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Tumor
Marker: An Overview
By
Brijesh Salwani
Tumor
markers are vital indicators of the status or progression
of a cancer. Consequently, tumor marker assays are prescribed
at different stages of the disease, before therapy,
to obtain a patient reference value, during therapy
to monitor efficacy, and during evolving recurrent disease
to determine appropriate treatment. An ideal tumor maker
(TM) would be a substance produced only by the neoplasic
cells, specific to one type of tumor (no false positives)
and detectable right from the initial stage of the disease
(no false negatives). It would be undetectable in healthy
subjects, and enable the screening and diagnosis of
cancer. The [TM] level would correlate closely with
tumor size, contribute to the initial extension of the
profile and evaluation of therapeutic efficacy, as well
as the early detection of recurrent diseases.
The clinical use of TMs has 3 main indications.
1. SCREENING: The use of TMs for systematic screening
is of no interest. Only targeted screening of thyroid
medullary cancer using CT and hepatocarcinoma using
AFP is justified.
2. DIAGNOSIS: The diagnostic use of TM is rare, but
is limited to the following assays: ßhCG for germinal
tumors, AFP for hepatocarcinomas, CT for thyroid medullary
cancer, PSA for prostate cancer. To improve the diagnostic
performance of PSA, different criteria have been proposed:
* The PSA density (ratio of PSA to gland size), PSA
velocity (annual increaseof PSA), Level of PSA linked
to patient age and free PSA/total PSA ratio.
3 PROGNOSIS: The prognostic value of TMs is generally
linked to the tumor size and often indicates the extent
of disease. The only TMs with an independent prognostic
value for the extent of disease are: CEA in colorectal
cancer,
-
hCG and AFP for germinal tumors, CYFRA 21-1 in non-small
cell pulmonary cancer, LDH in germinal tumors and
lymphoma. Although tumor markers (TM) can be used
in specific cases for cancer screening, diagnosis
and prognosis, the two major uses for these parameters
in routine analyses are therapeutic monitoring of
patient status and early detection of recurrent disease
and metastases.
3
THERAPEUTIC MONITORING
Therapeutic monitoring is evaluated by tracing the evolution
of TM levels measured using the same technique within
the same laboratory. Each patient is considered to be
their own control and any reference to normal values
should be abandoned.
Individual kinetics of the marker level
Integration of clinical and therapeutic data to the
TM individual kinetics graph, as logarithmic coordinates,
enables the different kinetic parameters to be calculated.
To evaluate therapeutic efficacy, the TM half-life (T
1/2) and its minimum level obtained during treatment
(min[TM]) are measured.
Minimum level obtained during therapy min[TM]
The min[TM] is a good indicator of residual disease.
Its value and the time taken to obtain the result depend
on the type of therapy administered and its efficacy.
The persistence of a high min[TM] level reveals the
existence of a remaining secreting tumor. A return to
usual values is not always associated with sterilization
of the tumor.
The value can correspond to the persistence of small
remaining tumors or the disappearance of the only secreting
cell clone. For TMs for which the half-life is short,
the persistence of a detectable level 3 weeks after
complete surgical resection indicates the persistence
of residue, probably due to a tumor.
EARLY
DETECTION OF RECURRENT DISEASE AND METASTASES
A biological recurrent disease is characterized by the
appearance of the evolutive TM profile.
Individual kinetics of the TM level
An exponential increase in TM levels, even within normal
values, indicates renewed evolution. The TM doubling
time can evaluate the evolution increase rate.
Doubling time (dT)
The doubling time is calculated using 3 points, and
reflects the initial increase rate of the recurrent
disease. It also enables the monitoring schedule, therapeutic
strategy, and type of therapy administered to be adapted
early to the agressivity of the recurrentdisease.
When to prescribe TM?
Before therapy: to obtain a reference value. During
therapy: according to a rhythm adapted to the type of
therapy, the half-life and the initial level of TM.
During therapeutic monitoring: with a frequency adapted
to The risk of recurrent disease, the average time lapse
before the onset of recurrent disease, and the therapeutic
alternatives available. During evolving recurrent disease:
according to a rhythm adapted to the doubling time of
the TM.
Analysis of discrepancies
Clinical: Modification of the filtration functions of
TM (hepatic or renal insufficiency),
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Tumor heterogeneity, Massive tumor cytolysis or regeneration
of hepatocytes,
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Inadequate evaluation (even dissociation) of the clinical
response, Analytical:
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Problem of reagent standardization, Variable sensitivity
of reagents to the hook effect or interfering substances,
Problem of international standardization, Molecular
heterogeneity of TM, Presence of HAMA*.
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Mouse anti-human immunoglobulin Antibodies Can TMs
be detected elsewhere than in blood? After surgery,
the expression of TM in tumor cells can be detected
in tissue using the immunohistochemical technique.
TMs can also be assayed in biological fluids such
as:
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Urine (catecholamines and NSE in neuroendocrine tumors),
Pleural fluid (hyaluronic acid in mesotheliomes),
Ascite fluid (CA 19-9 and CEA in peritoneal carcinosis),
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CSF (NSE in organic neurological pathologies) What
is the interest of the enzymatic assays in cancerology?
They can usefully complete the information linked to
TMs. If the increase in some enzymatic activities (i.e.
ALP, 5’Nu, ??GT, LDH) indicates a non-specific
response of the liver parenchyma to the invading tumor,
other hyperactivities are a more specific result of
the existence of a tumor: BAP (primary or metastatic
bone tumor), PAP (prostatic tumor), lysozyme (myeloproliferative
syndromes) etc.
ALWAYS REMEMBER
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A normal TM level does not exclude cancer
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A high TM level does not always indicate cancer.
ESSENTIAL
DO’S...
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Assay the TM level before administering therapy
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Interpret the TM level taking into account the clinical
and radiological context. Control all positive results
indicating the need for therapeutic decision-making
using a new sample.
-
Monitor patients using the same technique in the same
laboratory.
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Store sera in a serum bank.
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Examine the background history when changing assay
technique. 7. Integrate the individual evolution kinetics
of the TM in the patient report.
ESSENTIAL DON’TS
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Assay a marker when no therapy is available.
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Monitor the tumor site using several TMs, which are
not really complementary.
The Vidas tumpur marker guarantees accurate and reliable
TM measurements in clinical samples.
(The author is product manager, Vidas
Tumor Markers and can be contacted at mktg.bmxindia@satyamlanmail.com)
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