What are tumor markers?

Tumor Markers: Definition and Clinical Applications

Tumor markers are substances that can be found in blood, urine, stool, other body fluids, or tissues that may indicate the presence of cancer. These substances are typically produced by cancer cells or by the body in response to cancer or certain benign conditions 1.

Types of Tumor Markers

Tumor markers can be categorized into several types:

1. Serum Tumor Markers

• Alpha-fetoprotein (AFP)

  • Produced by nonseminomatous germ cell tumors (embryonal carcinoma, yolk-sac tumor)
  • Half-life of 5-7 days
  • Elevated AFP in a patient with "pure" seminoma suggests an undetected focus of nonseminoma 1

• Human Chorionic Gonadotropin (hCG)

  • Produced by germ cell tumors
  • Approaches the ideal tumor marker in gestational trophoblastic tumors 2
  • Can be elevated in both seminomas and nonseminomas 1

• Lactate Dehydrogenase (LDH)

  • Less specific marker than AFP and hCG
  • Used in monitoring germ cell tumors 1

• Carcinoembryonic Antigen (CEA)

  • Used primarily in colorectal cancer management
  • Cannot be used for cancer screening
  • Preoperative elevation suggests advanced disease 2

• CA 125

  • Used for monitoring therapy in patients with ovarian cancer 3

2. Tissue Tumor Markers

• Estrogen Receptors (ER)

  • Used for predicting response to hormone therapy in breast cancer 3

• Human Epidermal Growth Factor Receptor 2 (HER2)

  • Identifies women with breast cancer likely to respond to trastuzumab (Herceptin) 3

• KRAS Mutational Status

  • Identifies patients with advanced colorectal cancer likely to benefit from anti-EGFR antibody treatment 3

• Urokinase Plasminogen Activator (uPA) and Plasminogen Activator Inhibitor 1 (PAI-1)

  • Used for determining prognosis in patients with newly diagnosed, node-negative breast cancer 1

Clinical Applications of Tumor Markers

Tumor markers serve several important clinical functions:

1. Diagnosis and Screening

• Most tumor markers lack sufficient sensitivity and specificity for population screening 4
• Some markers can aid in diagnosis when combined with other clinical information
• For example, AFP and hCG are useful in diagnosing germ cell tumors 1

2. Staging and Prognosis

• Elevated marker levels often correlate with more advanced disease
• In testicular cancer, AFP, hCG, and LDH are critical in determining prognosis 1
• In breast cancer, uPA/PAI-1 can help determine prognosis in node-negative patients 1

3. Treatment Monitoring

• Serial measurements can assess response to therapy
• Rising levels may indicate disease progression or recurrence
• For example, CA 125 is used for monitoring therapy in ovarian cancer 3

4. Surveillance After Curative Treatment

• Regular monitoring can detect early relapse
• In testicular cancer, follow-up protocols include regular measurement of AFP, hCG, and LDH 1

5. Predicting Treatment Response

• Some markers can predict response to specific therapies
• HER2 status predicts response to trastuzumab in breast cancer
• KRAS mutation status predicts response to anti-EGFR antibodies in colorectal cancer 3

Limitations of Tumor Markers

• Not all cancer patients have elevated marker levels
• Some non-cancerous conditions can cause elevated marker levels
• Most markers lack sufficient sensitivity and specificity for screening
• Interpretation requires consideration of pre-analytical conditions and patient's concomitant diseases 5

Proper Use of Tumor Markers

• Understand the specific context in which each marker is validated
• Consider patient-specific factors that might affect marker levels
• Use serial measurements rather than single values when monitoring disease
• Interpret results in conjunction with clinical findings and imaging studies
• Follow established guidelines for specific cancer types 1

Example: Tumor Marker Use in Testicular Cancer

The American Society of Clinical Oncology recommends:

• Measuring AFP, hCG, and LDH before and after orchiectomy for testicular nonseminomas
• Measuring these markers before chemotherapy for extragonadal nonseminomas
• Measuring AFP and hCG before retroperitoneal lymph node dissection
• Measuring markers at the start of each chemotherapy cycle
• Periodic monitoring for relapse 1

By understanding the appropriate use and limitations of tumor markers, clinicians can optimize their value in cancer patient management while avoiding potential pitfalls of misinterpretation.