Clinical Chemistry: tumor markers Flashcards
cancer
autonomous growth of tissue
neoplasm
solid mass or tumor
oncogenes
promote proliferation of normal cells
tumor-suppressor genes
counter-balance of oncogenes
tumor growth
activation or alternation of oncogene expression or loss of inactivation of tumor-suppressor gene
metastasis
spread outside primary site
tumorigenesis
growth and development of a normal cell loses control and tumor cells emerge
hyperplasia
multiplication of cells in an organ or tissue
neoplasia
cancerous cell proliferation
benign
tumor at primary site; less risk; resection possible
malignant
cancerous cells
metastasis
multiple genetic changes; growth regulation imbalance, uncontrolled proliferation; numerous tumor cell-host cell and cell-matrix interactions; cells penetrate primary site boundaries, invade blood or lymphatics, arrest in secondary site to begin growth
stage I
localized primary tumor
stage II
invasion of primary tumor through epithelium and into blood vessels
stage III
migration of tumor into regional lymph nodes
stage IV
metastasis and invasion of tumor and distant tissues
tumor marker
produced directly by the tumor or an effect that the tumor has on healthy tissue; substance found in increased amount in blood, body fluids, or tissues that may suggest a type of cancer
enzymes
levels of certain chemicals correlate with tumor burden, the extent of tumor growth
enzymes
ALP, neuron-specific enolase
serum proteins
B-2 microglobulin and immunoglobulins
serum proteins
free light chains, M protein, B2 microglobulin
endocrine tumor markers
specific markers for secreting tumors
endocrine tumor markers
ACTH, ADH, c-peptide, calcitonin, chromogranin A, cortisol, gastrin, GH, HVA, 5-HIAA, metanephrines, PTH, PRL, VMA
oncofetal antigens
carcinoembryonic, alpha-fetoprotein
oncofetal antigens
nonseminomatous, seminioma, CA 19-9, CA 15-3, CA 27-29, CA 125
receptors
nonserologic; estrogen and progesterone receptors
receptors
estrogen, progesterone, Her-2/neu, epidermal growth factor
screening
indicator for biopsy; PSA
diagnosis
high levels indicative of disease; metanephrines, HVA/VMA, PTH, prolactin, chromogranin A, cortisol, ACTH
prognosis
associated with high levels of tumor marker; receptor status used for indication of chemotherapy; B2-microglobulin, CA-125, CEA, LD, Her-2/neu, ER, PR
monitor treatment
monitor efficacy of chemotherapy; residual disease after surgery; CA-125, CA 19-9, CEA, AFP, hCG, PSA, SPE
detection of recurrence
increased associated with relapse; CA 15-3, CA-125, CEA, AFP, hCG, PSA
tumor specific, absent in healthy individuals and readily detectable in body fluids
three factors of the ideal tumor marker
susceptibility
can be determined using molecular diagnostics in patients with breast, ovarian, or colon cancers by identifying germ-line mutations in patients with a family history of these diseases
BRCA1 and 2 mutations
germ line used to identify susceptibility to breast and ovarian cancers
adenomatous polyposis coli gene (APC)
germ line used to identify susceptibility to colon cancer
lack of standardization
biggest challenge in tumor marker measurement
immunoassay
most commonly used method to measure tumor markers; advantage-automate testing; linearity, hook effect, and heterophile antibodies
linearity
determined by analyzing (in replicates) specimens spanning the reportable range
linear range
span of analyte concentrations over which a linear relationship exists between the analyte and the signal
hook effect
when analyte concentrations exceed the analytical range excessively, potential for antigen excess; capture and label ABs are saturated, resulting in lack of sandwich formation resulting in decrease in signal; refers to shape of concentration signal curve; dilute and retest
heterophile antibodies
circulating antibodies against animal immunoglobulins can cause significant interference in immunoassays; occur in patients given mouse monoclonal antibodies for therapeutic reasons or who have been exposed to mice
high performance liquid chromatography
commonly used to detect small molecules; most widely used method to detect catecholamines and their metabolites in plasma and urine; analytes are separated, run over a column, separated again by physical characteristics; used for neuroblastoma, pheochromocytoma, and carcinoid tumors
neuroblastoma
diagnosed by the detection of high levels of plasma epinephrine, norepinephrine, and dopamine
pheochromocytoma
a rare tumor associated with hypertension, diagnosed by detecting elevated plasma metanephrines
carcinoid tumors
serotonin-secreting tumors that arise from small intestine, appendix, or rectum
immunohistochemistry and immunofluorescence
test tumor markers that are detected directly within solid tissue; identified in tissue sections typically from fine-needle aspirate or biopsy samples; slice of tissue placed on glass slide and incubated with specific antibodies in solution to detect presence of antigens; estrogen and progesterone receptors in breast cancer is an example
enzyme assays
detection of elevated circulating chemicals generally cannot be used to identify a specific tumor or site of tumor, except PSA; was widely used before immunoassays and oncofetal antigens; examples: ALP, CK-BB, LDH, PSA
ALP
elevated in bone, liver, leukemia, and sarcoma cancers
creatine kinase-BB
elevated in prostate, small cell lung, breast, colon, and ovarian cancers
lactate dehydrogenase
elevated in liver, lymphomas, leukemia cancers
PSA
elevated in prostate cancer
alpha-fetoprotein (AFP)
serum protein synthesized by fetal liver and reexpressed in certain types of tumors; often elevated in hepatocellular carcinomas and germ cell tumors; a 70-kD glycoprotein related to albumin; normally functions as transport protein involved in regulating oncotic pressure in fetus; upper limit of normal for serum 15ng/mL in adults; used to monitor, classify, and stage testicular cancer and therapy; sandwich immunoassay using monoclonal or polyclonal AB
cancer antigen 125 (CA-125)
useful in detecting ovarian tumors at early stage and monitoring treatment without surgical restaging; expressed in ovary, other tissues of mullerian duct origin and ovarian carcinoma cells; only marker for ovarian cancer; immunoassays using OC125 and M11 antibodies
carcinoembryonic antigen (CEA)
discovered in '60s as prototype example of oncofetal antigen; expressed during development and reexpressed in tumors; most widely used for colorectal cancer; also elevated in lung, breast, and GI tumors; large heterogenous glycoprotein; 200kDa; part of Ig family involved in apoptosis, immunity, and cell adhesion; used for prognosis, postsurgery surveillance, and monitor chemo treatment; historically-polyclonal AB, now monoclonal anti-CEA Ab; not recommended for screening; high heterogeneity-serial monitoring has to be same assay
human chorionic gonadotropin (hCG)
dimeric hormone secreted by trophoblasts in placenta to maintain corpus luteum during pregnancy; 45-kD glycoprotein consisting of alpha and beta subunits; prognosis of ovarian cancer, diagnosis of testicular cancer, most useful marker for gestational trophoblastic disease; immunoassay w/ monoclonal capture, tracer Abs
prostate specific antigen
28-kD glycoprotein produced only in epithelial cells of acini and in prostatic ducts; regulates seminal fluid viscosity; dissolves cervical mucous cap, allowing sperm to enter; low levels detected in healthy men; two major forms: free and complexed; increased in infection, irritation, or enlargement of gland; monitors progression after radiation or endocrine therapy; 50+ screened annually; normal <4ng/mL; automated immunoassay using enzyme, fluorescence, or chemiluminescence