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serologic tumor markers

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serologic tumor markers

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TA M
SEROLOGIC TUMOR MARKERSE-Boats
TUMOR MARKER TUMOR ANTIGEN MAJOR
DISEASE/CANCER
▪ Any substance that is:
o Present in or produced by tumor itself Alpha- HCC; Germ cell tumor
o Produced by host in response to a tumor fetoprotein
o Used to differentiate tumor from normal tissue
o Detected in cell, tissue, or body fluids Oncofetal antigen Colorectal CA
▪ Quantitatively or qualitatively Pancreas
▪ By chemical, immunological or molecular CEA Breast
biological method Lung
o To identify presence of cancer Gastric
▪ Biochemical indicators of presence of tumors Tissue Breast
Polyclonal Ab polypeptide Colon
IDEAL TUMOR MARKER defined antigen Ovary
100% sensitive and specific PSA Prostate CA




:

o Only in patients with malignant tumors CA 15-3 Breast
▪ Show positive correlation with tumor volume & extent
Colorectal
o Proportionate to size of tumor
CA 19-9 Pancreatic
▪ If tumor is big, serum level of tumor Monoclonal Ab Biliary & Gastric
marker should be higher defined
CA 50 Colorectal
o Level should change in response to the tumor size
(complimentary) Pancreatic
▪ Become elevated in the serum of cancer patients at an early
stage CA 125 Ovaries, Endometrial
▪ Predict recurrence before they are clinically detectable Pancreatic
▪ Easily measurable and easily reproducible Oncogene
HOWEVER, No ideal tumor marker fulfills all the above criteria Breast
▪ Studies show that one or more cancer biomarkers are Erb-B-2 Ovarian
almost always present in the serum of patients with cancer Gastric
▪ Any circulating cell product can be used as a tumor marker Enzymes
o As long as it is related to any event during the Neuroendocrine
formation and/or growth Neuron-specific tumors
▪ Malignant transformation enolase Small cell lung CA
▪ Proliferation Medullary CA of TG
▪ Dedifferentiation Islet cell tumor
▪ Metastasis
Hormones
▪ The blood levels of serum tumor markers are determined
ACTH Small cell lung CA
by:
o Tumor proliferation Calcitonin Medullary CA thyroid
o Tumor volume B-hCG Choriocarcinoma
o Proteolytic activities in tumor cell Gastrin Islet cell tumor
o Release from necrotic cells Insulin
Receptors
TYPES OF TUMOR MARKERS
ER-PR Breast
▪ Tumor markers can be: EGFR NSCLC
o Tumor antigens
Used in
▪ Oncofetal antigen
diagnosis of CLINICAL APPLICATION
▪ Polyclonal Ab defined human
▪ Monoclonal Ab defined malignancies.
▪ Clinical utility of a tumor marker depends almost totally on
o Oncogenes the specificity and sensitivity of the tumor marker as well
o Enzymes as its intended clinical use
o Hormones o Pre-requisite: know sensitivity & specificity
o Receptors


shaweefa

, PSA ▪ Can be used as screening of prostate CA DIAGNOSIS
▪ Organ-specific but not cancer-specific ▪ Most TM level alone: insufficient to diagnose cancer
▪ Marker of prognosis and monitoring of therapy o Fail to distinguish malignant from benign disease
of breast cancer ▪ TM level may be elevated in benign
HER2/neu ▪ Cancer-specific but not tissue-specific conditions
▪ Not used in screening o Not elevated in every person with cancer
▪ Also increased in lung cancer & other epithelial (especially in early stages of the disease)
tumors o Many are not specific to a particular type of CA
→ “suggest”
SENSITIVITY ▪ Examples
▪ 100% sensitivity mean that the test can detect all patients • Presence of CA-125: strongly
with that particular type of cancer suggest ovarian cancer
▪ Measure TRUE POSITIVITY • Presence of CA 15-3: presence
of breast CA
▪ Not a diagnostic tool
o Used as adjunct test or complimentary sign to
clinical findings & medical imaging
SPECIFICITY o Ex: clinical hx and finding of cirrhosis +
▪ Measure of FALSE POSITIVITY = TRUE NEGATIVITY ultrasound mass in the liver & highly elevated
▪ 100% specific means that it will identify only the patients alpha-fetoprotein → hepatocellular carcinoma
with the specific type of tumor ▪ Recommendation:
o Not those with benign or non-malignant disease o to improve diagnostic yield → use multiple
markers

STAGING & PROGNOSIS
▪ The knowledge of tumor aggressiveness helps in the
However, there is no 100% specific nor sensitive specific. development of a proper therapy for the patient
o Detection of tumor markers highly suggest a
more rigorous and systemic treatment
SCREENING
▪ Pre-therapeutic level of certain TM can contribute a
▪ Testing for CA in people who have no symptoms of the prognostic factor because of links with:
disease o Metabolic activity
▪ Not recommended due to: o Tumor size
o Lack of desired sensitivity & specificity because o Invasion
most tumor markers are non-specific → might ▪ Allow doctors to adjust therapeutic strategy
cause unnecessary alarm or anxiety o For groups with risk of failure response to
o Not elevated in early stages therapy
▪ Exceptions: ▪ Examples:
PSA ▪ Most widely accepted marker (together with PSA HIGH: associated with high gleason score +
DRE) to screen prostate CA (pre-operative) lymph node status
▪ DRE – direct rectal exam NORMAL: respond better to therapy
\

BREAST TUMOR ER-PR (+): good prognosis
Eg.
HER-2-Neu & Ki-67 (+): poorer prognosis
Mild PSA level & associated w/ small prostate gland
-




– might indicate CA
Mild PSA level with large gland - BPH MONITORING TREATMENT & RECURRENCE
Alpha- ▪ Together with ultrasound scanning ▪ One of the most useful application
fetoprotein ▪ Screen HCC in endemic areas (eg. China – ▪ Serum level of TM reflects the:
liver CA) o Success of the surgery
o Efficacy of chemotherapy




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