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Tumor Markers

Tumor Markers. Tumor. Tumor refers to the uncontrolled growth of cells that can develop into a solid mass and spread to other areas of the body. The formation (tumorigenesis) and spreading (metastasis) of tumors are caused by a complex combination of inherited and acquired genetic mutations

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Tumor Markers

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  1. Tumor Markers

  2. Tumor • Tumor refers to the uncontrolled growth of cells that can develop into a solid mass and spread to other areas of the body. • The formation (tumorigenesis) and spreading (metastasis) of tumors are caused by a complex combination of inherited and acquired genetic mutations • Tumor can be detected and monitored using biologic tumor markers

  3. Tumor Markers • A Tumor marker is a biological substance synthesized and released by: • the tumor • or by the host in response to tumor tissue. • It may be used to: • Detect the presence of a tumor • Monitor the progress of disease • Monitor the response to treatment

  4. Tumor Antigens • Tumor specific antigens • Direct product of oncogenesis • Disorganization of the genetic information leading to synthesis of antigens that are unique to the specific tumor cell • Tumor associated antigens • Most tumors are not specific for individual tumors but rather are usually associated with different tumors derived from the same or closely related tissue • E.g. Oncofetal antigens: Antigens present in normal fetal growth and stimulated by malignancies later in life

  5. How to identify tumor marker ? • On cell • Immunocytochemistry, Flow cytometry • On tissue • Immunohistochemistry • In body fluids • Blood, urine, CSF, Amniotic fluid • RIA, EIA

  6. Tumor markers in Cancer Management • Screening • Diagnosis • Staging • Prognosis • Monitoring

  7. Tumor markers in Cancer Management

  8. Screening • Tumor markers play a limited role for tumor screening, because • relatively low sensitivity • lack of specificity • Inappropriate for the detection of small in situ cancer • However, successful cancer screening has been carried out by measuring tumor markers • Eg. PSA → prostate cancer

  9. Screening • Susceptibility to cancer can be determined using molecular diagnostics in patients with breast, ovarian, or colon cancer • Screening for susceptibility to breast and ovarian cancers is done by: • identifying germline BRCA1 and BRCA2 mutations. • Similarly, familial colon cancers can be identified by: • the presence of the adenomatous polyposis coli gene (APC)

  10. Diagnosis • Tumor marker is not the key diagnostic examination, but can be a complementary sign to clinical finding or medical imaging • AFP → hepatoma

  11. Staging • The major clinical value of tumor markers is in tumor staging, monitoring therapeutic response and detecting recurrence • The tumor markers and medical imaging are complementary in the pre-therapeutic and post-therapeutic staging

  12. Prognosis • Serum concentration of tumor markers increases with tumor progression and usually reaches the highest levels when tumors become metastasized. • The serum levels of tumor markers at diagnosis are likely to reflect the aggressiveness of the tumor and help predict the outcome for the patients. • High levels indicate the presence of a malignant or metastatic tumor → poor prognosis.

  13. Monitoring and Disease Recurrence • One of the most useful applications of tumor markers is monitoring therapy efficacy and detecting disease recurrence. • After surgical resection, radiation, or drug therapy of cancer (chemotherapy), tumor markers are routinely followed. • In patients with elevated tumor markers at diagnosis, effective therapy results in a dramatic decrease or disappearance of the tumor marker.

  14. Monitoring and Disease Recurrence • If the initial treatment is effective, the appearance of circulating tumor markers can then be used as a highly sensitive marker of recurrence • Many markers have a significant lead time of several months before disease would be detected by other methods, allowing treatment of an earlier-stage cancer.

  15. Ideal Tumor Marker Characteristics • Sensitive & Specific • Presence of a given marker identifies an exact malignancy • Concentration proportional to tumor size • Concentration changes with growth or reduction of malignancy • Concentration is low after remission • Concentration is a good indicator of prognosis • Short half-life (concentration reflects current conditions)

  16. Reality of tumor markers • Unfortunately, most tumor markers only possess some of the ideal characteristics (never all of them) • Most tumor markers are not very sensitive and are poor screening tests for the detection of malignancies • Most tumor markers are best utilized to confirm or monitor already diagnosed cancers

  17. Different Types of Tumor Markers • Fetal antigens • Proteins • Hormones • Enzymes • Steroid Receptors

  18. Oncofetal antigens • Oncofetal antigens expressed transiently during normal fetal development and are then turned on again in the formation tumors

  19. CEA (Carcinoembryonic Antigen ) • Oncofetal antigen • Best tumor marker for monitoring of colon cancer • Also elevated in • Smokers, Alcoholic cirrhosis & Ulcerative colitis • Good correlation with treatment and prognosis of colon cancer • ↓ CEA after surgical removal of tumor • ↑ CEA if malignancy re-occurs or metastasizes • Levels correlate well with chemotherapy and irradiation treatment • Assay: ELISA and RIA

  20. Alpha –FetoProtein (AFP) • Oncofetal antigen • ↑ in pregnancy and certain malignancies • Useful tumor marker for monitoring • Liver cancer, hepatocellular carcinomas (HCC) • Gonadal malignancies • Serial measurements of AFP used to monitor treatment and postsurgery in patients with HCC. • Assay: ELISA and RIA

  21. Prostate Specific Antigen (PSA) • PSA is a tissue specific protein secreted by malignant prostate cells • PSA is present in low concentrations of normal males, but elevated in malignancies and other conditions • Good screening test for the detection of prostate cancer in older males and the monitoring of previously diagnosed tumors • Complete removal of prostate should result in an undetectable total PSA in serum, any measurable tPSA would indicate residual prostatic tissue or metastasis. • Assay: Immunoassays (ELISA)

  22. CA 125 • CA 125 is a protein that is associated with normal ductal tissue • Utilized to evaluate gonadal ovarian cancers • CA125 is not efficient in detecting early (more treatable) ovarian cancers • CA125 is useful in detecting late ovarian cancers and recurrence of cancers • False positives may occur, resulting in unnecessary treatment 75 % of ovarian cancers are not diagnosed until late in the disease. • Assay: ELISA , RIA

  23. Paraproteins • Any of the incomplete monoclonal immunoglobulins that occur in plasma cell disorders • Paraproteins are detectable in either serum or urine in 98-99% of patients with Multiple Myeloma. • Their detection is valuable in the diagnosis of this condition • Paraprotein concentrations correlate well with Tumor bulk • Reduction in the amount of paraprotein is a good indicator of the efficacy of treatment.

  24. Hormones as tumor markers • hCG is a hormone produced by the normal placenta (pregnancy) • The presence of hCG in the plasma at other times indicates the presence of abnormal trophoblastic tissue tumors of the ovary and testis. • It is a prognostic indicator for ovarian cancer, a diagnostic marker for classification of testicular cancer • Assay: ELISA

  25. Enzymes as Tumor Markers • Plasma enzyme activities are often increased in patients with cancer, • usually a secondary effect of the tumor rather than a result of secretion of an enzyme by the tumor. • Examples include the increase in alkaline phosphatase activity seen in patients with bone cancer. • Increase in the plasma activity of the placental type in plasma occurs in many patients with lung, ovarian & others • Measurement of placental alkaline phosphatase is of value in monitoring the response of such patients to treatment.

  26. Steroid Receptors • Hormonally dependent organs (breast) give rise to malignancies that may in themselves be hormonally dependent • Eliminating hormonal stimulation by drugs leads to a regression of the respective malignancy • Predicting which tumor respond to hormonal manipulation can be achieved by measuring steroid hormone receptors on tumors

  27. Estrogen & Progesterone Receptors • It is a protein localized in the nuclei of mammary and uterine tissue. • Patients whose primary tumors demonstrated ER will respond to hormone therapy. • ER and progesterone receptor assays are used to predict the therapeutic response of breast cancer patients to hormonal treatment

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