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