tumor markers

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Clinical Chemistry
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1

cancer

autonomous growth of tissue

2

neoplasm

solid mass or tumor

3

oncogenes

promote proliferation of normal cells

4

tumor-suppressor genes

counter-balance of oncogenes

5

tumor growth

activation or alternation of oncogene expression or loss of inactivation of tumor-suppressor gene

6

metastasis

spread outside primary site

7

tumorigenesis

growth and development of a normal cell loses control and tumor cells emerge

8

hyperplasia

multiplication of cells in an organ or tissue

9

neoplasia

cancerous cell proliferation

10

benign

tumor at primary site; less risk; resection possible

11

malignant

cancerous cells

12

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

13

stage I

localized primary tumor

14

stage II

invasion of primary tumor through epithelium and into blood vessels

15

stage III

migration of tumor into regional lymph nodes

16

stage IV

metastasis and invasion of tumor and distant tissues

17

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

18

enzymes

levels of certain chemicals correlate with tumor burden, the extent of tumor growth

19

enzymes

ALP, neuron-specific enolase

20

serum proteins

B-2 microglobulin and immunoglobulins

21

serum proteins

free light chains, M protein, B2 microglobulin

22

endocrine tumor markers

specific markers for secreting tumors

23

endocrine tumor markers

ACTH, ADH, c-peptide, calcitonin, chromogranin A, cortisol, gastrin, GH, HVA, 5-HIAA, metanephrines, PTH, PRL, VMA

24

oncofetal antigens

carcinoembryonic, alpha-fetoprotein

25

oncofetal antigens

nonseminomatous, seminioma, CA 19-9, CA 15-3, CA 27-29, CA 125

26

receptors

nonserologic; estrogen and progesterone receptors

27

receptors

estrogen, progesterone, Her-2/neu, epidermal growth factor

28

screening

indicator for biopsy; PSA

29

diagnosis

high levels indicative of disease; metanephrines, HVA/VMA, PTH, prolactin, chromogranin A, cortisol, ACTH

30

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

31

monitor treatment

monitor efficacy of chemotherapy; residual disease after surgery; CA-125, CA 19-9, CEA, AFP, hCG, PSA, SPE

32

detection of recurrence

increased associated with relapse; CA 15-3, CA-125, CEA, AFP, hCG, PSA

33

tumor specific, absent in healthy individuals and readily detectable in body fluids

three factors of the ideal tumor marker

34

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

35

BRCA1 and 2 mutations

germ line used to identify susceptibility to breast and ovarian cancers

36

adenomatous polyposis coli gene (APC)

germ line used to identify susceptibility to colon cancer

37

lack of standardization

biggest challenge in tumor marker measurement

38

immunoassay

most commonly used method to measure tumor markers; advantage-automate testing; linearity, hook effect, and heterophile antibodies

39

linearity

determined by analyzing (in replicates) specimens spanning the reportable range

40

linear range

span of analyte concentrations over which a linear relationship exists between the analyte and the signal

41

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

42

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

43

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

44

neuroblastoma

diagnosed by the detection of high levels of plasma epinephrine, norepinephrine, and dopamine

45

pheochromocytoma

a rare tumor associated with hypertension, diagnosed by detecting elevated plasma metanephrines

46

carcinoid tumors

serotonin-secreting tumors that arise from small intestine, appendix, or rectum

47

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

48

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

49

ALP

elevated in bone, liver, leukemia, and sarcoma cancers

50

creatine kinase-BB

elevated in prostate, small cell lung, breast, colon, and ovarian cancers

51

lactate dehydrogenase

elevated in liver, lymphomas, leukemia cancers

52

PSA

elevated in prostate cancer

53

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

54

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

55

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

56

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

57

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