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53 Cards in this Set

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Tumor Marker
a substance present in, or produced by a tumor itself, or produced by the host in response to a tumor, that is used to differentiate a tumor from normal tissues or to determine the presence of a tumor based on the measurement in the blood or other fluids. It is measured qualitatively or quantitatively by chemical, immunological, genomic, or proteomic methods to identify the presence of a cancer.
Normal cell
expression of a receptor (marker) which influences the rate of cell growth or differentiation
Cancer cell
overexpression of receptors
Diagnostic sensitivity
- % of individuals with a disease that test positively with a test
= # of individuals with the disease who test positive/total # of diseased individuals tested
= TP/(TP+FN)
Diagnostic specificity
- % of individuals without a disease that test negatively with a test
- # of individuals without the disease who test negative/total # of individuals tested without the disease
= TN/(TN + FP) x 100
ROC Curve
- receiver operating characteristic curve
- selection of cutoff levels to define disease
- y-axis: true positive rate (sensitivity)
- x-axis: false positive rate (1-specificity)
Analytic sensitivity
ability of an analytical method to detect small quantities of the measured component, the lower detection limit of a test
Analytic specificity
ability of an analytical method to detect only the component(s) it is designed to measure, a lack of cross-reactivity with other substances
Clinical Utility of Tumor markers
1.) Screening
2.) Monitor treatment
3.) Detect disease recurrence
Screening
- Lack sensitivity and specificity for screening the general population
- Defined populations
Monitor treatment
- Determine therapeutic effectiveness
- [marker] approaches normal if patient responding to treatment
Detect disease recurrence
- Level increases with tumor progression
- Highest if metastases present
Testing considerations
- Serial testing
- Half-life of marker
- Use of same method & laboratory
Alpha-fetoprotein, “AFPTM"
- alpha-fetoprotein
- hepatic cancer
Carcinoembryonic antigen (CEA)
- a glycoprotein
- GI cancers (colorectal)
AFP and CEA
- These two markers are carcinoembryonic proteins
normally produced during fetal development
- AFP Maternal Screen
- suppression of gene expression then leads to lower levels
- associated with carcinogenesis later in life
Carbohydrate Antigens AKA Cancer Antigens
1.) CA 125
2.) CA 19-9
CA 125
- ovarian carcinoma
- monitor treatment
- detection of recurrence
- Screening (low sensitivity)
CA 19-9
- detected as a mucin in serum
- related to Lewis blood group
- only Le(a-b+) or Le (a+,b-) can be CA 19-9 pos
- highest sensitivity: pancreatic & gastric cancers
Markers associated with breast cancer
1.) CA 27-29
2.) CA 15-3
CA 27-29
- Detect metastasis, esp. bone
- Monitor patients with advanced disease
CA 15-3
- expressed by a number of adenocarcinomas
- primarily associated with breast cancer
- > 25 U/mL, seen in ~75% patients with metastases
- also elevated in: liver disease, TB, SLE
- Clinical utility: monitor clinical course of breast cancer patients
Tissue markers: breast cancer
1.) Estrogen receptor (ER) & Progesterone receptor (PgR)
2.) HER-2/neu
Estrogen receptor (ER) & Progesterone receptor (PgR)
- Identification of individuals with breast cancer who will benefit from endocrine therapy
- detected in tumor cytosol
- ER/PgR “rich” tumors: better prognosis than ER/PgR poor
- activity of PgR is ER dependent
- positive for both = best prognosis
HER-2/neu
- (c-erb B2) oncoprotein
- c-erb B2 gene amplified
- correlates with poor prognosis
- presence of this protein dictates treatment with Herceptin
Prostate Specific Antigen
1.) total PSA (tPSA)
2.) free PSA
3.) fPSA/tPSA
total PSA (tPSA)
- free PSA + PSA-ACT complex
- most utilized tumor marker for management of prostate cancer
- cancer screening if in combination with other tests
- following prostatectomy: PSA should be undetectable
- tPSA (often referred to as “PSA”)is relatively low specificity and also elevated in prostatitis, benign prostatic hyperplasia
free PSA
- glycoprotein with protease activity
- produced by specialized epithelial cells of the prostate
fPSA/tPSA
- expressed as %PSA helpful in differentiating between benign prostatic hyperplasia (BPH) and prostate tumors
- an increase in % means benign and better
beta-2-microglobulin (b2M)
- Constant light chain component of HLA antigen
- expressed on most nucleated cells like lymphocytes and monocytes
- low specificity for tumors
- Elevated: solid tumors and lymphoproliferative diseases
inflammatory conditions
Human Chorionic Gonadotropin (HCG)
- sialoglycoprotein secreted by trophoblast cells of normal placenta
- dimer: possesses a- and b-subunit (b-is specific to HCG)
- Hormone of pregnancy
- Elevated in trophoblastic tumors and choriocarcinoma, and germ cell tumors of ovary and testis
- HCGTM = HCG tumor marker
Phaechromocytomas
- Benign or malignant tumors
- Arise from neurochromaffin cells of the autonomic nervous system or adrenal medulla (90%)
- increase production of catecholeamines
Neuroblastoma
- One of most common malignancies in children
- > 90% associated with an increased production of catecholeamines
- Dopamine excretion most characteristic (also HVA and VMA)
Chromogranin A
- soluble protein of catecholamine storage vesicles in adrenal medulla
- present in other neuroendocrine tissues
- primary associations: phaeochromocytoma, neuroblastoma, small cell lung carcinoma, and carcinoid tumor
Catecholamine metabolites
1.) Homovanillic acid (HVA)
2.) Vanillylmandelic acid (VMA)
3.) Metanephrines
- specimen: 24 hour urine
Homovanillic acid (HVA)
Neuroblastoma screen
Vanillylmandelic acid (VMA)
- Principal end product of epinephrine and norepinephrine metabolism
- Phaeochromocytoma, neuroblastoma screening
Metanephrines
- Inactive metabolites of epinephrine
- Single most sensitive phaeochromocytoma screen
Catecholamine metabolites laboratory method
1.) Sandwich immunoassays & ELISA (Enzyme linked immunosorbent assay)
2.) Nephelometry/Turbidmetry
Assay problems
- HAMAS: human anti-mouse antibodies interferes with Ab-Ag-Ab sandwich formation
Nephelometry/Turbidmetry
- detects rate of Ab-Analyte complex formation under conditions of Ab excess
- hook effect: Analyte (antigen) concentration is extremely high: false low reading
Proteomics
- lood for proteins that can be used for diagnosis
1.) Digital in gel electrophoresis (DIGE)
2.) Multidimensional identification technology (MudPIT)
- time consuming
3.) SELDI-TOF
Genomics
- Detection of gene mutations
- Oncogenes
- Tumor suppressor genes
- Genes regulating DNA repair, apoptosis, cell cycle
Cancer accounts for what percentage of deaths in the United States annually?
A.) 5%
B.) 13%
C.) 20%
D.) 23%
D.) 23%
Tumor marker tests are used to:
A.) aid in staging of cancer
B.) monitor response to therapy
C.) detect recurrent disease
D.) all of the above
D.) all of the above
Tumor markers may be defined as:
A.) analytic tests (eg, flow cytometry) used to mark cancer cells
B.) radioactive substances and chemicals used to help the physician identify cancer cells
C.) biologic substances synthesized and released by cancer cells or substances produced by the host in response to cancer cells
D.) none of the above
C.) biologic substances synthesized and released by cancer cells or substances produced by the host in response to cancer cells
Which of the following is an oncofetal antigen?
A.) alpha-Fetoprotein
B.) LD
C.) PAP
D.) Neuron-specific enolase
A.) alpha-Fetoprotein
Which of the following tumor markers is found in both carcinoma and embryonic tissue and is useful as a prognostic indicator in colorectal carcinoma?
A.) AFP
B.) CEA
C.) PAP
D.) CA 120
B.) CEA
The major clinical use for CA 125 is monitoring treatment response of:
A.) ovarian carcinoma
B.) colorectal cancer
C.) prostatic cancer
D.) breast cancer
A.) ovarian carcinoma
Which of the following tumor markers is used in the management of patients with prostatic cancer?
A.) Prostatic acid phosphatase
B.) Prostate-specific antigen
C.) CA 549
D.) Tissue polypeptide antigen
B.) prostate-specific antigen
Which of the following enzymes is commonly used as a tumor marker?
A.) Lipase
B.) LD
C.) Aldolase
D.) Catalase
B.) LD
A tumor marker used in the assessment of choriocarcinoma or hydatidiform mole is:
A.) beta-hCG
B.) CEA
C.) AFP
D.) IgG
A.) beta-hCG
DNA analysis (measuring nuclear DNA content) may be used to:
A.) diagnose cancer
B.) mark cancer cells for removal by surgery
C.) discriminate between benign and malignant disease
D.) detect alterations in genes
D.) detect alterations in genes