23) Tumor markers Flashcards
Molecule may be a product of the malignant tissue, or it may be a substance produced by the body in response to the malignancy
tumor marker
Because most tumor markers are molecular forms that exist at some level in normal, benign, and malignant neoplasia, they are not…
specific enough to be used as a means of screening an asymptomatic population
t/f tumor markers are diagnostic for cancer
false; rarely
PSA is an exception
first tumor marker
BJ protein for MM
Alpha-fetoprotein (AFP) used to screen for hepatoma in…
a Chinese population that had a high prevalence of that disease
Prostate-specific antigen (PSA) used to screen…
men over 50 years
elevated tumor marker may confirm dx if pt has…
Signs and symptoms of the disease and risk factors for the disease
Serum levels of tumor markers are widely accepted as useful for…
monitoring treatment of diagnosed disease states
3 considerations to make when evaluating utility of tumor markers
- A single result should not be used to make or confirm a diagnosis.
- Values obtained from different manufacturers’ test kits cannot be used interchangeably.
- Physiology of the body must be taken into account when evaluating the significance of a tumor marker result.
criteria for an ideal tumor marker
- Easy and inexpensive to measure
- Specific to the tumor
- Direct relationship between blood levels of the marker and tumor mass
- Abnormal plasma level, urine level, or both
- Levels that are stable and not subject to aberrant fluctuations.
- If the tumor marker is present in plasma of healthy individuals, it should exist at a much lower concentration than that found in association with all stages of cancer.
Measure of how often the assay system detects the biomarker when the disease is present
sensitivity
Used to describe the probability that a laboratory test will be negative in the absence of disease
specificity
the probability that a disease is present when the test is positive or that a disease is absent when a test is negative.
predictive value
positive predictive value =
100(TP)/(TP + FP)
negative predictive value =
100(TN)/(TN + FN)
sensitivity =
100(TP)/(TP + FN)
specificity =
100(TN)/(TN + FP)
A measure of how often the assay system detects the biomarker when the disease is present
diagnostic sensitivity
The probability that a lab test will be negative in the absence of disease
diagnostic specificity
combining multiple modes of genomic analysis: gene- and exon-level expression, DNA variation, and copy number data to fundamentally improve our understanding of the disease
microarrays for cancer detection
Prior to 1950s, —— were the only tumor markers available
enzymes
alk phos sources
Liver, bone, intestine, and placenta
normal increased levels of alk phos
pregnant women
growing children
help differentiate source of elevated ALP
5’-nucleotidase
γ-glutamyl transferase (GGT)
ALP isoenzymes
Dimer consisting of 2 subunits: M and B and 3 isoenzymes
creatine kinase
CK-1 is elevated in…
small cell carcinoma of the lung
prostate cancer
Nonspecific, but elevated in liver, non-Hodgkin’s lymphoma, acute leukemia, nonseminomatous germ cell testicular cancer, seminoma, neuroblastoma, and others.
lactate dehydrogenase
It is a glycoprotein hormone secreted by the syncytiotrophoblastic cells of the normal placenta and consists of 2 subunits
B HCG
2 hCG subunits
- Alpha: Common to several other hormones including LH, FSH, and TSH
- Beta: Unique to hCG, and the 28-30 amino acids located on the carboxyl terminus are antigenically unique
the free ß-subunit is produced together with intact or whole hCG
early pregnancy
useful in detecting trophoblastic tumors and together with AFP to detect of nonseminomatous testicular tumors.
B hCG
For ——– tumors, you would need to test for total β -hCG
testicular
Can be used to screen for choriocarcinoma (rare cancer of the uterus) in women who are at high risk for the disease
B hCG
A clinically useful application is for monitoring the treatment and progression of trophoblastic disease
B hCG
Extremely high initial ß-hCG levels (>200,000-400,000 U/L) are considered to…
put patients at high risk for treatment failure.
“Total hCG” assays measures both…
the intact hCG and free ß-subunits
Hormone produced by the C-cells of the thyroid
calcitonin
Calcitonin normally secreted in response to an ——— in serum calcium from bone, thereby ——— the serum calcium level
increase
lowering
Patients with familial medullary carcinoma of the thyroid, an autosomal dominant disorder, will present with elevated …
calcitonin
Elevated in benign conditions: pulmonary diseases, pancreatitis, hypertension, pernicious anemia, Paget’s bone disease, and pregnancy.
calcitonin
Patients with small cell carcinoma (SCC) of the lung may produce ——- in significant quantity.
ProACTH
Produced by the fetal yolk sac and fetal hepatocytes
Levels rapidly decline at birth and healthy kids and adults have negligible or undetectable levels
AFP
Elevated in patients with hepatocellular carcinoma
AFP
Measuring both —– and —– can be useful in classifying and staging germ cell tumors.
AFP and hCG
AFP and hCG
- Yolk sac tumors
- Choriocarcinoma
- Embryonal carcinoma
- Teratoma
- ↑ AFP
- ↑ hCG
- ↑ both
- both normal
Neural tube defect screening includes ——- in the second trimester from the maternal serum
AFP
During pregnancy, maternal AFP levels increase from —– weeks of gestation to a peak of about —– mg/L during the third trimester.
The fetal AFP reaches a peak of —– mg/L at 14 weeks and then declines to about —– mg/dL at term.
12
500
1000
70
leading causes of cancer in men
- skin
- prostate
Also referred to as human kallikrein 3 (hK3)
PSA
Serine protease consisting of 237 amino acid residues and 4 carbohydrate side chains
PSA
In seminal fluid, 60-70% as free PSA and <5% is complexed with protease inhibitors such as…
protein C inhibitor (PCI)
In blood, 55-95% of immune detectable PSA is bound to ——- and 5-45% of immune detectable PSA is free
α1-antichymotrypsin (ACT)
α1-antichymotrypsin (ACT)
Protein C inhibitor (PCI)
α1-proteinase inhibitor (API)
α2-macroglobulin (AMG)
form stable 1:1 complexes with PSA in serum
Measuring serum biomarkers for early detection of ——- cancer is a highly controversial topic in medicine
prostate
PSA testing by itself is not effective in the screening or detection of early prostate cancer because…
PSA is specific for prostate tissue, but not for prostate cancer
high PSA; benign condition
Benign Prostate Hypertrophy (BPH)
A widely used cutoff value representing low risk of disease for tPSA is —— ng/mL.
≤ 4.0
great likelihood of prostate cancer
PSA >10 ng/mL
% fPSA =
100(fPSA)/tPSA
% fPSA ——– detected 95% of prostate cancer when the tPSA is between 4 and 10 ng/mL
≤ 25%
advantage to complex PSA assay
minimal effect on the levels of cPSA after prostate manipulation either by flexible cystoscopy or digital rectal examination (DRE)
Most cPSA assays measure only…
PSA-ACT
The amount of —————- found in seminal fluid is about 100,000 fold higher than in serum
Human glandular kallikrein 2 (hK2)
Measuring serum ——— alone or in combination with tPSA/fPSA has been shown to be a significantly better predictor of organ-confined prostate cancer
hK2
May be better as detecting prostate cancer and reducing the number of unnecessary biopsies than fPSA
Useful when tPSA is in the range of 2.5-4.0 ng/mL
ProPSA
Primary form of proPSA found in tumor extracts
(-2) ProPSA.
encodes an mRNA elevated in prostate cancer
elevated urine levels increase diagnostic specificity
PCA3
PCA3 cutoff value
35
(increased likelyhood for positive biopsy)
Useful for early detection of prostate cancer
Early prostate cancer antigen-2 (EPCA-2)
CA 15-3
most widely used for breast cancer
Used for monitoring therapy for advanced or recurrent breast cancer
CA 15-3
Breast cancer oncogene identified as a transmembrane protein of the tyrosine kinase receptor family
Human epidermal growth factor receptor 2 (HER-2/neu)
Neu portion refers to its association with neural tumors
A useful prognostic indicator of overall survival in patients with breast cancer
Human epidermal growth factor receptor 2 (HER-2/neu)
humanized monoclonal AB against HER-2/neu receptors
Herceptin® (trastuzumab)
genes that predispose pt to develop breast and ovarian cancer because of an autosomal dominant trait
BRCA1 and BRCA2
Women who carry ——- mutations have a lifetime risk of breast cancer that ranges from 56-87% as well as an increased risk for developing ovarian cancer
BRCA1
Men with ———– mutations are at risk for male breast cancer and may also have an increased risk for developing various types of cancers including prostate, melanoma, and pancreatic
BRCA1 or BRCA2
It is a useful marker for recurrence of breast cancer in patients after initial therapy followed by adjuvant therapy
CA 549
NOT useful in detecting early breast cancer because of the high proportion of women with breast cancer having low levels
CA 549
detected by a monoclonal antibody is produced against an antigen in ascites fluid of patients with metastatic breast cancer.
CA 27.29
Useful in checking for recurrence with stage II or stage III breast cancer.
CA 27.29
Approximately 90% of ovarian cancers are ——- tumors.
epithelial
most common cause of cancer death from gynecologic tumors in the United States
ovarian cancer
Expressed by epithelial ovarian tumors and other pathological and normal tissues of mulerian duct origin
CA 125
Most useful for epithelial ovarian cancer (EOC) and endometrial carcinomas
CA 125
EosinophI-derived neurotoxin (EDN)
COOH-terminal osteopontin fragments
Correlates with ovarian cancer
cytokines IL-6, IL-8, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF)
ovarian cancer
hK5, hK10, and hK11
kallikreins associated with ovarian cancer
Plasmenyl Phosphatidic acid (PPA)
Plasmenyl Ethanolamine (PPE)
plasmalogens associated with ovarian cancer
Elevated levels of ——— were found in ascites of ovarian cancer patients but also in the corresponding plasma samples
Lysophosphatidic acid (LPA)
One of the easiest and simplest tests to perform for detecting colorectal cancer in the early stages, particularly for people older than age 50
fecal occult blood
found in embryonic tissue and elevated in colorectal cancer
Carcinoembryonic antigen (CEA)
CEA function
monitor therapy and detecting recurrence of colon cancer
NOT for screening
Expressed in the brush border membrane of intestinal mucosal cells
Associtaed with colon cancer
Guanylyl Cyclase C (GC-C)
Whole blood GCC-B1 test method
PCR
CA 19-9
CA 50
CA 242
pancreatic cancer markers
Glycoprotein that is a sialylated derivative of the Lea blood group antigen
CA 19-9
May be a good predictor of prognosis in pancreatic cancer
CA 19-9
Also known as gastrointestinal cancer-associated antigen (GICA)
CA 19-9
Monoclonal antibody developed against the human colonic adenocarcinoma cell line COLO 205.
CA 50
Has a higher percentage elevation in colorectal cancer than CA 50 and CA 19-9.
CA 242
most common type of bladder cancer
transitional cell carcinoma (TCC)
Can be found in urine due to invasion of the basement membrane by tumors or production by the tumor itself or a combination of these processes.
Bladder tumor antigen (BTA)
part of the internal structural framework of the nuclei of cells in the bladder
Nuclear matrix proteins (NMP)
Has been recommended for the differential diagnosis of small cell lung cancer
Neuron-Specific Enolase (NSE)
Can provide useful information in diagnosing non-small cell lung carcinoma (NSCLC).
Most sensitive biomarker in NSCLS, particularly small cell carcinoma (SCC).
CYFRA 21-1
intermediate filament keratins found in the intracytoplasmic cytoskeleton of epithelial tissue
Cytokeratins
elevated in lung cancer
may be used in the differential diagnosis of NSCLC, especially when used in combination with CYFRA 21-1 and CEA
Small Cell Carcinoma Antigen (SCCA)
Most potentially useful biomarker for gastric cancer
CA 72-4
Used to diagnose gastric cancer and monitor immunotherapy
CA 72-4 or Tumor-associated glycoprotein (TAG-22)
sensitivity of 41% in gastric cancer patients
B hCG
combinations of…
C A 242
C A 125
C A 15-3
C A 19-9
can help diagnose…
gallbladder cancer
disease is present
need true positives and false negatives
sensitivity
disease is absent
need true negatives and false positives
specificity
