Tumor Markers Flashcards
Define Tumor Marker
Biomarker found in the blood or tissue and when elevated is linked to cancer
How are tumor markers produced?
Directly by the tumor or as an effect of the tumor on healthy tissue
Tumor markers can take the form of what molecule(s)?
Hormones, metabolites, receptors, enzymes, oncofetal antigens
Enzyme tumor markers
Clinically useful for monitoring the success of therapy and correlate to tumor burden
Elevated non specifically
Serum Protein tumor markers
Used to monitor cancer therapy
Beta-Macroglobulin
Is a serum protein tumor marker that is found on the surface of all nucleated cells
A non specific marker of high cell turnover that is common in tumors
Immunoglobulins
A serum protein tumor marker that provides a relatively specific measure of plasma cell production of monoclonal proteins in multiple myeloma
Endocrine Tumor Markers
Used in endocrine malignancies. It is valuable in diagnosing neuroblastomas, pituitary and adrenal adenomas
Oncofetal antigens
Expressed transiently during normal development
Turned on again in formation of tumors
CEA and AFP
Carbohydrate and cancer antigen tumor markers
Monoclonal defined antigens identified from human tumor extracts and cell lines
Best used for monitoring treatment of tumors that secrete these epitopes
Carbohydrate and cancer antigen tumor markers are antibodies that are directed towards what?
Specific carb or cancer antigens.
Best for monitoring treatment of tumors that secrete CA19-9, CA 15-3, CA27-29, and CA-125
Receptor tumor markers are non serological markers that help choose between __a__ and __b__ therapies
A) Endocrine
B) Cytotoxic
What characteristics make an ideal tumor marker?
- Tumor specificity
- Absent in healthy individuals
- Readily detectable in body fluids
T/F:
Tumor markers are found in only cancer
FALSE:
Most are found in normal and benign cells as well as cancer
T/F:
Tumor marker concentration increases with tumor progression
TRUE
Highest level of tumor marker is with ___
Metastasis
What are the two major considerations for tumor marker measurement?
1) Lack of standardization makes comparison of serial results difficult
2) The wide range of tumor marker concentrations encountered clinically
Immunoassays
Common method that allows automation and is relatively easy to use.
What are three unique factors of immunoassays
- Assay linearity
- Antigen excess (hook effect)
- Potential for heterophile antibodies
What is the Hook Effect
When analyte concentrations exceed the analytical range excessively and there is potential for antigen excess.
What should you do if you get a linear result in the immunoassay?
Dilute the specimen and analyze it again. Do not give linear results
What are common analyte concerns with tumor maker immunoassays?
- Icterus
- Lipemia
- Hemolysis
- Antibody cross-reactivity
- Carry Over
What is commonly used to detect endocrine metabolites (small molecules)
High performance Liquid Chromatography (HPLC)
Extractions in HPLC are applied to column and separated by what?
Charge, size, and polarity
T/F:
HPLC is useful to detect hormones and metabolites secreted by tumors. It is helpful in diagnosis, therapeutic monitoring, and recurrence.
TRUE
What are the advantages to HPLC?
- Not subject to Hook Effect
- No lot-to-lot variation
- No interference from heterophile antibodies
What are disadvantages to HPLC?
- Labor intensive
- More experience and skill required than automated
Immunohistochemistry and Immunofluorescence require what type of specimen?
Fine needle aspiration or biopsy. This is for solid tissue tumor markers. Uses colorimetric or fluorescent secondary antibodies to detect the presence or absence of antigens
T/F:
Enzyme assays can be used to specifically identify a type of tumor
FALSE
What are examples of enzyme assays?
ALP: bone, liver, leukemia, sarcoma
LDH: liver, lymphomas, leukemia
PSA: Prostate
Which tumor marker is involved in regulating fetal onconic pressure?
AFP
In what patients is AFP elevated?
Hepatocellular carcinoma (HCC) and germ cell tumors
Seminomatous cancer
formed directly from malignant germ cells
Nonseminomatous cancer
differentiate into embryonal carcinoma, teratoma, choriocarcinoma, yolk sac tumors
What other conditions can AFP be elevated in?
Pregnancy, non-malignant liver disease, testicular cancer
AFP is used with HCG to classify ____ tumors
nonseminomatous
Which of the following is NOT a clinical application of AFP:
1) Primary testing for seminomatous cancer
2) monitor therapy
3) detect residual tumor
4) Monitor relapse
5) maternal screening
5) Neural tube defects and chromosomal abnormalities
1) seminomatous cancer.
AFP can help classify nonseminomatous cancer.
When would CA 125 be elevated?
In patients with endometriosis, 1st trimester of pregnancy, or during menstruation
CA125 is a serological marker for what?
Ovarian cancer
T/F:
CA125 can distinguish between benign masses and ovarian cancer
TRUE
CEA is expressed when?
During development and re-expressed in tumors
CEA is used to aid the diagnosis, prognosis, and therapy monitoring of ___
Colorectal Cancer
T/F:
CEA is only involved in immunity and cell adhesion
FALSE
CEA is involved in apoptosis, immunity, and cell adhesion
T/F:
CEA is measured to confirm the successful removal of tumor burden
TRUE
hCG is a dimeric hormone that is secreted by ___
trophoblasts
hCG is elevated in what?
Trophoblastic tumors, mainly choriocarnicona and germ cell tumors of ovaries and testes
Gestational trophoblastic diseases (GTDs) consist of what 4 distinct types of tumors?
Hydatiform mole
Persistent/invasive gestational trophoblastic neoplasia
Choriocarcinoma
Placental Site Trophoblastic tumors
Why is total beta-hCG is the most helpful?
Because it detects both intact and free beta-hCG
What is structure of PSA?
Glycoprotein that is produced in the epithelial cell of the acini and ducts of the prostate gland
What is the function of PSA
Regulates seminal fluid viscosity. It is instrumental in dissolving the cervical mucus cap allowing sperm to enter
The most circulating form of PSA is ___
Bound
T/F:
Malignancy will have a higher % of free PSA
FALSE
Malignancy will have a lower % of free PSA
Increases in PSA can be caused by what?
- Prostate infection
- Irritation
- Enlargement
- Recent ejaculation
- DRE
What are known interferences for PSA?
Hook effect and HAMAs
CA 15-3 is normally expressed where?
Glandular or luminal epithelial cells
What is Mucin 1 (MIC1)?
A transmembrane glycoprotein that is the most researched tumor associated antigen
CA15-3 is useful in manging what type of cancer?
Breast cancer
CA19-9 is useful in diagnosing and monitoring what type of cancer?
Serial pancreatic cancer
When is CA19-9 elevated?
In GI malignancies and benign conditions such as pancreatitis and cholestasis
Ig Free light chains are useful in monitoring what type of patients?
Patients without a M spike on SPE
What chains are measured in FLC?
Kappa and Lambda ratio
What conditions produce increased immunoglobulins?
Multiple Myeloma and Waldenstrom Macroglobulinemia
How is serum kappa and lambda measured?
Nephelometry
The following are the major clinical applications of what?
- Minimizes need to quantitate or perform urine pelp
- Provides DX value in plasma cell dyscrasias
- Allows monitoring of patients who previously deemed to have non secretory myeloma
FLC
HE4 is shown to be overexpressed in what type of cancer?
Ovarian cancer
Why do you need to reject hemolyzed samples when testing NSE levels?
Because NSE levels are present in RBCs
What does NSE aid in in terms of DX?
Helps differential DX of neurodegenerative disorders
NSE is an auxilary test for what?
Small cell lung carcinoma
carcinoid tumors
pancreatic islet cell tumors
neuroblastomas
