6. What Are Tumor Markers?
Tumor markers are metabolic products produced by tumor cells or related to
presence of tumor, found in body fluids or tissue or tumor surface of patients
with cancers’.
Tumor markers are substances that can be detected in higher-than-normal
amounts in the blood, urine, or body tissues of some patients with certain types
of cancer.
A tumor marker may be made by a tumor itself or by the body in response to the
tumor.
7. Tumour markers
Substance present in the tumour, produced by the tumour or by the organism as
a response to the presence of the tumour
Provide information about biological characteristics of the tumour
1 Qualitative determination – histopathologic, in the tunour tissue
2 Quantitative determination – in the serum or biological fluids, dynamic follow-up
9. History of Tumor Markers
1 30-ies of the 20th century – hCG (physiologically produced by placenta)
discovered in young men with testicular tumours (Zondek)
2 70-ies of the 20th century - α1-fetoprotein discovered in liver tumours in mice
(Tatarinov), later on described in human hepatomas (Abelev)
Further intensive research and their practical usage of markers in oncology and
prenatal diagnostics
11. A good tumor marker should
1 It should be highly sensitive
2 It should be highly specific
3 100% accuracy in differentiating between healthy individuals and tumor
patients.
4 Should be able to differentiate between neoplastic and non-neoplastic disease
and show positive correlation with tumor volume and extent.
5 It should predict early recurrence and have prognostic value.
12. A good tumor marker should
6 It should be clinically sensitive i.e. detectable at early stage of tumor.
7 Its levels should be preceding the neoplastic process, so that it should be useful
for screening early cancer.
8 It should be easily assayable and be able to indicate all changes in cancer
patients receiving treatment
15. BIOLOGICAL MARKER
Some tumor products are appropriate to the tissue of origin, but others are not
and are regarded as ectopic or inappropriate.
These products are known as “ biological markers”
17. Classification according to type of the molecule:-
1 Enzymes or isoenzymes (ALP, PAP)
2 Hormones (calcitonin, bHcg)
3 Oncofetal antigens (AFP, CEA)
4 Carbohydrate epitopes recognised by monoclonal antibodies (CA 15-3,CA 19-
9,CA125)
5 Receptors (Estrogen, progesterone)
6 Protein Markers
18.
19. Potential uses
1 Screening in general population
2 Differential diagnosis of symptomatic patients
3 Clinical staging of cancer
4 Estimating tumor volume
5 As a prognostic indicator for disease progression
6 Evaluating the success of treatment
7 Detecting the recurrence of cancer
8 Monitoring reponse to therapy
20. In order to use a tumor marker for screening in the presence of cancer in
asymptomatic individuals in general population, the marker should be produced
by tumor cells and not be present in healthy people.
However, most tumor markers are present in normal, benign and cancer tissues
and are not specific enough to be used for screening cancer.
22. 1. ENZYMES
1 Alkaline Phosphatase (ALP)- primary or secondary liver cancer, metastatic
cancer with bone or liver involvement.
2 Prostatic acid phosphatase (PAP) -prostate cancer, Increased PAP activity may
be seen in osteogenic sarcoma, multiple myeloma and bone metastasis of other
cancers and in some benign conditions such as osteoporosis and
hyperparathyroidism.
3 Prostate Specific Antigen (PSA)- much more specific for screening or for
detection early prostate cancer.
23.
24. 2. HORMONES
1 Calcitonin- medullary thyroid cancer
2 Human Chorionic Gonadotropin (hCG)- tumors of placenta, gestational
trophoblastic disease and some tumors of testes and ovary
25. 3. ONCOFETAL ANTIGENS
1 α-fetoprotein (AFP)- hepatocellular and germ cell carcinoma
2 carcinoembryonic antigen (CEA)- colorectal, gastrointestinal, lung and breast
carcinoma.
26. 4. CARBOHYDRATE MARKERS
1 CA 15-3-breast carcinoma may also be present in pancreatic, lung, ovarian,
colorectal and liver cancer and in some benign breast and liver diseases.
2 CA 125- ovarian and endometrial carcinomas, elevates in pancreatic, lung,
breast, colorectal and gastrointestinal cancer, and in benign conditions such as
cirrhosis, hepatitis, endometriosis, pericarditis and early pregnancy
3 CA19-9-colorectal and pancreatic carcinoma, elevated levels seen in
hepatobiliary, gastric, hepatocellular and breast cancer and in benign conditions
such as pancreatitis and benign gastrointestinal diseases.
27.
28. 5.RECEPTOR MARKERS
1 Estrogen and progesterone receptors are used in breast cancer as indicators
for hormonal therapy.
2 Patients with positive estrogen and progesterone receptors tend to respond to
hormonal treatment.
29. 6. PROTEIN MARKERS
1 Ferritin- Ferritin is a marker for Hodgkin lymphoma, leukemia, liver, lung and
breast cancer.
2 Thyroglobulin- It is a useful marker for detection of differentiated thyroid cancer.
3 Immunoglobulin- Bence-Jones protein is a free monoclonal immunoglobulin
light chain in the urine and it is a reliable marker for multiple myeloma
32. CA 125
1 Approx 90% of ovarian cancers are epithelial carcinomas and contain a
epithelium–related glycoprotein, cancer antigen 125.
2The major forms in serum have molecular weights of 200 kDa to 400 kDa.
3 Marked elevations (>1500 U/mL) are generally seen with ovarian cancer.
4 The ACOG and Society of Gynecologic Oncologists- recommend gyne-onco
referral for women with a pelvic mass suggestive of ovarian cancer and a serum
CA-125 value >35 U/mL in postmenopausal women or >200 U/mL in
premenopausal women.
33. Applications in ovarian cancer detection
Early detection of ovarian cancer through the measurement of CA-125,
usually in combination with other modalities (eg, bimanual pelvic
examination, transvaginal ultrasonography), is the most promising
application of this tumor marker, permitting effective triage of patients for
primary surgery.
34. Ovarian cancer screening using CA-125
1 Currently, ovarian cancer screening is not recommended for women with no risk
factors.
2 For women at increased risk ovarian cancer screening with CA-125 or TVS may
be considered.
3 Women at high risk such as those with mutations in ovarian cancer
susceptibility genes, should be screened by a combination of TVS and CA-125.
4 Limitation of CA-125 screening is that serum levels are elevated in only
approximately 50% of patients with stage I disease
37. Carcinoembryonic Antigen (CEA)
Glycoprotein antigen
Normal serum value: <2.5 ng/mL in nonsmokers;<5 ng/mL in smokers
t1/2: 1 to 7 days (depends on hepatic function)
Elevated in malignancies:-colorectal breast, pancreas gastric/lung cancers
Benign conditions:-Cigarette smoking (upto 19%),Peptic ulcer disease,
Inflammatory bowel disease Cirrhosis, biliary obstruction
CEA is used to monitor response to treatment, to detect recurrence early
38. Carcinoembryonic Antigen (CEA)
CLINICAL USES
1 Pre- operatively: values >7.5ng/ml associated with poor prognosis
2 Post-operatively: as measure of the completeness of tumor resection---
incomplete resection or occult metastases
3 Monitoring of tumor recurrence: Rising trend will predict recurrent disease with in
3-4 months-even if CT-scan is normal
4 Prognostic value: Over-all survival was decreased significantly when pre-
operative CEA was >5 ng/ml (except in advanced disease)
5 Moniter of tumor regression in metastatic disease
42. PSA
1 Glycoprotein secreted by prostatic acinar & ductal cells
2 Normal value: 2.5-4 ng/ml
3 t1/2: 2-3 days
4 Malignancies: elevated in prostate cancer.
5 Benign conditions: Benign prostatic hyperplasia (BPH), prostatitis, prostate
surgery, cystoscopy
43. PSA
5 Evated for at least 6-8 weeks after prostate biopsy
6 PSA is the only marker used to screen for a common type of cancer (although
some medical groups do not recommend its use) along with (and before) digital
rectal exam (DRE).
7 Highly marker for prostate cancer but less specific.
8 The PSA test is very valuable in assessment of response to therapy and follow-
up of patients with prostate cancer.
44. PSA
9 Blood PSA level below 4 ng/mL means cancer is unlikely and levels greater
than 10 ng/mL mean cancer is likely. The area between 4 and 10 is a gray zone-
prostate biopsy is recommended for a person with a level above 4 ng/mL
10 PSA level over time (PSA velocity- normal 0.04 ng/ml/year for age 60 yrs), an
increase from one year to the next may mean prostate cancer is more likely.
11 A helpful test when a PSA value is between 4 ng/mL and 10 ng/mL is to
measure the free PSA (or percent-free PSA). When the free PSA makes up more
than 25% of the total PSA, prostate cancer is unlikely. If the free PSA is below
10%, the chance of prostate cancer is much higher (about 50%).
Patients who have been treated with surgery or radiation therapy meant to
46. Lactate dehydrogenase
Serum LDH concentrations are elevated in 30 to 80 percent of men with pure
seminoma and in 60 percent of those with nonseminomatous tumors, also in
lymphomas
LDH is a less sensitive and less specific tumor marker than beta- hCG or AFP for
men with NSGCTs, but it may be the only marker that is elevated in seminomas.
In addition, a significantly elevated serum LDH has independent prognostic value
in men with advanced seminoma.
Serum LDH is neither a sensitive nor specific indicator of disease recurrence in
men with GCTs. As a result, it is not a useful serum marker to monitor for disease
relapse.
51. Alpha-Fetoprotein (AFP)
AFP is a 70 kDa glycoprotein homologous to albumin.
fetal serum protein synthesized by the liver, yolk sac, and gastrointestinal tract.
AFP is a major component of fetal plasma, reaching a peak concentration of 3
mg/mL at 12 weeks of gestation. Following birth, AFP rapidly clears from the
circulation, because its half-life is 3.5 days. AFP concentration in adult serum is
less than 20 ng/mL.
Physiological function- Appears to perform some of the functions of albumin in the
foetal circulation.
52. Alpha-Fetoprotein (AFP)
Malignancies with elevated levels
Mainly confined to 3 malignancies, i.e.
Non-seminomatous germ cell tumours (NSGCT) of testis, ovary and other sites.
Hepatocellular carcinoma (HCC).
Hepatoblastoma (in children, extremely rare in adults).
53. Alpha-Fetoprotein (AFP)
AFP may be occasionally elevated in patients with other types of advanced
adenocarcinoma.
Benign conditions which may have elevated levels- Hepatitis, cirrhosis, biliary
tract obstruction, alcoholic liver disease, ataxia telangiectasia and hereditary
tyrosinaemia.
56. Thyroid Cancer
Thyrocalcitonin ：
Produced by thyroid C cells and medullary thyroid cancer
normal: <100 ng/L or <29 p mole/L
Effective in screen patients with 1st degree relatives affected by medullary thyroid
cancer and multiple endocrine neoplasia type 2
57.
58. Cervical Sqamous Cell Carcinoma
Squamous cell carcinoma antigen (SCC)
Normal value:<2 ng/ml
Not sensitive enough for screening early :-
stage carcinoma
Prognosis, monitor
59. Tumor Markers - Recent Advances
Shortcomings of “conventional markers” lead to “advanced molecular techniques”
based on
1 Genetic hallmarks of malignancy rapidly determined
2 Tumor Molecular aberrations reflected in plasma/serum/body fluids
3 Extremely small amounts of nucleic acids can be measured (PCR, RT-PCR)
4. High resolution protein separation 2 D polyacrylamide gel electrophoresis
technology)Rapid identification of separated proteins (mass spectrometry)
Proteomics (study of proteins) feasible
61. Tumor Markers - Recent Advances
Genomics-The study of genes and their function.
Proteomics-The study of the full set of proteins encoded by a genome.
Molecular Classification of Circulating Tumor Markers
1 DNA markers
2 RNA markers
3 Protein markers
65. Sensitivity & Specificity
None of current markers 100% S &S
Current Approach to increase S & S
To improve on a currently used marker -
(free PSA-benign)
To discover and validate new markers
To use a panel of tumor markers
66. Case 1
A 35-year-old healthy male with a past history of cryptorchidism repaired at age 5
presented with painless enlargement of the left testis.A testicular ultrasound
examination revealed soft tissue mass without a cystic component.
What markers will you do?
1 AFP
2 HCG
3 LDH
4 All of the above
5 None of the above
67. Case 2
69 y male with long standing anemia & positive occult blood test presented with
right iliac mass.
The marker useful in the diagnosis is:-
A AFP E None of the above
B LDH
C CEA
D All of the above
68. Case 3
A 63 male presented with urinary hesitancy, frequency, and nocturia. Digital rectal
exam revealed a large, nodular, and rubbery prostate gland with focal hard regions.
Prostatic biopsies were performed.
The most useful marker is
A AFP E CA 125
B Alkaline phosphatase
C PSA
D CEA
69. Case 4
52-year-old former dancer goes to her internist because of vague abdominal pain
and a feeling of fullness. The physician notes abdominal fullness with a fluid
wave, consistent with ascites. He also performs a pelvic examination. A 10-cm
left adnexal mass is easily felt. The following marker is of prognostic use;-
A CA 125 E None of the above
B PSA
C CA 27.29
D PAP
72. Remember the following:-
Please remember the following points when ordering a serum tumor marker;
1 Never rely on a single test
2 Recommend a panel of markers
3 In serial testing, use the same lab with same assay kit
4 Consider the half life of the marker when interpreting the test result
5 Consider how the tumor marker is removed or metabolized from the blood
circulation
73. Conclusions
Tumor markers have changed the diagnosis and management of patients with
malignancies
They play a vital role in staging testicular cancers, screening for prostate cancers,
prognosis in colorectal cancers.
They are being evaluated in screening for HCC, epithelial ovarian cancers.
Further research is needed to refine the role of these markers in management of
cancer patients.
Recent advances in technology provide additional malignant tumor markers in the
immediate future
74. Video link
1 What is a tumor?
https://www.youtube.com/watch?v=qOAYkXDqSeI
2 Classification of Neoplasm Benign and Malignant
https://www.youtube.com/watch?v=PimyJxiWRb8
3TUMOR MARKERS
PART-1
https://www.youtube.com/watch?v=QDAikPKUsBQ
PART-
https://www.youtube.com/watch?v=h7_u7j7yFRw
