappa and lambda light chains

6. Steroid receptors:

   1. Estrogen and progesterone receptors

   2. Epidermal growth factor receptor

   3. HER-2 (human epidermal growth factor receptors)

   4. Androgen receptors

   5. Corticosteroid receptors

7. Immunocomplex typing:

   1. Lymphoid cells

   2. Myeloid cells

   3. Cytokines

8. DNA analysis:

   1. Ploidy and S-phase fraction

   2. See Chapter 11 for more information

9. Molecular diagnosis

   1. Oncogene and suppressor genes

   2. Genetic changes

   3. See Chapter 11 for more information

See Table 8.12 for the value for each specific tumor marker.

1. Be aware that most tumor marker tests involve obtaining either venous plasma or serum, urine or bladder washings, or CSF; some may require fasting.

2. Follow the specific directions from the laboratory or cancer center involved in the testing procedure. Be sure to note factors that interfere with test results.

1. Tumor markers, substances produced and secreted by tumor cells and found in serum, urine, or tissue of persons with cancer, are indicative of tumor activity.

2. Table 8.13 includes types of cytokines, their origin and target cells, and clinical implications.

Pretest Patient Care

1. Explain purpose and procedure of test.

2. Alleviate fears the patient may have related to cancer test results. Tests for cancer are always anxiety provoking.

3. Follow guidelines in Chapter 1 for safe, effective, informed pretest care.