The presence of multiple epitopes on tumor antigen together with non- specificity of tumor markers necessitates the use of Monoclonal antibodies (MAb) for detection. Both

 

Features of Tumor Marker

¾ Should be identified by biochemical, immunological or

molecular biological methods

¾ Measured easily, reliably and cost effectively using an

assay with high analytical sensitivity and specificity.

¾ Quantitative level of tumor marker reflects tumor

burden with diagnostic sensitivity (few false negatives)

and specificity (few false positives).

¾ Test result influence patient care and outcome.

What are the Clinical Applications of Tumor Markers?

Monitoring Treatment

One of the most important applications of tumor markers

lies in supervising the course of the disease, especially

during treatment. Most other clinical procedures lack

the sensitivity and convenience for such frequent

examinations. The levels of the tumor marker will inform

whether the patient is experiencing remission or relapse

and will also determine the effectiveness of the treatment.

During the course of chemotherapy, the level of the

tumor marker may indicate when there is a need for a

redesign of medication, because many a times tumor cells

develop drug resistance.

Detection of Recurrence

Monitoring tumor marker for the detection of recurrence

following surgical removal of the tumor is an important

clinical application. It is desirable to monitor the patient

using highly sensitive onco Immunoassays tests in order

to detect recurrence as early as possible.

While monitoring for recurrence, the slope (the rate

of increase of tumor marker concentrations with time)

680 Concise Book of Medical Laboratory Technology: Methods and Interpretations of tumor marker is important. The slope is a major factor

guiding therapeutic strategies.

Prognosis

In patients with cancer, tumor markers help in assessing

the tumor aggressiveness, which in turn determines how a

patient should be treated. Because serum concentration of

tumor marker increases with tumor progression and usually

reaches the highest levels when tumor becomes metastasized,

the serum level of tumor markers at diagnosis are likely to

reflect the aggressiveness of the tumor and help predict the

outcome for the patient. A low serum level indicates that the

tumor is at an early stage or still organ confined.

Diagnosis

Diagnosis is a procedure that determines definitively

whether a person has cancer. The frequency of raised levels

of an isolated tumor marker in nonmalignant diseases

and the overlap between normal concentrations and the

concentrations of tumor markers in patients with proven

cancer discourages their isolated usage for diagnosis.

The use of multiple markers simultaneously to observe

specific patterns of tumor marker is widely accepted as a

reliable tool for diagnosis.

Diagnostically Important Tumor Markers

Tumor marker Condition

PSA Prostate cancer

CEA Colorectal cancer, breast cancer

AFP Testicular cancer, liver cell cancer

HCG Germ cell tumors, trophoblast cancer

CA 125 Ovarian cancer

CA 15-3 Breast cancer

CA 19-9 Pancreatic cancer, biliary tract cancer

What are the Factors that Affect Tumor Marker Diagnosis?

Specificity

Most markers are not specific for a tumor.

Single tumor (breast cancer) Multiple marker (CA 15-3, CEA)

Single marker (CA 125) Multiple tumors (ovarian, lung,

uterine caner)

Multiple Epitopes: Epitopes are Antibody Binding

Sites on the Antigen

Tumor cells have many tumor antigens. Each antigen has

multiple epitopes. Use of Polyclonal antibodies as capture

and tracer may lead to non-specific binding (Fig. 22.28).

Hook Effect

By definition, “a falsely low value produced by the

immunoassay when the actual concentration of the sample

is highly elevated is termed as Hook effect”. It occurs most

commonly in sandwich type immunoassay when only one

incubation is performed.

Serum Half-life of Tumor Marker

It refers to the time for the serum concentration of the

tumor marker to drop to half of its original concentration.

Use of Polyclonal Antibodies

Polyclonal antibodies have poor reproducibility and

can cross react. Also the lot-to-lot variation is more in

polyclonal antibodies.

Sensitivity

Many immunoassay techniques suffer from poor

sensitivity. Sensitivity of an immunoassay is very

important in case of tumor recurrence after surgery,

where the levels of the tumor marker should be very

low. Increase in values after surgery indicates tumor

recurrence. Also detection of very low values may have a

prognostic effect.

FIG. 22.28: Schematic representation of tumor cell

Serology/Immunology 681

New Concepts in Tumor Marker Diagnosis

Multiple Marker Testing (MMT)

Due to lack of specificity, use of more than one marker

increases the chances of detecting tumors. Using multiple

tumor markers increases the possibility of detecting an

elevation of markers in an increasing number of benign

and nonmalignant diseases.

Use of Monoclonal Antibodies

The presence of multiple epitopes on tumor antigen

together with non- specificity of tumor markers necessitates

the use of Monoclonal antibodies (MAb) for detection. Both

the tracer and capture antibodies should be monoclonal in

nature. MAb are very expensive and only few have them.

MAb have the following advantages:

¾ High specificity

¾ High reproducibility

¾ No lot-to-lot variation

¾ No cross reaction

¾ Ideal for tumor marker immunoassays.