Cancer Testing: Tumor Markers Explained

Exploring the Types of Serum Tumor Marker Tests Available in Medical Laboratories

Serum tumor markers are essential tools in modern oncology (the science of cancer), aiding in the diagnosis, prognosis, treatment monitoring, and recurrence detection of various cancers. These markers are substances, often proteins, that can be detected in the blood and are produced either by cancer cells or by the body in response to the presence of cancer.

Let's think about this: All cancers are uncontrolled growth of a certain type of cell. So, if that type of cell produces a certain, specific molecule, it can be used as a tumor marker for that type of tumor. Thus, they are indirect measurements of the presence of cancers or how tumors are growing or how aggressive they are.

Medical laboratories offer a range of serum tumor marker tests, each suited to specific cancer types and clinical needs. Below, we delve into the various types of serum tumor markers available and their applications in clinical practice.

Prostate-Specific Antigen (PSA)

Prostate-specific antigen (PSA) is one of the most widely recognized and utilized serum tumor markers. It is primarily used for:

• Screening and Early Detection: Elevated PSA levels can indicate prostate cancer, although benign conditions such as benign prostatic hyperplasia (BPH) and prostatitis can also cause increased levels.

• Monitoring Treatment: PSA levels are tracked over time to evaluate the effectiveness of treatments such as surgery or radiation therapy.

• Recurrence Detection: Rising PSA levels post-treatment may signal cancer recurrence.

  
  

PSA testing has become a cornerstone in prostate cancer management, though its use for routine screening remains a topic of ongoing debate due to the risk of overdiagnosis.

Carcinoembryonic Antigen (CEA)

Carcinoembryonic antigen (CEA) is another commonly used serum tumor marker. It is most often associated with colorectal cancer but can also be elevated in other malignancies, including lung, breast, and pancreatic cancers. Applications of CEA testing include:

• Diagnosis and Staging: While not highly specific, elevated CEA levels in conjunction with imaging can support a cancer diagnosis.

• Monitoring Therapy: Serial CEA measurements help assess response to treatment.

• Recurrence Monitoring: Rising CEA levels after treatment may indicate cancer recurrence before it becomes detectable through imaging.

  
  

However, elevated CEA levels can also occur in benign conditions like smoking and inflammatory diseases, so results must be interpreted carefully.

Alpha-Fetoprotein (AFP)

Alpha-fetoprotein (AFP) is a key tumor marker for certain cancers, particularly:

• Hepatocellular Carcinoma (HCC): AFP is often elevated in liver cancer and can be used for both diagnosis and monitoring.

• Germ Cell Tumors: AFP is useful in diagnosing and tracking non-seminomatous germ cell tumors of the testes and ovaries.

  
  

In addition to its role in cancer, AFP testing is also utilized in prenatal screening for fetal abnormalities.

Cancer Antigen 125 (CA-125)

CA-125 is primarily associated with ovarian cancer and is used in the following ways:

• Diagnosis: Elevated CA-125 levels can support the diagnosis of ovarian cancer, particularly in postmenopausal women with suspicious pelvic masses.

• Monitoring Treatment: Changes in CA-125 levels during and after treatment can indicate response to therapy.

• Recurrence Detection: Rising levels may signal the recurrence of ovarian cancer.

  
  

While CA-125 is a valuable tool, it is not specific to ovarian cancer and can be elevated in conditions such as endometriosis, fibroids, and pelvic inflammatory disease.

Cancer Antigen 19-9 (CA 19-9)

CA 19-9 is primarily associated with pancreatic cancer but may also be elevated in bile duct, gallbladder, and gastric cancers. Its applications include:

• Diagnosis: While not specific enough for early detection, CA 19-9 can support the diagnosis of pancreatic cancer in symptomatic patients.

• Treatment Monitoring: Changes in CA 19-9 levels can reflect the effectiveness of treatment.

• Prognosis: Higher levels at diagnosis are often associated with advanced disease and poorer outcomes.

  
  

Non-cancerous conditions like pancreatitis and liver disease can also cause elevated CA 19-9 levels, requiring careful interpretation.

Human Chorionic Gonadotropin (hCG)

Human chorionic gonadotropin (hCG) is a hormone produced during pregnancy, but it also serves as a tumor marker for certain cancers, including:

• Germ Cell Tumors: Elevated hCG is a hallmark of testicular and ovarian germ cell tumors.

• Gestational Trophoblastic Disease: Conditions like choriocarcinoma are associated with markedly high hCG levels.

  
  

hCG levels are used for diagnosis, monitoring treatment, and detecting recurrence in these cancers.

Cancer Antigen 15-3 (CA 15-3) and Cancer Antigen 27.29 (CA 27.29)

CA 15-3 and CA 27.29 are associated with breast cancer and are often used for:

• Monitoring Treatment: These markers help evaluate response to therapy in patients with advanced breast cancer.

• Detecting Recurrence: Rising levels can indicate disease recurrence.

  
  

Neither marker is recommended for early detection due to low sensitivity and specificity.

Thyroglobulin (Tg)

Thyroglobulin (Tg) is a protein produced by the thyroid gland and is an important tumor marker for:

• Differentiated Thyroid Cancer: Tg levels are used to monitor patients after thyroidectomy or radioactive iodine therapy. Undetectable or low levels typically indicate successful treatment, while rising levels suggest recurrence.

  
  

Anti-thyroglobulin antibodies can interfere with Tg measurement, so testing for these antibodies is also necessary.

Beta-2 Microglobulin (B2M)

Beta-2 microglobulin (B2M) is a tumor marker for blood cancers such as multiple myeloma and certain lymphomas. Its roles include:

• Prognosis: Elevated B2M levels are associated with advanced disease and poorer prognosis.

• Treatment Monitoring: Changes in B2M levels reflect treatment response.

  
  

B2M can also be elevated in non-malignant conditions such as chronic kidney disease.

Lactate Dehydrogenase (LDH)

While not specific to cancer, lactate dehydrogenase (LDH) serves as a general marker of cell turnover and is elevated in many malignancies, including lymphomas, leukemias, and germ cell tumors. It is often used to:

• Assess Disease Activity: High LDH levels may indicate aggressive or advanced disease.

• Monitor Treatment: LDH levels can decrease in response to successful therapy.

  
  

Elevated LDH levels can also result from non-cancerous conditions such as hemolysis and tissue injury.

Novel and Emerging Serum Tumor Markers

Advances in molecular diagnostics and proteomics have led to the development of novel serum tumor markers, including:

• Circulating Tumor DNA (ctDNA): Fragments of tumor DNA circulating in the blood, offering insights into tumor genetics and actionable mutations.

• Proteomic Markers: Panels of proteins associated with specific cancer types.

• MicroRNAs: Small, non-coding RNAs being studied as potential biomarkers for early cancer detection.

  
  

While many of these are still in the research or early clinical stages, they hold promise for improving the accuracy and utility of tumor marker testing.

Challenges and Limitations of Serum Tumor Marker Testing

Despite their utility, serum tumor markers have limitations. They often lack specificity, as many markers can be elevated in non-cancerous conditions. Additionally, not all cancers produce detectable levels of markers, and levels can vary among patients with the same type of cancer. As such, tumor markers are most effective when used in conjunction with other diagnostic tools, such as imaging and biopsy.