Serology is the science that deals with the characterization of serum, the noncellular component of blood. Serum contains many valuable proteins, nucleotides, and other chemicals that aid the physiological functions of the body. Between 1900 and 1950, numerous scientific studies were performed to study the production of serum and its use in monitoring and controlling diseases. This period has been called the era of International Serology.
Serological markers are used to distinguish specific diseases in individuals. These markers are invaluable in the detection of some cancers, especially due to their potential in identifying the early stages of the disease, prior to the onset of symptoms.
CRITERIA IN ASSESSING SEROLOGICAL MARKERS
Several criteria are used to assess a serological method in a clinical laboratory, including sensitivity, specificity, and predictive value. Diagnostic sensitivity (Se) is the ability to correctly identify those who have a specific disease and is defined by the ratio of true positives over true positives and false negatives. Diagnostic specificity (Sp) is the ability of the test to correctly identify those who do not have the disease and is defined by the ratio of true negatives over true negatives and false positives. Both of these indexes measure the accuracy of assays using serological markers relative to an established and standard procedure. The predictive value (Pr) contains two components: a positive predictive value (Pp) and a negative predictive value (Pn); the former describes the likelihood that a positive test result represents a true positive and the later defines the likelihood that a negative result is truly negative. All the above definitions are described in Figure 1.
EXAMPLES OF SEROLOGICAL MARKERS
Serologic markers have been studied extensively in immunology and have also been widely used in
the study, clinical diagnosis, and prognosis of cancer. Prostate-specific antigen (PSA) in serum has been studied widely and used in early detection and management of prostate cancer. Several monoclonal and polyclonal antibodies have been developed for the detection of PSA, and about 25 to 75 percent of patients with the disease have PSA in their sera. Even with the potential problem of lack of specificity of the test, PSA is the most widely used tumor-associated antigen.
The most commonly used markers for diagnosis and management of epithelial ovarian cancer is CA 125, which is an antigenic determinant, part of a glycoprotein present in the sera of approximately 80 percent of patients with epithelial ovarian cancer. It is found elevated in about 40 percent of patients with Stage I ovarian cancers and about 20 percent of patients with mucinous malignancies. In addition, approximately 60 percent of pancreatic carcinomas express CA 125, as do 25 percent of all other solid tumors. However, CA 125 is not only a marker for cancer, but is also elevated in a number of benign gynecologic conditions, including pelvic inflammatory disease, endometriosis, uterine leiomyoma, and early pregnancy. This nonspecificity has limited the use of CA 125 as a tumor maker in screening and diagnosis.
Carcinoembryonic antigen (CEA), alphafetoprotein (AFP), and altered carbohydrate antigen 19–9 (CA19–9) have been studied in the past decade for early diagnosis of human pancreatic adenocarcinoma and gastrointestinal malignancies. The utility of CEA as a serum marker in the detection of tumors has been limited due to the finding that CEA levels are affected by a variety of factors, including liver function, biliary obstruction, and subclinical hepatitis, and because the interlaboratory variation in CEA measurements could run as high as 36 percent.
AFP was first described as a tumor marker for hepatoma in the 1960s. It is most frequently elevated among patients with hepatoma and yolk sac (endodermal sinus) tumors. AFP-positive tumors can be found throughout the gastrointestinal tract.
CA 19–9 is frequently elevated in pancreatic cancer, but is also elevated in cancers of the biliary tract, and less frequently in colorectal and gastric cancers. Studies have shown that CA 19–9 can identify, with reasonable accuracy, the majority of patients with pancreatic cancer in a highly select patient population. The utility of other markers, such as pancreatic oncofetal antigen (POA) and tumor-associated trypsin inhibitor (TATI), is still being studied.
Serological markers have great potential to be used in clinical practice, including early detection of cancer, because these markers are differently expressed—qualitatively or quantitatively, and because they vary between either people who are healthy and those that have certain diseases. However, sensitivity and specificity issues remain the critical challenge when developing new serum markers for diagnostic and prognostic purposes. Technological advancements, standardization of the tests, and acceptance by the medical community are required to allow widespread applications of serological markers in medicine.
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