Far

Eastern University – Nicanor Reyes Medical Foundation o AFP in GI cancer with metastasis but with normal liver
CD LEC – LAB DX: NEOPLASIA TESTING function
Dr. Dematera, MD - Heterophillic antibody
o Treated individuals apparently produce heterophillic
NEOPLASIA TESTING antibodies against murine antibodies that interfere with
Serum Tumor Markers many of the immunoassays for tumor markers

IDEAL SERUM TUMOR MARKERS ALPHA FETOPROTEIN (AFP)
- Elevated in the serum only patients with a malignant tumor - Major fetal serum protein and is also one of the major
- Not be elevated in the serum of disease-free individuals or of carcinoembryonic proteins
individuals with nonmalignant diseases - Transiently elevated during pregnancy and in many benign
liver diseases
CLINICAL APPLICATION - Currently offered for prenatal screening for neural tube
- Screening defects and, in conjunction with free beta hCG and
o Valuable if use is confined to populations at risk for the unconjugated estriol, for Down Syndrome
disease - Elevated AFP can be found in patients with primary
- Diagnosis hepatocellular carcinoma (HCC) and yolk-sac-derived germ cell
o Issue: Sensitivity and Specificity tumors (mainly endodermal sinus tumor)
§ Use multiple markers
§ Measure velocity and density ANGIOGENIC FACTORS
- Predicting Prognosis - Basic Fibroblast Growth Factor (bFGF)
- Treatment response - Vascular Endothelial Growth Factor (VEGF)
o Levels of a tumor marker after surgery indicate o Elevated serum VEGF in ovarian cancer patients
completeness of removal of the tumor, recurrence, or correlate with cancer differentiation, metastasis, and
the presence of metastasis shorter average survival time
o During chemotherapy indicate effectiveness of the drug o Elevated serum VEGF is associated with shorter survival
that guide the selection of the most effective drug for in renal cell carcinoma and colon carcinoma
each individual case
CARCINOEMBRYONIC ANTIGEN (CEA)
THREE SPECIFIC CLASSES OF TUMOR MARKER - Nonspecific marker of colorectal cancer
- Oncofetal Antigens o Can be elevated in breast, lung, and liver cancers
o Normally expressed during fetal development but do - Marker for monitoring colorectal cancer
not occur normally in the tissues or sera of children and - Increasing levels suggest disease progression
adults - Elevated CEA levels before resection of colon cancer may
o Alpha-fetoprotein (AFP) and carcinoembryonic antigen suggest a worse prognosis
(CEA) - Declining levels during therapy suggest response to therapy
- Proteins occurring in the epithelial cells
o Elevated in tissue and serum in adenosquamous and CA 15-3 AND CA 27.29
squamous cell carcinomas - Correspond to sequences of mucins called polymorphic
o CA-19-9, CA 125, and CA 15-3 proteins epithelial mucins (PEMs)
- Polypeptide hormones and specific enzymes - Overexpressed on the cell surfaces of malignant glandular cells
o Beta chain of human chorionic gonadotropin (Beta- (BREAST CANCER)
hCG), and the placental isoform of alkaline phosphatase - CA 15-3
(ALP), that become elevated in the serum of patients o Levels increase with higher stages of breast cancer stage
with specific tumors. o Predict adverse outcomes in breast cancer patients
o For monitoring the clinical course of patients with
RECOMMENDATIONS FOR ORDERING TUMOR MARKER TESTS metastatic breast cancer
- Never rely on the result of a single test - Sensitivity: CA 15-3 < CA 27.29
- When ordering serial testing, be certain to order every test
from the same laboratory using the same assay hit CA 19-9
- + + -
- Be certain that the tumor marker selected for monitoring - Related to Lewis blood group substances: Le (a b ) or Le (a b )
recurrence was elevated in the patient before surgery - Elevated in patients with colorectal cancer, gastric cancer, and
- Consider the half-life of the tumor marker when interpreting pancreatic cancer
the test result - CA 19-9 and CA 50
- Consider how the tumor marker is removed from or o Correlate in pancreatic cancer
metabolized in the blood circulation - CA 50 and CA 19-5
o CEA: liver diseases o Colon, pancreatic, and hepatocellular carcinomas
o B2M: kidney disease
- Consider ordering multiple markers to improve both the CA 125
sensitivity and the specificity for diagnosis - More than 80% of nonmucinous epithelial ovarian carcinomas
- Be aware of the presence of ectopic tumor markers - Most serous, endometroid, and clear cell carcinomas of the
o Poor prognosis or metastasis ovary

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 - HE 4 o inverse relationship with prostate cancer risk
o Human epididymis protein 4 (HE 4) expressed in the o differentiate BPH from prostate cancer
reproductive and respiratory tracts - PSAV
o Elevated in more than half of ovarian tumors that do o PSA difference divided by the number of years
not express CA 125 o 0.75 ng/year or greater is a strong predictor of cancer
o Risk of Ovarian Malignancy Algorithm (ROMA) with a specificity of 95%
§ Combined HE 4 and CA 125 - PSA Density
§ Predict the presence of a malignant ovarian mass o Ratio of total PSA to prostate gland volume
than other markers, with high sensitivity and o >0.15 indicate an increased probability of prostate
specificity cancer rather than BPH

CALCITONIN SUMMARY:
- May elevate in patients with increased bone turnover rate - CA 125
associated with skeletal metastasis o Ovarian Carcinoma
- Elevated in medullary carcinoma of the thyroid - CA 19-9
- Ectopically elevated in bronchogenic carcinomas o Pancreatic/Gastric Carcinoma
- CA 15-3, CA 549
HUMAN CHORIONIC GONADOTROPIN (HCG) o Breast Carcinoma
- Composed of noncovalently linked to alpha and Beta subunits - CA 72-4
internally linked by disulfide bonds o Gastric Carcinoma
- Synthesized and secreted by malignant and nonmalignant - HER2/NEU
trophoblast cells o Breast Carcinoma
- Test detects: - HCG
o Intact hCG (hCGn- partially degraded hCG) o Choriocarcinoma
o hCG alpha subunit - AFP
o hCG beta subunit o HCC
o hCG Beta core (residual hCG beta) - CEA
- Choriocarcinoma (hCG Beta subunit) o Colon, Pancreas
- Seminomatous testicular cancer (intact hCG, Beta hCG or free - PSA, PAP
alpha subunits in equal amounts) o Prostate
- Nonseminomatous cancers (hCG or Beta hCG subunits) - NSE
o SCCL, and neuroblastoma
HER2/NEU (C-ERbB-2) ONCOPROTEIN - TP53
- Elevated in the sera of patients with a number of different o many
epithelial cell cancers, including breast cancer
- Breast Cancer
o Very important prognostic and predictive marker
o Increased serum HER2/NEU before adjuvant therapy is
associated with increased tumor size, tumor grade, and
positive lymph nodes
o Serum HER2/NEU test is indicated for follow-up and
monitoring of patients with metastatic breast cancer
with initial serum level greater than 15 ng/mL
§ Continuously <15 ng/mL or less during the course
of disease àlonger survival
§ Higher levels predict incomplete response, while
low levels suggest longer or complete treatment
responses

SERUM PROSTATE-SPECIFIC ANTIGEN (PSA)
- Excellent (gold standard) biomarker cancer marker in prostate
cancer screening, diagnosis, prediction of cancer risk and
recurrence
- Annual PSA screening is recommended by both the AUA and
the ACS for all men over the age of 50
- Reference Range: 0-4 ng/mL
- Used to guide clinical decisions for further tissue biopsy
diagnosis à increased prostate cancer detection, especially in
young men
- BPH and acute prostatitis also caused elevated serum PSA
levels
- % fPSA = fPSA/tPSA x 100 Notes from Lecture PPT only, and other handouts

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