Tumor markers applications

The premarket notification application, 510(k), is reviewed by the FDA scientific staff. This evaluation takes into consideration tumor-associated analytes, test requirements, medical usefulness of the test system for a particular clinical claim, and its application (i.e., monitoring or treatment follow-up). The FDA determines the appropriate performance requirements for each tumor analyte category. The agency s staff considers factors, such as consequences of a false positive or false negative, and the importance or impact of an absolute versus a significant change in the results or values of the tumor marker tests. The performance criteria (parameters) of a particular tumor marker test are compared with those of previously... 

The establishment of performance criteria for a given tumor marker test is not a simple process because accuracy and precision are unique for each type of analyte and its application. Establishing methodological limits for accuracy, precision, sensitivity, and specificity often requires standard reference materials, quality control materials, comparative studies, and actual clinical specimens. Accuracy and precision must be measured over the analyte reportable range for which the device is intended to be used. Sensitivity and specificity must be considered with respect to the intended clinical use of the device. Also, the indications for use should be carefully considered in the design of the study protocol. The indications for class II should be to monitor residual tumor after surgery (or radiation), the recurrence of tumor, or response to therapy. A 510(k) must provide clear evidence that the device is accurate, safe, effective, and substantially equivalent to a device legally marketed in the United States. 

Aziz, K. J. Tumor markers Current status and future applications. Scand Clin. Lab. Invest. 55, 153-155(1995). 

Listed in Table 22.1 are different tumor markers for certain types of cancer, with their primary applications and the techniques related with their discovery process. Among them the alpha 1 fetoprotein and CEA are the most frequently exploited. 

Tumor marker cancer site application year Positives... 

Bates SE, Clinical application of serum tumor markers, Ann. Intern. Med., 115 623-638, 1991. 

In addition, antibodies to tumor markers labeled with a radioactive tag are used to localize the tumor masses (radioimmunoscintigraphy) or to provide direction for labeled antibodies to attack the tumor site. Examples are the use of radiolabeled antibodies to CEA to localize colon tumors and the application of labeled antibodies against ferritin to target hepatocellular carcinoma. This approach is... 

TABLE 23-3 Current Applications of Tumor Markers and Their Limitations—Continued... 

Modified from Diamandis EP. Tumor markers Past, present, and future. In Diamandis EP, Fritsche HA, Lilja H, Chan DW, Schwartz MK. Tumor markers Physiology, pathobiology, technology, and clinical application. Washington DC AACC Press, 2002 5. 

With few exceptions, an increase in the activity or mass of an enzyme or isoenzyme is not specific or sensitive enough to be used for identifying the type of cancer or the specific organ involvement. An exception is PSA. PSA has mild protease activity and amino acid sequence homology with serine protease of the kallikrein family.It is expressed by normal, benign, hyperplastic, and cancerous prostate glands and minimally by other tissue. Until the application of PSA as a marker for prostate cancer, tumor enzymes had lost most of their popularity for use as cancer markers. Enzymes were used historically as tumor markers before the discovery of oncofetal antigens and the advent of monoclonal antibodies. The abnormalities of enzymes as a marker for cancer are either the expression of the fetal form of the enzyme (isozyme) or the ectopic production of enzymes. 

Although helpful in surveillance of patients with diagnosed ovarian cancer, the tumor marker CA-125 does not improve early detection of ovarian cancer when used alone [5]. Investigations examining genomic and pro-teomic patterns as possible complementary biomarkers for early ovarian cancer have shown some promise. However, further study is necessary to ascertain whether these biomarkers provide sufficient improvement in diagnostic accuracy to justify their more widespread application for ovarian cancer screening [19]. 

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