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Cancer Biomarkers

Cancer Biomarkers Background


Cancer biomarkers are substances that can be found in the body when cancer is present. They are usually found in the blood or urine. They can be products of cancer cells or of the body in response to cancer. Most tumor markers are proteins. Tumor markers are playing an increasingly important role in cancer detection and management. These laboratory-based tests are potentially useful in screening for early malignancy, aiding cancer diagnosis, determining prognosis, surveillance following curative surgery for cancer, up front predicting drug response or resistance, and monitoring therapy in advanced disease. In asymptomatic subjects, tumor markers are potentially used in screening for early malignancy. In symptomatic patients, markers may help in the differential diagnosis of benign and malignant disease. Following diagnosis and surgical removal of a malignancy, markers may be used for assessing prognosis, postoperative surveillance, therapy prediction and monitoring response to systemic therapy. Irrespective of its application, an ideal tumor marker should exhibit the following characteristics:

• possess a high positive and negative predictive value;
• have an inexpensive, simple, standardized and automated assay with clearly defined reference limits;
• be acceptable to subjects undergoing the test;
• have its clinical value validated in a large prospective trial.

Use of Markers in Screening for Cancer

Screening involves the detection of early disease or a preclinical state in subjects without signs or symptoms of disease. Unlike disease diagnosis, screening is performed on individuals without any clinical sign of disease (Figure 1).

Table 1. Biomarkers that have undergone or are currently undergoing evaluation
in screening asymptomatic subjects for cancer

Marker or test Malignancy
FOBT
PSA
CA 125
VMA/HVA
AFP
Pepsinogen
HCG
Colorectal
Prostate
ovarian
neuroblastoma
hepatocellular1
gastric1
trophoblastic2
V MA = Vanillylmandelic acid; HVA = homovanillic acid.
1: Only in high-risk areas/high-risk subjects.
2: In patients who have had a previous hydatidiform mole

Use of Markers as Diagnostic Aids for Cancer

As discussed above with screening, limited sensitivity for small or early cancers and lack of tumor specificity preclude the use of serum markers for the primary diagnosis of cancer. In a limited number of situations, however, markers may aid in the differential of benign and malignant disease (Figure 2).

Table 2. Markers that may be used for determining prognosis in different cancers

Cancer Marker(s)
Breast
Germ cell
Colorectal
Prostate
Ovarian
Oncotype DX, uPA/PAI-1
AFP, HCG, LDH
CEA, MSI
PSA
CA 125
L DH = Lactate dehydrogenase; MSI = microsatellite instability.

Use of Markers in Assessing Prognosis

Prognostic markers provide information on the likely outcome following diagnosis of a disease. Such markers may help avoid under treatment of patients with aggressive disease and overtreatment of those with indolent disease. Prognostic markers are most important in cancers that vary widely in their outcome such as prostate and breast cancer. In these cancers, prognostic markers may help identify those patients with aggressive disease that could benefit from additional therapies and simultaneously select those patients who may not require additional therapy (Figure 3).

Table 3. Serum markers that may be used in postoperative surveillance and monitoring therapy in different cancers

Cancer Marker(s)
Colorectal
Hepatocellular
Pancreatic Ovarian
Breast
Prostate
Germ cell
Lung (non-small cell)
Lung (small cell)
Melanoma
Trophoblastic
Thyroid (differentiated)
CEA AFP
CA 19-9
CA 125
CA 15-3
PSA
AFP, HCG
CYFRA 21-1, SCC
NSE, proGRP
S100
HCG
thyroglobulin
S CC = Squamous cell carcinoma; NSE = neuron-specific enolase.


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