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53 Cards in this Set
- Front
- Back
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Tumor Marker
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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.
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Normal cell
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expression of a receptor (marker) which influences the rate of cell growth or differentiation
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Cancer cell
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overexpression of receptors
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Diagnostic sensitivity
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- % 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) |
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Diagnostic specificity
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- % 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 |
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ROC Curve
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- receiver operating characteristic curve
- selection of cutoff levels to define disease - y-axis: true positive rate (sensitivity) - x-axis: false positive rate (1-specificity) |
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Analytic sensitivity
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ability of an analytical method to detect small quantities of the measured component, the lower detection limit of a test
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Analytic specificity
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ability of an analytical method to detect only the component(s) it is designed to measure, a lack of cross-reactivity with other substances
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Clinical Utility of Tumor markers
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1.) Screening
2.) Monitor treatment 3.) Detect disease recurrence |
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Screening
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- Lack sensitivity and specificity for screening the general population
- Defined populations |
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Monitor treatment
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- Determine therapeutic effectiveness
- [marker] approaches normal if patient responding to treatment |
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Detect disease recurrence
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- Level increases with tumor progression
- Highest if metastases present |
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Testing considerations
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- Serial testing
- Half-life of marker - Use of same method & laboratory |
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Alpha-fetoprotein, “AFPTM"
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- alpha-fetoprotein
- hepatic cancer |
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Carcinoembryonic antigen (CEA)
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- a glycoprotein
- GI cancers (colorectal) |
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AFP and CEA
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- 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 |
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Carbohydrate Antigens AKA Cancer Antigens
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1.) CA 125
2.) CA 19-9 |
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CA 125
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- ovarian carcinoma
- monitor treatment - detection of recurrence - Screening (low sensitivity) |
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CA 19-9
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- 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 |
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Markers associated with breast cancer
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1.) CA 27-29
2.) CA 15-3 |
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CA 27-29
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- Detect metastasis, esp. bone
- Monitor patients with advanced disease |
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CA 15-3
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- 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 |
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Tissue markers: breast cancer
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1.) Estrogen receptor (ER) & Progesterone receptor (PgR)
2.) HER-2/neu |
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Estrogen receptor (ER) & Progesterone receptor (PgR)
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- 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 |
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HER-2/neu
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- (c-erb B2) oncoprotein
- c-erb B2 gene amplified - correlates with poor prognosis - presence of this protein dictates treatment with Herceptin |
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Prostate Specific Antigen
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1.) total PSA (tPSA)
2.) free PSA 3.) fPSA/tPSA |
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total PSA (tPSA)
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- 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 |
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free PSA
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- glycoprotein with protease activity
- produced by specialized epithelial cells of the prostate |
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fPSA/tPSA
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- expressed as %PSA helpful in differentiating between benign prostatic hyperplasia (BPH) and prostate tumors
- an increase in % means benign and better |
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beta-2-microglobulin (b2M)
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- 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 |
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Human Chorionic Gonadotropin (HCG)
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- 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 |
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Phaechromocytomas
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- Benign or malignant tumors
- Arise from neurochromaffin cells of the autonomic nervous system or adrenal medulla (90%) - increase production of catecholeamines |
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Neuroblastoma
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- One of most common malignancies in children
- > 90% associated with an increased production of catecholeamines - Dopamine excretion most characteristic (also HVA and VMA) |
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Chromogranin A
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- 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 |
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Catecholamine metabolites
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1.) Homovanillic acid (HVA)
2.) Vanillylmandelic acid (VMA) 3.) Metanephrines - specimen: 24 hour urine |
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Homovanillic acid (HVA)
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Neuroblastoma screen
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Vanillylmandelic acid (VMA)
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- Principal end product of epinephrine and norepinephrine metabolism
- Phaeochromocytoma, neuroblastoma screening |
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Metanephrines
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- Inactive metabolites of epinephrine
- Single most sensitive phaeochromocytoma screen |
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Catecholamine metabolites laboratory method
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1.) Sandwich immunoassays & ELISA (Enzyme linked immunosorbent assay)
2.) Nephelometry/Turbidmetry |
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Assay problems
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- HAMAS: human anti-mouse antibodies interferes with Ab-Ag-Ab sandwich formation
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Nephelometry/Turbidmetry
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- detects rate of Ab-Analyte complex formation under conditions of Ab excess
- hook effect: Analyte (antigen) concentration is extremely high: false low reading |
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Proteomics
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- 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 |
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Genomics
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- Detection of gene mutations
- Oncogenes - Tumor suppressor genes - Genes regulating DNA repair, apoptosis, cell cycle |
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Cancer accounts for what percentage of deaths in the United States annually?
A.) 5% B.) 13% C.) 20% D.) 23% |
D.) 23%
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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
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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
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Which of the following is an oncofetal antigen?
A.) alpha-Fetoprotein B.) LD C.) PAP D.) Neuron-specific enolase |
A.) alpha-Fetoprotein
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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
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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
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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
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Which of the following enzymes is commonly used as a tumor marker?
A.) Lipase B.) LD C.) Aldolase D.) Catalase |
B.) LD
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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
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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
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