Tumor Markers in Cancer Detection

Tumor Markers

• Tumor markers are used clinically to detect, stage, and monitor cancer.
• Specificity and sensitivity are crucial for clinical utility.
  • Sensitivity: The ability to detect all patients with a specific cancer.
  • Specificity: The ability to distinguish a specific cancer from benign conditions or other cancers.

Common Tumor Markers

• p53:
  • Abnormal p53 may be indicated by anti-p53 antibodies.
  • Abnormal p53 is associated with Ki-67 (marker for proliferation) and ER expression in breast cancer.
• BRCA1:
  • Found in 50% of inherited breast cancer cases.
  • Also found in ovarian, colon, and prostate cancers.
• BRCA2:
  • Found in 70% of inherited breast cancer cases not caused by BRCA1 mutations.
  • Associated with male breast cancer.
• Cell Adhesion Molecules:
  • Used in tumor metastasis.
  • Types include integrins, selectins, cadherins.
  • Elevated levels of ICAM, VCAM, and E-selectin in late-stage breast cancer and gastric cancer.
  • Elevated VCAM is associated with shorter survival.
• Prostate-Specific Antigen (PSA):
  • PSA density: PSA divided by the volume of the prostate gland (measured via transrectal ultrasound).
  • PSA density can be used in conjunction with digital rectal exams.
• Alpha-Fetoprotein (AFP):
  • Found in fetal hepatocytes.
  • Elevated levels are found in hepatocellular carcinoma (HCC) and yolk-sac derived germ cell tumors.
  • AFP levels can be transiently elevated during pregnancy and in benign liver disease.
  • Combination with ultrasound testing increases sensitivity in detecting HCC.
  • Can be used for prenatal screening of neural tube defects.
• Human Chorionic Gonadotropin (hCG):
  • Analysis of serum hCG subunits is particularly useful for managing patients with germ cell tumors.
  • Elevated levels are specific for small cell lung cancer (SCLC).
  • Also found in neuroblastoma, carcinoid, and pheochromocytoma.
• Neuron-Specific Enolase (NSE):
  • Primarily associated with gastrointestinal cancers, particularly colorectal cancer.
  • It is commonly elevated in other cancers, making it generally non-specific.
  • Used to follow patients during therapy and to detect recurrence after surgery.
  • Levels can be increased by liver damage, radiation, or chemotherapy.
• CA 15-3:
  • Primarily associated with breast cancer.
• CA 125:
  • Primarily associated with ovarian cancer.
• CA 19-9:
  • Primarily associated with pancreatic cancer.

Tumor Marker Limitations

• Tumor markers are not diagnostic tools.
• They are adjunct tests used in conjunction with clinical findings and medical imaging.
• Tumor markers may be present in non-malignant conditions, leading to lower specificity.
• Tumor markers may not be present in associated cancers, leading to lower sensitivity.

Tumor Marker Applications

• Staging and Prognosis:
  • Pre-therapeutic levels of tumor markers are used as prognostic factors due to their correlation with metabolic activity, tumor size, and invasion.
  • High levels can suggest more rigorous or systemic treatment.
• Monitoring:
• Tumor marker blood levels can monitor treatment effectiveness.
• Elevated levels after treatment may indicate incomplete tumor removal, recurrence, or metastasis.
• Detection of Recurrence:
  • Tumor markers can detect cancer recurrence 3 to 6 months before clinical or radiological evidence appears.
  • Specificity is not a major issue for this application.

Recommendations for Ordering Tumor Markers

• Never rely on the results of a single test.
• Tumor markers are non-specific.
• Use multiple markers to improve diagnostic yield.

Hook Effect

• Known as the Prozone Effect.
• Occurs when antigen concentration is very high, resulting in false-negative results.
• A hook effect is probable when AFP levels are considerably higher than 0.1 ng/mL.