Tumor Markers Flashcards
Tumor Marker Makeup
Proteins produced in response to cancer growth or from cancerous tissue
Can be specific or seen in multiple cancer types
Tumor Risk Factors
Genetic mutations
IVDMIA
IVDMIA
(in vitro Diagnostic Multivariate Index Assay)
Tests available to detect mutations and offer “risk index”
Apoptosis
Programmed cell death, self-destruction
Angiogenesis
New blood vessel formation, typically embedded within a tumor, allows tumor cells entry into circulation
Benign
Tumor at the primary site, small risk
Cancer
Abnormal cell growth, proliferation and/or differentiation
Hyperplasia
Multiplication of cells within an organ or tissue, may be controlled by stimuli as a normal response
Malignant
Tumor aggressive progress, infiltration, high risk
Metastasis
Uncontrolled proliferation involving numerous tumor cells and host cells interactions. Penetration into adjacent tissue of primary site, circulatory system, and spread to distant organs.
Neoplasia
Normal cells under cancerous proliferation due to hyperplasia, which is unregulated.
Tumor Marker Utilization
- Screening
- Diagnosis
- Staging
- Determine prognosis
- Guidance of Treatment
- Monitor Treatment
- Determine recurrence
Tumor Marker Utilization: Screening
Useful for patients with a strong family history of a particular cancer. Example: PSA prostate cancer
Tumor Marker Utilization: Diagnosis
In patients with specific clinical symptoms, tumor markers can help identify the source of the cancer and differentiate from other conditions
Examples: CA-125, BRCA1 and BRCA 2
Tumor Marker Utilization: Staging
If a patient does have cancer, tumor marker elevations can be used to help determine how far the cancer has spread into other tissues and organs.
Tumor Marker Utilization: Determine prognosis
Some tumor markers can be used to help doctors determine how aggressive a cancer is likely to be.
Guidance of Treatment
Some tumor markers can provide information about what treatments their patients may have the best response.
Breast cancer patients who are Her2/neu positive are more likely to respond to Herceptin treatment).
Monitor Treatment
Tumor markers can be used to monitor the effectiveness of treatment, especially in advanced cancers. If the marker level drops, the treatment is working; if it stays elevated, adjustments are needed.
Colorectal cancer and CEA testing: information must be used with care; not every colorectal cancer patient will have elevated levels of CEA.
Determine recurrence
To monitor for cancer recurrence - If a tumor marker is elevated before treatment, low after treatment, and then begins to rise over time, then it is likely that the cancer is returning. (If it remains elevated after surgery, then chances are that not all of the cancer was removed)
Tumor Grades
Well differentiated
Poorly differentiated
Anaplastic (without body)
Tumor Marker Classifications
Enzymes
Hormones
Oncofetal Infections
Tumor antigens
Genetic Markers
Enzymes
Catalytic activity vs mass measurements, detected with Immunoassays
Hormones
Immunoassay detection
Oncofetal Infections
AFP, CEA, PSA
Tumor antigens
CA125, CA15-3, CA19-9
Genetic Markers
Oncogene and tumor suppressor mutations
Prostate Specific Antigen, level indications
- Enzyme with protease activity in Prostate tissue
- Exists in serum as bound (complexed with another protease inhibitor) or free, higher free PSA ratio in normal, healthy patients
- Total PSA: 2.6-4ng/mL indicates early development
- 4-10mg/mL is diagnostic gray zone
- >10ng/mL have a 50% chance of having cancer
hCG (Human Chorionic Gonadotropin)
- Synthesized by trophoblast calls in placenta (used for pregnancy detection), made of 2 Alpha and Beta units
- Beta is specific to hCG
- Increased levels assoc. with Trophoblastic tumors, choriocarcinoma, testicular tumors, ovarian tumors
- Immunoassay uses ß-hCG
Oncofetal Proteins
Normally produced in fetal tissues, then decline after birth
A rise later in life (60yrs) can indicate cancer formation
AFP (Alpha feto protein)
- Marks Liver and Germ cell carcinoma, can also appear in viral hepatitis and chronic active hepatitis
- Serum levels correlate to Liver tumor size
- During pregnancy increased levels indiacte spina bifida, neural tube defects, and fetal distress; lowered levels indicate Down’s Syndrome
- Normal adult levels should be lower than 20ng/mL
- Found via enzyme immunoassay
CEA (carcinoembryonic antigen)
- Marker for colorectal, GI, lung, and breast cancer, found normally in GI of fetus
- Not used as a screen as high levels are found in non-cancer patients
- Used for therapy monitoring
- Immunoassayed using mono/poly/both assay
Carbohydrate Tumor Markers
Antigens on tumor cell surface or secreted by the cell
Usually more specific when compared to hormone/enzyme markers
- CA 125: ovarian, endometrial
- CA 15-3, CA 549: breast, ovarian
- CA 19-9: pancreas
- CA 19-5: GI, pancreas
- CA 72-4: Ovarian, breast, GI, colon
- CA 50: Pancreas, GI, colon
Protein Tumor Markers
- Bence-Jones proteins
- C-peptide
- Ferritin
- Immunoglobulins
- Beta2 Microglobulin
C-peptide
Insulinoma
Ferritin
Liver, lung, breast
Immunoglobulins
Multiple myeloma
Beta2 Microglobulin
Multiple myeloma, lymphocytic leukemia
Oncogenes
Normal genes (code for things like growth factor signals) related to tumor virus genes
Their activation is associated with cancer
Test for number of copies of genes, Southern blotting, PCR, FISH, Northern blotting, western blotting, ELISA, and immunohistochemistry)
HER-2/neu
Transmembrane glycoprotein in epidermal growth factor family
Low levels present in breast duct epithelium
Over-expressed in ¼ breast cancers
Levels predict response to Adriamycin-based chemo., and select patients for anti-HER2/neu Ab, predicts poor response to tamoxifin therapy
CA 15-3
- Mucin glycoprotein antigen
- Marker for breast cancer recurrance in previously treated patients
- increased levels may also be found in Hepatitis, tuberculosis, and SLE
CA 125
- Mucin glycoprotein antigen
- Marker for ovarian cancer, used to monitor treatment progress
CA 19-9
- Glycolipid blood group antigen derived from Lewis Blood Group
- Marker for pancreatic, colorectal, lung and gastric carcinomas
- Monitors patients progress