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Tumor markers tests (cancer biomarkers)

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Tumor Markers Overview

Cancer remains a major global health challenge, being a leading cause of mortality after cardiovascular and cerebrovascular diseases. While advances in prevention and treatment are ongoing, early diagnosis is critical for improving outcomes. Unfortunately, many cancers are detected at later stages when they have already spread (generalized or metastasized), making successful treatment more difficult.

Detecting malignant tumors in their early stages significantly increases the likelihood of successful treatment, potentially leading to cure in up to 90% of cases. In oncology, laboratory tests that measure specific substances known as tumor markers (or cancer biomarkers) play an important role alongside imaging and pathology in the management of cancer patients.

These markers can aid in screening high-risk individuals, supporting diagnosis, determining prognosis, monitoring treatment effectiveness, and detecting cancer recurrence or metastasis earlier than might be possible with imaging or clinical symptoms alone.

Tumour markers serve as indispensable tools in the realm of cancer detection and diagnosis, offering valuable insights into disease progression and treatment response.

What are Tumor Markers?

The terms "tumor markers" or "cancer biomarkers" encompass a broad and diverse group of biological substances that are produced either by cancer cells themselves or by the body in response to cancer. Their presence, or changes in their levels, can be correlated with the existence or progression of a malignant process.

These markers can have various biochemical characteristics, including:

  • Oncofetal Antigens: Proteins normally produced during fetal development but re-expressed by some cancer cells (e.g., AFP, CEA).
  • Oncoplacental Antigens: Proteins normally produced by the placenta (e.g., hCG).
  • Tumor-Associated Antigens: Often glycoproteins or mucins overexpressed or altered on the surface of cancer cells (e.g., CA 15-3, CA 125, CA 19-9, MCA).
  • Enzymes: Isoenzymes produced in higher amounts by certain tumors (e.g., NSE, LDH, PSA - prostatic acid phosphatase less used now).
  • Hormones: Produced ectopically by non-endocrine tumors or excessively by endocrine tumors (e.g., Calcitonin in MTC, hCG).
  • Oncogene Products or Related Proteins: Proteins related to cancer-causing genes (e.g., HER2 in tissue).
  • Plasma Proteins: Specific proteins whose levels change significantly (e.g., Beta-2 Microglobulin in myeloma/lymphoma).
  • Metabolic Products.
  • Bioactive Peptides.
  • Genetic Markers: Mutations or alterations in DNA/RNA found in tumor tissue or circulating in blood (liquid biopsy) - an expanding area.

These markers are typically measured in blood (serum or plasma), urine, or tumor tissue itself.

Clinical Uses of Tumor Markers

Tumor markers have several potential applications in oncology, although their utility varies greatly depending on the specific marker and cancer type:

  • Screening: Detecting cancer in asymptomatic individuals. Only a few markers are suitable for screening specific high-risk populations (e.g., PSA for prostate cancer - controversial, AFP for HCC in cirrhosis patients, low-dose CT for lung cancer screening - not a blood marker). Most markers lack the specificity needed for general population screening.
  • Diagnosis: Helping to establish a diagnosis, often in conjunction with imaging and biopsy. Few markers are diagnostic on their own, but some (like very high AFP/hCG for GCTs, high Calcitonin for MTC) can be highly suggestive. They can sometimes aid in differential diagnosis when the primary tumor site is unknown (e.g., NSE suggests neuroendocrine origin).
  • Staging & Prognosis: The level of a tumor marker at diagnosis can sometimes correlate with the stage (extent) of the cancer and provide prognostic information (predicting likely outcome or aggressiveness).
  • Monitoring Treatment Effectiveness: A significant decrease in an elevated marker level after treatment (surgery, chemotherapy, radiation) typically indicates a positive response. Failure to decline or subsequent increases suggest treatment resistance or failure.
  • Detecting Recurrence: A rise in tumor marker levels during follow-up after initial remission can be the earliest sign of cancer recurrence or metastasis, often preceding clinical symptoms or imaging findings. This allows for earlier initiation of salvage therapy.

Characteristics of an Ideal Tumor Marker

The "ideal" tumor marker would possess several key characteristics, though no current marker meets all these criteria perfectly:

  • High Specificity: Found only in patients with a specific type of cancer and not in healthy individuals or those with benign diseases (minimizing false positives).
  • High Sensitivity: Detectable even when the tumor is very small (early stage) and present in almost all patients with that cancer (minimizing false negatives).
  • Organ Specificity: Produced only by the tumor originating in a specific organ.
  • Correlation with Tumor Burden: Levels should directly correlate with the amount of cancer present (tumor size, stage).
  • Correlation with Treatment Response: Levels should accurately reflect the success or failure of treatment.
  • Prognostic Value: Levels should help predict the likely course and outcome of the disease.
  • Predictive Value: Levels might help predict whether a patient will respond to a specific therapy.
  • Easy and Reliable Measurement: Test should be reproducible, readily available, and relatively inexpensive.

Limitations and Considerations

It is crucial to understand the limitations when using tumor markers:

  • Lack of Specificity: Many tumor markers can be elevated in benign (non-cancerous) conditions (e.g., inflammation, infection, liver or kidney disease), leading to false-positive results and unnecessary anxiety or further testing.
  • Lack of Sensitivity: Not all cancers of a specific type produce the associated marker, and levels may not be elevated in early-stage disease, leading to false-negative results. A normal tumor marker level does not rule out cancer or recurrence.
  • Lead-Time Bias: Detecting recurrence earlier with a marker might not always translate into improved survival if effective salvage therapy is not available.
  • Heterogeneity: Tumors can be diverse, and not all cells within a tumor may produce the marker consistently.
  • Combination Testing: Due to the limitations of single markers, using a panel of several different markers is sometimes employed to improve sensitivity or specificity for certain cancers (e.g., AFP + hCG for germ cell tumors).

Therefore, tumor marker results must always be interpreted in the context of the patient's overall clinical picture, including history, physical examination, imaging studies, and pathology results.

Tumor Markers in Monitoring

One of the most valuable applications of tumor markers is in monitoring patients already diagnosed with cancer.

  • Baseline Level: Establishing a baseline level before starting treatment is important.
  • Post-Treatment Decline: The rate at which a marker level decreases after surgery or during chemo/radiotherapy can indicate treatment effectiveness and predict prognosis. The time it takes for the marker to return to normal (its half-life) is relevant.
  • Surveillance for Recurrence: Serial measurements during follow-up can detect a rise in marker levels, often signalling recurrence before it becomes clinically apparent. This requires consistent testing intervals and careful interpretation of trends rather than single values.
  • Reliability for Action: Ideally, a rising marker indicative of relapse should be reliable enough to prompt further investigation (e.g., imaging) or even treatment decisions, sometimes even before definitive radiological or cytological confirmation (though this depends heavily on the specific marker and clinical context).

Examples of Common Tumor Markers

Below are links to brief descriptions of some tumor markers commonly used in clinical practice:

How Tumor Marker Tests are Performed

  • Sample Type: Most commonly blood (serum or plasma). Can also be urine, other body fluids (like CSF, pleural fluid), or tumor tissue itself (e.g., for hormone receptors, HER2, genetic mutations).
  • Preparation: Usually no special preparation (like fasting) is needed for most blood-based tumor marker tests. Follow specific instructions from your doctor or the laboratory.
  • Collection: Standard venipuncture (blood draw), urine collection, or biopsy procedure.
  • Analysis: Performed in a clinical laboratory using various techniques, most often immunoassays (like ELISA, CLIA) that use antibodies to detect and quantify the marker.

References

  1. National Cancer Institute (NCI). (n.d.). Tumor Markers. Retrieved from https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet
  2. American Cancer Society (ACS). (2023). Tumor Markers. Retrieved from https://www.cancer.org/cancer/diagnosis-staging/tests/tumor-markers.html
  3. Mayo Clinic Staff. (n.d.). Tumor markers: Used to help diagnose cancer. Mayo Clinic Patient Care & Health Information. Retrieved from https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/tumor-markers/art-20045438
  4. Sturgeon, C. M., Hoffman, B. R., Chan, D. W., Ch'ng, S. L., Hammond, E., Hayes, D. F., ... & Diamandis, E. P. (2008). National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in clinical practice: quality requirements. *Clinical Chemistry*, 54(8), e1–e10. https://doi.org/10.1373/clinchem.2007.094144
  5. Duffy, M. J. (2007). Role of tumor markers in patients with solid cancers: A critical review. *European Journal of Internal Medicine*, 18(3), 175–184. https://doi.org/10.1016/j.ejim.2006.12.001
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