Porth's Essentials of Pathophysiology, 4e

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Cell and Tissue Function

U N I T 1

The serum markers that have proven most useful in clinical practice are the human chorionic gonadotro- pin (hCG), prostate-specific antigen (PSA), CA-125, α -fetoprotein (AFP), CD blood cell antigens, and car- cinoembryonic antigen (CEA). The hCG is a hormone normally produced by the placenta. It is used as a marker for diagnosing, prescribing treatment, and following the disease course in persons with high-risk gestational trophoblastic tumors. Prostate-specific antigen (PSA) is used as a marker in prostate cancer, and CA-125 is used as a marker in ovarian cancer. Markers for leuke- mia and lymphomas are grouped by so-called clusters of differentiation (CD) antigens (see Chapter 15). The CD antigens help to distinguish among T and B lympho- cytes, monocytes, granulocytes, and natural killer cells and immature variants of these cells. 2,3 Some cancers express fetal antigens that are nor- mally present only during embryonal development and induced to reappear as a result of neoplasia. 2 The two that have proved most useful as tumor markers are alpha fetoprotein (AFP) and CEA. α -fetoprotein is synthesized by the fetal liver, yolk sac, and gastrointestinal tract and is the major serum protein in the fetus. Elevated levels are encountered in people with primary liver cancers and have also been observed in some testicular, ovarian, pancreatic, and stomach cancers. Carcinoembryonic antigen normally is produced by embryonic tissue in the gut, pancreas, and liver and is elaborated by a number of different cancers, including colorectal carcinomas, pancreatic cancers, and gastric and breast tumors. As with most other tumor markers, elevated levels of AFP and CEA are found in other, noncancerous conditions, and elevated levels of both depend on tumor size so that neither is useful as an early test for cancer. As diagnostic tools, tumor markers have limitations. Nearly all markers can be elevated in benign conditions, andmost are not elevated in the early stages of malignancy. Furthermore, they are not in themselves specific enough to permit a diagnosis of a malignancy, but once a malig- nancy has been diagnosed and shown to be associated with elevated levels of a tumor marker, the marker can be used to assess progress of the disease. Extremely elevated levels of a tumor marker can indicate a poor prognosis or the need for more aggressive treatment. Perhaps the great- est value of tumor markers is in monitoring therapy in people with widespread cancer. The level of most cancer markers tends to decrease with successful treatment and increase with recurrence or spread of the tumor. Cytologic, Histologic, and Gene-Profiling Methods Cytologic and histologic studies are laboratory meth- ods used to examine tissues and cells. Several sampling approaches are available including cytologic smears, tis- sue biopsies, and needle aspiration. 2 Papanicolaou Smear. The Pap smear is a cytologic method that consists of a microscopic examination of a properly prepared slide by a cytotechnologist or patho­ logist for the purpose of detecting the presence of abnor-

mal cells. The usefulness of the Pap smear relies on the fact that cancer cells lack the cohesive properties and intercellular junctions that are characteristic of normal tissue; without these characteristics, cancer cells tend to exfoliate and become mixed with secretions surround- ing the tumor growth. Although the Pap smear is widely used as a screening test for cervical cancer, it can be per- formed on other body secretions, including nipple drain- age, pleural or peritoneal fluid, and gastric washings. Tissue Biopsy. Tissue biopsy involves the removal of a tissue specimen for microscopic study. It is of criti- cal importance in designing the treatment plan should cancer cells be found. Biopsies are obtained in a number of ways, including needle biopsy; endoscopic methods, such as bronchoscopy or cystoscopy, which involve the passage of an endoscope through an orifice and into the involved structure; and laparoscopic methods. Fine needle aspiration involves withdrawing cells and attendant fluid with a small-bore needle. The method is most widely used for assessment of readily palpable lesions in sites such as the thyroid, breast, and lymph nodes. Modern imaging techniques have also enabled the method to be extended to deeper structures such as the pelvic lymph nodes and pancreas. In some instances, a surgical incision is made from which biopsy specimens are obtained. Excisional biop- sies are those in which the entire tumor is removed. The tumors usually are small, solid, palpable masses. If the tumor is too large to be completely removed, a wedge of tissue from the mass can be excised for examination. A quick frozen section may be done and examined by a pathologist to determine the nature of a mass lesion or evaluate the margins of an excised tumor to ascertain that the entire neoplasm has been removed. 3 Immunohistochemistry. Immunohistochemistry inv­ olves the use of monoclonal antibodies to facilitate the identification of cell products or surface markers. 3 For example, certain anaplastic carcinomas, malignant lymphomas, melanomas, and sarcomas look very simi- lar under the microscope, but must be accurately iden- tified because their treatment and prognosis are quite different. Immunohistochemistry can also be used to determine the site of origin of metastatic tumors. Many cancer patients present with metastasis. In cases in which the ori- gin of the metastasis is obscure, immunochemical detec- tion of tissue-specific or organ-specific antigens can often help to identify the tumor source. Immunochemistry can also be used to detect molecules that have prognostic or therapeutic significance. For example, detection of estro- gen receptors on breast cancer cells is of prognostic and therapeutic significance because these tumors respond to antiestrogen therapy. Microarray Technology. Microarray technology has the advantage of analyzing a large number of molecu- lar changes in cancer cells to determine overall patterns of behavior that would not be available by conventional means. The technique uses “gene chips” that can perform