Tumor Marker SGCC 2009 Final

Role of Tumor Marker in
Gynecolgic Malignancies
Solo Gynecologic Cancer Conference

TUMOR MARKER
Definition:
A tumour marker is a
biochemical indicator selectively
produced by the neoplastic
tissue and released into blood
and detected in blood or in other
body fluids.
SGCC 2009
SOLO GYNECOLOGIC CANCER CONFERENCE 2009
Tumour Markers: - Classification
Class 1: -
Antigens unique to a neoplasm not shared by
other tumours of same histological type .
Class 2: -
Antigens expressed by many or most tumours of a
specific histological type and of other histological
type,
But not expressed by normal adult tissue.
Class 3: -
Antigens expressed by both cancer and normal
adult tissue.
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Clinical Use of Tumor Marker
Screening
Diagnosis
Monitoring therapy
Remission
Follow-up
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When is a Marker Clinically Useful?
It is either prognostic or predictive
The magnitude of effect is sufficient
Clinical decision result in acceptable outcomes
Greater chance for benefit
Smaller toxicity risk
Assay is reproducible
Clinical trial/marker study design is appropriate
Results are validated in subsequent well-
designed studies
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Ideal Tumor Markers
Be specific to the tumor
Level should change in response to tumor size
An abnormal level should be obtained in the

presence of micrometastases
The level should not have large fluctuations that are

independent of changes in tumor size
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Ideal Tumor Markers
Levels in healthy individuals are at much lower
concentrations than those found in cancer patients
Predict recurrences before they are clinically

detectable
Test should be cost effective
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True tumor status
Tumor marker ____________________________
Result Positive Negative
__________________________________________________________________
Positive a b
(True positive) (False positive)
Negative c d
( False negatives) (True negatives)
__________________________________________________________________
__
Sensitivity = true positives / all with tumor = a /a + c
Specificity = true negatives / all tumor free = d / d + b
PPV = true positives / all with positive tumor marker results = a / a + b
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Specificity in Tumor Markers
Tumour specific proteins

Expressed only in tumour cells
Fusion proteins in Philadelphia chromosome in CML
Non-specific proteins related to malignant cells

Oncofetal antigens (carcinoembryonic antigen)
Fetoprotein (hepatocellular, testicular & ovarian ca)
Cell specific proteins overexpressed in malignant cells

Expressed normally by differentiated cells but are expressed at
higher rates in the corresponding tumour cells
Prostate specific antigen (PSA) in prostate ca
SGCC 2009
Clinical Use of Tumor Marker:
Screening
The natural history of the cancer should be

understood
Effective treatments must be available
The test must be acceptable to both patients
and physicians
The test must be safe and relatively
inexpensive
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Screening
Screening tests require high sensitivity to

detect early-stage disease
These tests also must have sufficient

specificity to protect patients with false-
positive results from unwarranted diagnostic
evaluations
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Interpreting
Tumor Marker Tests
Never rely on the result of a single test

Order every test from the same laboratory
Consider half-life of the tumor when
interpreting the result
Consider how the Tumor Marker is removed
or metabolized
SGCC 2009
Some Key Facts
Lack of specificity
Cancer heterogeneity
False negatives
Benign diseases positive CA 125 or
CEA
Smokers have raised CEA
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Diagnosis
Tumor markers
are neither sensitive nor specific for
the diagnosis or exclusion of cancer
SGCC 2009
Monitoring Therapy
Early rise: due to cell lysis, not treatment failure

Consistent increase: treatment failure
Residual elevation: persitent disease
Fall usually means response
Beware heterogeneity
“Normal” does not usually mean remission
Palliative therapy – treat the symptom
or the number?
There is a role for clinical judgement !
SGCC 2009
Gynaecological Tumour Markers
1. Human Chorionic Gonadotrophin (HCG)

2. Alfa Feto Protein (AFP)
3. Cancer Antigen-125 ( CA125)
4. CA 19-9
5. Carcino Embryonic Antigen (CEA)
6. Placental Alkaline Phosphtase (PLAP)
7. Squamous Cell Carcinoma Antigen
(SCCA)
8. CA15-3, ( Also known as HER-2neu,
OVX1, OVX2).
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• Macrophage Colony Stimulating Factor
(MCSF)
• Tumour Associated Trypsin Inhibitor
(TATS)
• Galactosyl Transferase Associated with
Tumour ( GAT)
• Alfa Amylase
• Lactate Dehydrogenase (LDH)
• Tumour Associated Glycoprotein-72 (TAG-
72
• Estrogens, Progesterone, Androgen
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Tumor Markers
in Ovarian Germ Cell Tumors
TUMOR HCG AFP LDH CA-125
Mixed germ cell tumor + + + +

Embryonal carcinoma + +  +
Endodermal sinus tumor - +  ?
Dysgerminoma  - + +
Immature teratoma -   +
Choriocarcinoma + -  ?
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Lysophosphatidic acid ( LPA )
Found in the ascitic fluid of patients with ovarian cancer

and is associated with ovarian cancer cell proliferation.
Plasma LPA concentrations were elevated in 90% of

patients with stage I disease and 100% of patients
with advanced and recurrent disease.
CA125 concentrations appeared to complement LPA
levels.
SGCC 2009
HER-2/neu (c-erbB-2)
In ovarian cancer, 9% to 38% of patients have

elevated levels of p105, the shed extracellular
domain of the HER-2/neu protein
Its main use is as a predictor of prognosis
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Tumour Markers Produced by Epithelial
Ovarian Tumours
TUMOUR PERCENT OF TUMOURS
PRODUCING MARKERS
CA125 CA19-9 CEA PLAP
SEROUS: -
Benign 80 6 0 83
Borderline 100 87 6 100
Malignant 100 40 17 84
MUCINOUS: -
Benign 0 73 45 0
Borderline 12.5 87 87 0
Malignant 16 86 97 0
ENDOMETROID CA 66 64 25 66
CLEAR CELL CA 75 70 15 0
UNDIFFERENTIATED 82 52 23 57
MIXED MULLERIAN tumour 80 80 40 33
Cancer Antigen 125 (CA 125)
Is elevated in > 80% of advanced EOCs

Is elevated in 25 - 50% of Stage I cancers
Mucinous tumors don’t express CA125
Elevated in many non-cancerous
conditions
Poor specificity: especially in
premenopausal
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NOT a screening test for the general population
50% at 2nd look laparotomy with residual disease had
negative CA 125
11,283 women screened, 486 laparotomies,
to detect 5 invasive ca and 8 borderline tumors
Ovarian Ca probable in post-menopausal with an
asymptomatic pelvic mass and CA-125 > 65 U/mL
(sensitivity = 97%, specificity = 78%)
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CA125 is recommended as an adjunct
in distinguishing benign from
malignant pelvic masses, particularly
in postmenopausal women
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Post-menopausal women with ovarian
masses.
Sensitivities: 71–78%, Specificities: 75–
94%
CA125 >95 U/mL in post-menopausal
women can discriminate malignant
from benign pelvic masses with a PPV
of 95%
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Cancer Antigen 125
Monitoring Treatment Response
There is general consensus among current
guidelines in recommending that CA125 be used
to monitor therapeutic response
Serial measurement of CA125 may also play a role in

monitoring response to chemotherapy
Declining CA125 correlate with treatment response
In a meta-analysis, serial CA125 concentrations in 89% of 531
patients correlated with clinical outcome of disease
SGCC 2009
Cancer Antigen 125
Prognosis
CA125 is recommended during primary therapy as
a potential prognostic marker
After primary surgery and chemotherapy persistent

elevations indicate a poor prognosis
Pre-operative CA125 level >65 U/mL:

- significantly lower 5 ysr
- 6.37 x risk of death compared with < 65 U/mL
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The half-life of the CA125 marker indicates
prognosis after chemotherapy.
A half-life of < 20 days was associated with

significantly improved survival (28 m vs. 19 m) as
compared to > 20 days
Improved survival also correlates with normalization

of CA125 after three cycles of combination
chemotherapy.
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CA-125: - in Endometriosis
In minimal to mild endometriosis serum CA125 level is
normal but in moderate to severe endometriosis the level
rises.
In normal person with out endometriosis level is : - 8 to 22
u/ml (non-menstrual phase)
In minimal to mild endometriosis level is: - 14 to 31 u/ml
(non-menstrual phase)
In moderate to severe endometriosis level is: - 13 to 95
u/ml (non-menstrual phase)
The specificity in endometriosis is about 80%
The sensitivity is around 66%.
If the ratio during menstrual phase to follicular phase is
more then 1.5, then it is a better sensitive marker.
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Tumor Marker Ca Endometrium
Ca 125 : Stadium dini : 0-20 %

Stadium IV : 66 – 78 %
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Tumor Marker : - Ca Cervix
Produced mainly by Sq.Cell Ca. of Cx, Vagina & Vulva
SCC : * 57 – 66 %
* 72 – 95 % correlation Respon
SCC Level
Levels become highest if there is metastasis
SGCC 2009
Terima kasih
SGCC 2009

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Role of Tumor Marker in

Solo Gynecologic Cancer Conference

Level should change in response to tumor size

An abnormal level should be obtained in the

The level should not have large fluctuations that are

Predict recurrences before they are clinically

Test should be cost effective

Tumour specific proteins

Non-specific proteins related to malignant cells

Cell specific proteins overexpressed in malignant cells

The natural history of the cancer should be

Screening tests require high sensitivity to

These tests also must have sufficient

Never rely on the result of a single test

Early rise: due to cell lysis, not treatment failure

There is a role for clinical judgement !

1. Human Chorionic Gonadotrophin (HCG)

Mixed germ cell tumor + + + +

Found in the ascitic fluid of patients with ovarian cancer

Plasma LPA concentrations were elevated in 90% of

In ovarian cancer, 9% to 38% of patients have

Is elevated in > 80% of advanced EOCs

Serial measurement of CA125 may also play a role in

After primary surgery and chemotherapy persistent

Pre-operative CA125 level >65 U/mL:

A half-life of < 20 days was associated with

Improved survival also correlates with normalization

Ca 125 : Stadium dini : 0-20 %

Produced mainly by Sq.Cell Ca. of Cx, Vagina & Vulva

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