TUMOR MARKERS Flashcards
Tumor Marker types
[6]
enzymes
proteins
hormones
oncofetal antigens
metabolites
receptors
ENZYMES
—Located [inside/outside] the cells; Each organ has specific enzymes
— [Specific/Nonspecific] that can be cancer indicator.
— A variety of enzymes are → # [INC/DEC] nonspecifically in tumors.
- tend to correlate with _______, making them clinically useful for monitoring the success of therapy.
inside
nonspecific
INC
tumor burden
Tumor markers of ENZYMES
[4]
PSA+ACP
LD
ALP
Neuron-specific enolase
an enzyme that is more definitive indicator of cancer
PSA + ACP
Methods for tumor markers:
PSA+ACP
LD
ALP
Neuron-specific enolase
IA
EA
EA
RIA/HCC
Clinical utility for tumor markers:
PSA+ACP
Neuron-specific enolase
Screening: Prostate CA
Therapy: monitoring/recurrence
Prognosticator indicator
Monitoring: progression for neuroendocrine tumors
ENZYMES associated with certain malignant diseases [6]
Lysozyme
LDH
Sialytransferase
Fucosyltransferase
Thymidine kinase
TdT
Malignant disease associated with Lysozyme
Colon cancer
Monocytic/Myelomonocytic Leukemia
Malignant disease associated with LDH
Leukemia
Lymphoma
Breast& Lung cancer
Germ cell tumor
Metastatic colon
Malignant disease associated with Sialytransferase
Nonspecific
Malignant disease associated with Fucosyltransferase
Multiple Malignant tumor
Malignant disease associated with Thymidine Kinase
Hodgkin’s lymphoma
Lung’s small cell carcinoma
Malignant disease associated with Terminal dioxyribonucleotidase transferase
Immature lymphocytes
Isoenzymes associated with malignant diseases
CK-BB
Type 2 Macro-CK
Mitochondrial CK-1IgA complex
Placental like ALP
Liver ALP
Bone ALP
LD1, LD4, LD5
Malignant disease associated with CK-BB
ADENOMA CARCINOMA OF
prostate
stomach
lungs
Malignant disease associated with Type 2 macro-ck
Metastatic liver cancer
Malignant disease associated with Mitochondrial CK-IgA complex
[Prognosticator indicator] advance tumor
Malignant disease associated with Regan
Germ cell tumors
Ovarian cancers
Malignant disease associated with Liver ALP
Liver metastasis
Seminoma
Ovaraian cancer
Malignant disease associated with Bone ALP
Bone metastasis
Osteoma
LD1, LD4, LD5
Advance stage cancer
Testicular germ cell tumor
— Carcinoembryonic proteins produced during fetal dev’t
— [X] indicate cancer BUT as a person grows → these proteins diminishes → & when it is redetected → used as indicator of cancer.
Serum proteins
Under normal conditions expression of all protein is subjected to?
genetic regulation
Tumor markers of serum protein [3]
Serum M-protien
Serum free light chain
B2-microglobulin
Tumor marker of serum protein associated with hematologic malignancies
B2-microglobulin
Methods for tumor markers:
Serum M-protein
Serum free light chain
B2-microglobulin
SPE/IFE
IA
IA
Clinical utility of serum m-protein & serum free light chain
Dx of plasma cell dyscrasia TM
Clinical utility of B2 microglobulin
[Prognostic marker] Lymphoproliferative diseases
— by endocrine organs just like enzymes
— Usually made up of ______.
Widely used as a SPECIFIC MARKERS OF SECRETING TUMORS.
Hormones/Metabolites
When there is an increase in the presence of tumor in the hormone-producing organs what happens? [2]
Tumor compresses the tissues/organs
Overproduction of hormones
Tumor markers of hormones/metabolites [13]
HVA & VMA
Metanephrines
Catecholamines
5’HIAA & Serotonin
Calcitonin
PTH
GH
PRL
ACTH
Cortisol
ADH
Chromogranina
C-peptide
Tumor types/Clinical utility of HVA/VMA
Pheochromocytoma
Paraganglioma
Neuroblastoma
TM types of:
Metanephrines
Catecholamines
Severe aplastic anemia
Pheochromocytoma
Severe aplastic anemia
Pheochromocytoma
Paranganglioma
Neuroblastoma
TM types of 5-HIAA & serotonin
Carcinoid tumors
TM types of Calcitonin
Medullary thyroid cancer
Neuroendocrine tumors
TM types of PTH
Pituitary adenoma
TM types of GH
Pituitary adenoma
Ectopic GH- tumor surgical secreting
Method of PRL
IA
TM types of ACTH
Pituitary adenoma
Ectopic ACTH- producing tumor
TM types of Cortisol
Adrenal tumor
TM types of ADH
Posterior pituitary tumor
TM types of Chromagranina
Pheochromocytoma
Neuroblastoma
Carcinoid tumors
Small cell lung CA
Clinical utility of C-peptide
insulinoma affecting b-cells islet of langerhans = glucanoma. [glucagon]
Methods of:
HVA/VMA
Metanephrines
Catecholamines
5-HIAA & Serotonin
HPLC
HPLC
HPLC
LC-MS
MS
HPLC
Methods of:
Calcitonin
PTH
GH
PRL
ACTH
Cortisol
ADH
IA
Methods of:
Chromogranina
C-peptide
ELISA
RIA
ANTIGEN
_________– one of the 1st tumor markers discovered
- [+] fetal development; [-] as person grows
- When it is redected= ________.
[2] – expressed transiently during normal development and are then turned on again in the formation of tumors. _
___________were directly identified from human tumor extracts / cell lines. These are directed toward specific [2] and are best used for monitoring treatment of tumor that secrete these ______.
Oncofetal Ag
malignancy
CEA & AFP
Monoclonal defined Ag
CA
specific carbohydrates
epitopes
TUmor markers of Antigen
[4]
CA-19-9
CA 15-3
CA 27-29
CA 125
CA 19-9 tumor type + clinical utility
GI cancer
Adenocarcinoma
Pancreatic CA
CA 15-3 & CA 27-29 tumor type
Breast cancer
Metastatic carcinoma
CA-125 tumor type
Ovarian cancer
— used to classify tumors for therapy = Good TM
Prototypic examples of such a marker are [2]
Receptors
Estrogen
Progesterone receptor
UNDER RECEPTORS
Solid tumor biopsies [+] these markers → _________ is more likely to be effective.
_________ this receptor → will respond to chemotherapy
Tamoxifen chemoterapy
Breast cancer
Tumor markers of RECEPTORS
[4]
Estrogen receptor
Progesterone receptor
He-2/Neu
Epidermal GF receptor
Method used for all Antigen Tumor Markers
IA
Methods for Tumor markers:
Estrogen receptor
Progesterone receptor
He-2/Neu
Epidermal GF receptor
IHC
IHC
IHC, FISH, ELISA
IHC
— One of the oncofetal protein which decreases in adult levels [age: _______]
— Synthesized by the fetal ____.
Alpha-fetoprotein
7-10 months
liver
AFP is involved in regulating _______in the fetus.
when AFP is redetected during malignancy, it is classified as a _________ protein.
oncotic pressure
carcinoembryonic protein
AFP is increased in what conditions? [3]
Hepatocellular carcinoma/HCC
Germ cell tumors
Neural tube defects [Spina bifida]
AFP is decreased in what conditions? [3]
Down syndrome
Experts recommend AFP to be used in high risk developing _____ patients; patients with ________virus induced ________.
HCC
Hepa B/C
liver cirrhosis
AFP
[#] kD glycoprotein related to albumin
Upper normal limit: [#] ng/mL.
70
15
AFP
–Completely [specific/ not specific] with a sensitivity levels of: [2]
Not specific
40%-65%
80%-95%.
Major use of AFP is the classification and monitoring therapy of ________.
[2 TYPES]
Testicular CA
Seminomatous testicular CA
Nonseminomatous testicular CA
tumor formed directly from malignant germ cells; slow growing
Seminomatous testicular CA
Nonseminomatous testicular CA came from ______, and it spreads [slow/fast]. Differentiation [4]
other sources.
fast
Yolk sac tumors
Embryonal carcinoma
teratoma
choricarcinoma
Nonseminomatous testicular CA increased in AFP
Yolk sac tumors
Embryonal carcinoma
Nonseminomatous testicular CA increased in HcG
Choriocarcinoma
AFP Staging of Nonseminomatous testicular cancer
[3]
Stage 1: 10-20%
Stage 2: 50-80%
Stage 3: 90-100%
2 Methods of AFP
Automated IA
In serum/amniotic fluids
— a murine monoclonal antibody raised against a serous ovarian carcinoma cell line.
— expressed in the ovary, in other tissues of ______ duct origin [embryonic tissue] + human ovarian carcinoma cells.
CA-125
Mullerian
— ONLY CLINICALLY ACCEPTED SEROLOGIC MARKER OF OVARIAN CANCER but is [X] Specific.
CA 125
CA 125 levels w/ ovarian cancer stage:
▪ Stage I – increases by ___%
▪ Stage II – increases by ____%
▪ Stage III and IV – increases ____%
50%
90%
>90%
CA 125 is FALSELY [INC]: ewandi
E1D/EWANDI
Endometriosis
1st trimester of pregnancy
During menstruation
Methodology for ca 125
IA with the use of OC 125 + M11 Ab
Upper normal limit of CA 125
35 u/ml
— HMW mucin glycoprotein expressed by various adenocarcinoma especially those associated with the breast
CA 15-3
True or False
Carcinoembryonic Ag is more specific/sensitive than Metastatic Cancer
False
CA 15-3 is falsely increased in what conditions?
Chronic hepatitis
Liver cirrhosis
Sarcoidosisis
TB
SLE
Upper normal limit of CA 15-3
25U/ml
— glycoprotein produced only in the epithelial cells of the acini and prostatic ducts in the prostate.
Prostatic Specific Antigen
PSA is a serine protease of the _______ gene family and functionally regulates _____ fluid viscosity & instrumental in dissolving the_______ [protects egg cell] → allowing sperm to enter.
kalikrein
seminal fluid viscosity
cervical mucus gap
2 forms of PSA IN THE BLOOD:
1. ________– unbound
2. ________ – bound w/ [2]
Free
Complexed
a1-antichymotrypsin
a2-macroglobulin
FALSELY increased values of PSA:
Benign Prostatic Hyperplasia
Recent ejaculation & Direct rectal exam
Irritation
Prostate infection
Known interferences of PSA [FALSE NEGATIVE]
[2]
Hook effect
Human anti-animal Ab/HAMAS
METHODOLOGY:
IA: free + complexed PSA [both, if not, which one?]
Which is used?
a1-antichymotrypsin
OR a2-macroglbulin
Standard total cutoff: _____.
both
a1-antichymotrypsin
<4ng/ml
— HMW mucin indicator of pancreatic cancer
— Related to ______blood group substance
EXAMPLES: [2]
ca-19-9
lewis
Lea [a+, b-], Lea [a-,b+]
PSA INDICATOR: GLPC
— [INC] various adenocarcinoma:
Gastric
Lung
Pancreatic
Colorectal
GALUPAC
Gastric
Lung
Pancreatic
Colorectal
Upper Normal Limit is 37U/mL
CA 19-9
— Large heterogenous glycoprotein that is part of the Ig superfamily and is involved in apoptosis, immunity, cell adhesion.
Carcinoembryonic Antigen/CEA
— # used tumor marker for COLORECTAL CANCER and is also # [INC] Lung, Breast, and GI tumors
CEA
CEA is FALSE POSITIVE in what conditions?
HLCRA/hala sira
Heavy smoking
Liver damage
Chemoterapy
Radiation treatment
CEA
Half-life: ____ days
Upper Normal Limit:
Definitve Malignancy:
2-8 days
2.5-5 ng/ml
>10ng/ml
Methodology of CEA
[Assay] + use of ________.
essential that the same assay be used for _____ monitoring.
- monitored every ______ to detect recurrence and determine therapy efficacy.
IA + monoclonal anti-CEA antibodies
serial monitoring
2-3mos
— Major soluble protein of the
chromaffin granules
— catecholamine storage vesicle — released from adrenal medulla w/ catecholamines
Chromogranin A
Chromogranin A is an INDICATOR of what conditions:
[5]
Pheochromocytoma
Neuroblastoma
Peptide producing tumor
Pancreatic tumor
Small cell lung cancer
Carcinoid tumor
— localized in the nuclei of mammary & uterine tissue
Estrogen/Progesterone receptor
— GOOD TUMOR MARKER – small tendency of reoccurrence ← due to it being present.
Estrogen/Progesterone receptor [ER/PgR]
— Used to identify PX MOST LIKELY TO BENEFIT FROM ENDOCRINE THERAPY
— Px whom primary tumor is rich to this → after ________ → experience longer disease-free interval.
ER/PgR
mastectomy
Human Chorionic Gonadotrophin
— [#] kD glycoprotein consisting of [2] subunits.
— dimeric hormone normally secreted by _______ in the placenta to maintain the ________ during pregnancy.
45
alpha
beta
trophoblasts
corpus luteum
__________IT IS UNIQUE:
— Degraded into multiple fragments:
HCG
Free beta subunit
Hyperglycosylated form
Intact molecules
Nicked hCG
HCG [INC]
— _____ hCG: in malignancies — ______ hCG: nonseminomatous tumors
beta
free-beta
HCG INDICATOR + ELEVATED:
Trophoblastic tumor
Choriocarcinoma
Germ cell cancer [ovary,testes]
Gestational Trophoblastic disease
Gestational Trophoblastic disease of HCG is comprised of? [4]
choriocarcinoma
hydatid form mole
placental site
persisent/invasive gestational trophoblastic neoplasia
METHODOLOGY of HCG
_________ capture & tracer
Ab targeted toward epitopes in the [2] hCG.
________: most useful because they detect both intact hormone and free b-hCG
Monoclonal
beta subunits
intact hCG
Total beta HCG assays
APPLICATION & PATHOPHYSIOLOGY of HCG
Nonseminomatous testicular cancer → ________ [INC] in [#]% - [#]% of patients
In combination with _____ + _______ → diagnose subtypes of testicular cancer
free-beta HCG
60%
70%
AFP
Biopsies
Detected by Pregnancy Kits
HCG
— acidic metabolites of catecholamines
HMV & VMA
— Excreted in larger than normal amount in px w/ tumor originating from _______ [embryonic tissue]
HMV & VMA
neural crest
SQUAMOUS CELL CARCINOMA ANTIGEN (SCCA)
||INDICATIVE OF:
Squamous cell carcinoma:
[7 organs/body parts]
head
neck
esophagus
lung
renal failure
advanced cervical CA
anal canal
________ is increased in hematologic malignancies:
[4]
Lipid associated sialic acid in plasma
Leukemia
Lymphoma
Hodgkin’s lymphoma
Melanoma
— gamma subunit of an enolase isoenzyme in the glycolytic pathway
Neuron-specific enolase
NSE is an INDICATOR
of:
[2]
Neuroendocrine tumor Neuroblastoma [children]
NSE is increased in tumors originating from the neuroendocrine cell system:
[2 conditions]
insulinomas
glucanomas
NSE values is highest in these 2 conditions:
Small cell lung cancer/Oat cell cancer [LOS]
— low molecular weight protein
— part of constant L-chain of MHC locus Ag that is expressed on the surface of # nucleated cell.
— secreted by all nucleated cells
B2-microglobulin
What is the specific marker of B2 microglobulin?
high cell turnover [hich cell proliferation]
It is increased in solid tumor and inflammatory disorders like RA, SLE, Sjogren’s, and Chron’s disease
B2-microglobulin
B2 microglobulin is stable in serum or plasma?
In urine: ____pH [degrades slowly/rapidly]
Normal value:
serum
<6. 0
rapidly
0.9 – 2.5 mg/L
enumerate angiogenic factors
VEGF
alpha/beta FGF [acidic/basic fibroblast]
TGF alpha
Molecular dx for susceptibility
BRCA1/2
Adenomatous polyposis colin gene
when cell cycle is mutated what happens?
INC
genetic instability
cellular evolution
malignancy progression
EC stimuli [signal transduction]
Antigens
hormones
cytokines
C-erbB2
TGF B2
EGF
Nerve GF
apoptosis markers [3]
Bcl2
Fas ligand
P53
EGP/Oncogenes/ k-ras
Tumor suppresor/Cell Cycle regulators [3]
BRCA 1
Cyclins
P53
Adhesion molecules
selectins
integrins
Ig family
Loss of cell adhesion proteins
B-catenin
E-cadherin