Tumor Marker Flashcards
1
Q
Prognostic-
Predictive-
A
- predicting survival rate
- predict rxn to therapies
2
Q
Serum proteins-
A
Nonspecific malig, indicate infl
Acute- CHAB (c-reactive protein, haptoglobin, alpha 2 macro, beta 2 micro)
Chronic- hyperbilirubinemia
3
Q
Ectopic H
A
Travel in blood, could be paraneoplastic
PTH, GH, ACTH, TSH, HCG-beta
4
Q
Hormone receptors
A
On cell surface, in cytoplasm-> can change cell behavior
Estrogen, progesterone( breast cancer)
5
Q
Oncofetal antigen
A
CEA-> not sen spi early cancers
Alpha- feto protein
6
Q
CEA
Produced by mucin secreting glandular epithelium
A
Useful w- colorectal, pancreatic, lung, gastric, breast
7
Q
CEA
Benign situations
A
HIS AC
Smoking, IBD, Alcoholoc Cirrhosis, hepatitis
8
Q
Alpha feto protein->Screen high risk popul
Made by:
A
Made by yolk sac, fetal liver, fetal GI, little in adult liver
9
Q
Alpha feto protein
Useful w:
A
Liver, germ cells(testis), dec w lung, colon, pancreas
10
Q
Alpha feto protein
Benign situ:
A
Liver- cirr,necr,hepa
Pregnancy,
Neural tube defects
11
Q
ALP
A
- building bone(osteoblastic)
- effects bone, liver, placenta, intestine, regan
12
Q
ALP
Benign sit:
A
Pregnancy, childhood, obstructive liver ds, hepatitis, pagets, fracturer
13
Q
Breast
A
CEA, CA-27-29, CA-15-3
14
Q
Tumor markers: produced by
A
Mal + benign
Inc ds state
Inc spec sen
15
Q
Acid phosphatase
A
- breaking bone (osteoclasts)
- effects bone, prostate, erythrocyte, platelets
16
Q
Acid phosphatase
Benign sit:
A
BPH, mech trauma
17
Q
PSA (prostate specific antigen)
Made by prostate (B or M)
Small amt- normal
A
Inc level= inc tumor size; advanced
->BPH, inflam, trauma
18
Q
Best to ID recurrence
A
PSA
19
Q
PSA
Treatment
A
> 4ng/ml= biopsy, but
20
Q
CA 125
Useful w
A
Pancreatic, endometrial, ovarian
21
Q
CA125
Benign w
A
POUR End
Pregnancy, ovarian cysts, uterine, recurrence monitor, endometriosis
22
Q
CA 15-3
Useful w
A
Breast LEGO
Advanced breast, lung, endomet, GI, ovary
23
Q
CA 15-3
Benign w
A
Pets help
Pregnancy, TB, sarcoidosis
Hepatitis, endometriosis, lupus, pelvic inflam
24
Q
CA 27-29
Useful w
Only renal
A
Breast, colon, hepatitis, Group
Breast, colon, hepatitis
Gastric, renal, ovarian, uterine, pancreas
25
CA 19-9
Useful w
Colon, pancreas, biliary
Good for monitoring therapy in advanced cancer
26
Lung
CEA, CA 27-29, CA 15-3, alpha feto
27
Liver
Alpha feto, CA 27-29, CA 19-9
28
GI
CEA, CA 27-29, CA 15-3
29
Tumor Markers
• produced by malignant cells or by benign cells in response to the presence of malignancy
• May be applied to the detection, identification, monitoring, radiolocation, and therapy of malignancies
30
Where Found
• May be found in body fluids, tissue, or tissue extracts
31
General Principles
• Sensitivity and specificity of tumor markers typically improves in advanced disease
• Few are applicable for screening high risk groups
• Not yet useful in screening the general population
32
Use of Tumor Markers
* Detection
• Confirmation and diagnosis
• Detecting recurrence or metastasis
* Monitoring response to therapy
• Aid in choice of therapy
33
Use of Tumor Markers
Prognostic markers:
• Prognostic markers:
– Generally used to describe molecular markers that predict disease-free survival, disease specific survival, and overall survival
• Predictive markers:
– Used in the context of predicting response to certain therapies
• Often used interchangeably
34
Important Facts to Know
• Typically, should not rely on the result of a single test
• When ordering serial tests—use the same lab
• Be sure the marker you are studying was elevated prior to surgery
35
Important Facts to Know
• Know the T(1/2) of the marker when interpreting test results
• Know how the marker is removed or metabolized
• Use multiple markers when possible
– Increase sensitivity and specificity
• Nonspecific markers
– Cost saving, possible increase in sensitivity
36
Types of Tumor Markers
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Serum Proteins or Molecules
Enzymes
Ectopic Hormones
Oncofetal Antigens
Cellular Markers
Antigens Hormone Receptors
```
37
Serum Proteins or Molecules
Many are indicative of host injury and response
– Hyperbilirubinemia
– C-reactive protein
– Haptoglobin
– Alpha 2-macroglobulin
– Beta 2 microglobulin
38
Serum Proteins and Molecules
• Nonspecific for malignancy
• Typically indicate inflammatory response
– Chronic or acute
39
Ectopic Hormones as Tumor Markers
Characteristics:
• Secreted by tumor cells into circulation
• Functionally identical to the native hormone
• Produce clinical syndromes (paraneoplastic)
• Assayed in serum
40
Ectopic Hormones (Partial List)
• PTH (parathyroid hormone)
• GH (growth hormone)
• ACTH (adrenocorticotrophic hormone)
• TSH (thyroid stimulating hormone)
• HCG-β subunit (human chorionic gonadatrophin)
41
Hormone Receptors
* Receptors are found on the cell membrane or in the cytoplasm
• Functional, can modify tumor behavior
* Assayed in tissue, not in serum
42
Hormone Receptors
• Estrogen
• Progesterone
– Primarily used in breast cancer
43
Oncofetal Antigens
Carcinoembryonic Antigen Alpha-fetoprotein
44
Oncofetal Antigens
• Produced by fetal cells during development but not normally produced by adult cells
• Produced by tumor cells by “de- differentiation”
• Used primarily to detect recurrence and metastasis, to follow the response to therapy, and to assess prognosis
45
CEA
• Characteristics
– Glycoprotein produced by mucin-secreting glandular epithelium in the fetus
46
CEA
Left gas pan chicken breast
• Useful as a tumor marker in:
| – Colorectal carcinoma
– Pancreatic carcinoma
– Lung cancer
– Gastric cancer – Breast cancer
47
CEA
• Elevated in 60 –90% of colorectal carcinomas
• Best used in monitoring postoperative/post- treatment recurrence
– Levels rise with recurrence and metastatic disease
– Levels fall with decreased tumor burden
• Most cost-effective approach for detecting metastatic disease
48
Benign Conditions with Elevated CEA
His AC
• Cigarette smokers
• Inflammatory bowel disease
• Alcoholic cirrhosis
• Hepatitis
• Lack both specificity and sensitivity to detect early cancers
49
Alpha-fetoprotein
• Characteristics:
– Glycoprotein
– Predominate component of serum proteins in early embryonic life
– Synthesized by fetal yolk sac, fetal liver, fetal gastrointestinal tract, and in minute amounts by the adult liver
50
AFP
• Useful as a tumor marker in:
– Hepatocellular carcinoma
– Germ cell tumors of the testis
– Less regularly in carcinomas of the colon, lung, and pancreas
51
AFP
• Hepatocellular Carcinoma
– Elevated in 60-75%
• False Positives
– Cirrhosis
– Massive liver necrosis
– Acute and Chronic hepatitis
– Normal pregnancy
– Fetal neural tube defects
52
AFP
• Considered to be sensitive and specific enough to be used to screen for
HCC (hepatocellular carcinoma) in high risk populations
– Hepatitis B carriers
53
Enzymes
• May be present in several tissues
• Most enzymes have structurally similar isotopes
• Assayed in the serum
• Released into circulation with increased cell turnover
54
Clinically Useful Enzymes
• Alkaline phosphatase • Acid phosphatase
55
Alkaline Phosphatase (ALP)
• Characteristics
– Several isoenzymes:
Bone, liver, placenta, intestine, and regan
• As a tumor marker
– Osteoblastic lesions
– Derived from the tumor itself
56
ALP
• Benign Conditions Causing Elevated Levels
– Pregnancy (normal)
– Childhood
– Obstructive hepatic disease
– Hepatitis
– Paget’s disease
– Fractures
57
Acid Phosphatase (ACP)
• Characteristics
– Numerous isoenzymes
– Bone, prostate, erythrocytes, platelets
• As a tumor marker
– Prostate carcinoma (from the prostate tissue/tumor)
– Bone
—osteolytic metastasis
58
ACP
• Benign conditions with elevated levels
– Benign prostatic hyperplasia
– Mechanical trauma
• Accidental
• Instrumentation
59
Antigens as Tumor Markers
Prostate Specific Antigen
| CA 125
CA 15-3
CA 27-29
CA 19-9
60
Prostate Specific Antigen (PSA)
• Serine protease-cleaves and liquefies seminal coagulum after ejaculation
• Produced by prostate epithelial cells
– Both benign and malignant
• Normally, minute amounts circulate in the blood
61
PSA
• Increased levels occur with localized as well as advanced disease
• PSA levels are proportional to the volume of tumor
• Also raised in BPH, inflammation, and trauma
• Complexed PSA is elevated in prostate cancer, better than total PSA
62
PSA
• The test has both a low sensitivity and specificity
* There is no PSA level that ensures that the patient does not have prostate cancer
* Best use:
– Detecting residual disease or recurrence following treatment for prostate cancer
63
PSA—What are the Problems?
• Total serum PSA levels of 4 ng/mL are used as the threshold for doing a biopsy
– Yet 20-50% of patients with clinically significant prostate cancers have values
64
PSA—What are the Problems?
• Many prostate cancers do not cause clinical problems
– “Die with not of”
• Curative treatment (radical prostatectomy) of cancer confined to the gland is associated with morbidity and mortality
– 50% report permanent sexual dysfunction
– 25% will report some degree of incontinence
65
PSA—What are the Problems?
• Of 1,000 men with symptomatic prostate hyperplasia:
– 400 will have elevated PSA levels or abnormal rectal exams
– 30 of these will have prostate cancer
66
CA 125
• A high-molecular-weight antigenic determinant on a glycoprotein shed into the bloodstream by malignant cells derived from malignant cells derived from coelomic epithelium
• Increased in patients with ovarian, endometrial, pancreatic, and other cancers
• May be elevated in benign conditions:
– Early pregnancy, endometriosis, uterine leiomyoma, and benign ovarian cysts
67
CA 125
• Although elevated levels are associated with an increased risk of ovarian cancer, 6% of normal women have similar levels
• Can be used to monitor recurrence
68
CA 15-3
• Is an epitope of a large membrane glycoprotein encoded by the MUC1 gene that tumor cells shed into the bloodstream
• Most useful in following the course of treatment in women with advanced breast cancer
• Levels infrequently elevated early in the course of the disease
69
CA 15-3
• Can be elevated in cancers of the:
– Lung
– Ovary
– Endometrium
| – GI tract
70
CA 15-3
• Can be increased in benign conditions such as:
– Chronic hepatitis
– TB
– Sarcoidosis
– Pelvic inflammatory disease
– Endometriosis
– Systemic lupus erythematosus
– Pregnancy and lactation
71
CA 27-29
• Can be elevated in breast, colon, gastric, renal, lung, and ovarian, pancreatic, uterine and hepatic carcinoma
• Benign conditions with elevations include 1st trimester pregnancy, endometriosis, benign breast disease, renal disease, and hepatic disease
72
CA 27-29
• Current best use: monitor patients during active therapy (together diagnostic imaging and history and physical exam)
73
CA 19-9
• Produced by colon, pancreatic, and biliary cancers
• Not useful for screening, diagnosis, surveillance, or monitoring for colon or pancreatic cancer
• May have a role in monitoring therapy in patients with advanced cancer
