Oncogenic Markers Notes

INTRODUCTION

  • Tumor markers are biochemical substances like hormones, enzymes, or proteins.
  • Production:
    • Directly by cancer cells or
    • Synthesized by the body in response to a tumor.
  • Key Uses:
    • Detect, monitor, and support cancer diagnosis.
  • Detection Locations:
    • Blood circulation
    • Body fluids (e.g., urine, cerebrospinal fluid)
    • Tissue samples

METHODS FOR DETECTION

  1. Immunohistological and immunocytological tests:

    • Detect tumor markers on cell membranes and cytoplasm.
    • Examples:
      • Immunofluorescence
      • Immunoperoxidase
      • Monoclonal antibody technology

  2. Biochemical methods:

    • Measure tumor markers in blood circulation.
    • Examples:
      • Radio-immuno assay (RIA)
      • Enzyme immune assay
      • Immunochemical reactions

LABORATORY METHODS USED

  • Method | Platform | Markers Measured
  • Chemiluminescence Immunoassay (CLIA) | DXI 800, Access 2 | PSA, hCG, CA-125, CEA, AFP
  • ELISA | Manual/automated systems | Ferritin, CEA
  • Electrochemiluminescence (ECL) | Cobas e601 | PSA, hCG, CA markers, AFP
  • Nephelometry | IMMAGE 800 (limited) | Some protein-based tumor markers

CHARACTERISTICS OF AN IDEAL TUMOUR MARKER

  1. Analytical Criteria

    • High sensitivity and able to detect very low concentrations.
    • High specificity (measures only particular tumor marker).
    • High accuracy and precision.

  2. Clinical Criteria

    • Disease-sensitive and positive in all patients with particular cancer.
    • No false negatives.
    • Should correlate with cancer extent and volume and should be stable.
    • Specific to one cancer type, not detectable in healthy individuals nor in benign tumors.
    • Correlates with prognosis and ability to detect relapses/recurrences.

CLINICAL USES OF TUMOR MARKERS

  1. Screening and early diagnosis (especially for asymptomatic individuals).
  2. Cancer diagnosis.
  3. Prognostic predictor.
  4. Clinical staging adjunct.
  5. Monitoring treatment progress.
  6. Early relapse/recurrence detection.

TYPES OF TUMOUR-MARKERS

  1. Tumor-specific antigens:

    • Direct products of oncogenesis (triggered by oncogenes, radiation, carcinogens).
    • Unique neo-antigens specific to malignant cells.

  2. Tumor-associated antigens:

    • Found in embryofetal tissues and cancer cells.
    • Re-express in malignancies during adulthood (retrogenetic expression).
    • Examples: CEA, AFP.

CLASSIFICATION OF TUMOUR MARKERS

  • Tumor Associated Antigens:
    1. Carcinoembryonic antigen (CEA)
    2. α-Fetoprotein (AFP)
    3. Tissue polypeptide antigen (TPA)
    4. Pancreatic oncofetal antigen (POA)
  • Pregnancy Associated Antigens:
    1. Human chorionic gonadotropin-β subunits (β-HCG)
    2. Placental-like alkaline phosphatase (Regan isoenzyme-PLAP)
    3. Pregnancy specific glycoprotein (SP-1)
    4. Human placental lactogen (HPL)
  • Hormones Used as Tumor Markers:
    1. Parathormone (PTH)
    2. Calcitonin
    3. Growth hormone (GH)
    4. ACTH
    5. Insulin
    6. Glucagon
    7. Catecholamines
    8. Serotonin

CLINICAL SIGNIFICANCE OF PSA (Prostate-Specific Antigen)

  • Role: Regulates seminal fluid viscosity and aids sperm motility.
  • Forms in Circulation:
    • Free PSA
    • Complexed PSA (70–90% of circulating PSA).
  • Clinical Applications:
    1. Screening for prostate cancer.
    2. Monitoring cancer progression and recurrence.
    3. Cohesively used alongside Digital Rectal Exam (DRE).
  • Causes of Elevated PSA:
    • Prostate infections, irritation, BPH, recent ejaculation, DRE.

CLINICAL SIGNIFICANCE OF AFP (Alpha-Fetoprotein)

  • Function: Synthesized during fetal life, peaking around 30 weeks.
  • Elevated in:
    1. Hepatocellular carcinoma (HCC)
    2. Certain germ cell tumors.
  • Clinical Uses of AFP:
    1. Assist in HCC diagnosis in at-risk patients.
    2. Stage the disease.
    3. Monitor treatment response.
    4. Detect post-surgery or therapy recurrence.

HCG (Human Chorionic Gonadotropin)

  • Function: Promotes implantation of the blastocyst and maintains the corpus luteum.
  • Clinical Uses:
    1. Confirming pregnancy.
    2. Tumor marker for certain malignancies including gestational trophoblastic tumors and nonseminomatous germ cell tumors.

CARCINOEMBRYONIC ANTIGEN (CEA)

  • Properties: Oncofetal antigen expressed in fetal development, re-expressed in malignancy.
  • Clinical Relevance:
    1. Prognostic indicator for colorectal and other cancers.
    2. Monitoring tumor burden and treatment responses.