domain is characterized by polymorphism with respect to the number of a 20 amino acid tandem repeat (VNTR polymorphism). The MUC-1 breast cancer mucin < (CA15-

 

¾ Combined with total PSA, DRE and biopsy findings,

helps to predict the postoperative pathological stage

and grade, and may assist the patient and physician in

making more informed treatment decisions.

¾ Can help differentiate CaP (carcinoma of prostate)

from BPH and reduce unnecessary biopsies.

Cancer Antigens

These are epitopes recognized on the surface of high

molecular weight glycoproteins on the epithelial cells lining

respiratory, gastrointestinal and many other secretory

tissues.

CA 125

¾ An epitope associated with a high molecular weight

glycoprotein

¾ Originally identified by MAb OC 125

¾ A marker for ovarian cancer

¾ Elevated in ovarian, lung, pancreatic and uterine cancer

¾ Used in differential diagnosis between ovarian cancer

and benign disease.

CA 15-3

¾ An epitope on mucin type glycoprotein antigen

¾ The antigen is present in normal and malignant epithelial

cells of certain organs — breast, lung, ovary, etc.

¾ Elevated levels are observed in patients with metastatic

breast cancer

Also elevated in chronic hepatitis, liver cirrhosis,

tuberculosis and SLE.

CA 242

¾ An epitope on sialylated carbohydrate antigen

¾ Present on mucinous type of glycoprotein

¾ Elevated in patients with gastrointestinal cancer

¾ Discrimination between benign and malignant

pancreatic disease

¾ Complement to CEA in colorectal cancer.

hCG

A glycoprotein secreted by the syncytiotrophoblasts of

placenta contains α and β subunits.

Forms of hCG

In maternal serum found in many forms

¾ Intact hCG

¾ Free subunits (free β)

¾ Partially degraded form.

Objectives of hCG Estimation

¾ Pregnancy test

¾ Ectopic pregnancies

¾ Molar pregnancies

¾ Diagnosing trophoblastic disorders

¾ Germ cell neoplasms

¾ Testicular carcinoma.

Strategies of hCG Assays

The hCG assays employ different strategies for estimating

hCG from urine (qualitative) and serum (quantitative).

The serum hCG assay measures the intact (whole)

molecule when an antibody or the α-subunit and an

antibody for β-subunit are used in the immunometric

format. This type of assay does not measure free α/ β–

subunit because free subunits cannot form sandwich with

both antibodies. The total β-hCG assay measures both the

intact hCG and free β-subunits. As a tumor marker, a total

β-hCG assay may be preferred.

Before Selecting an hCG Assay

It is of utmost importance to check:

¾ Calibrators—calibrated against 3rd IS (WHO)

¾ Calibrator matrix—human serum matrix

¾ Cross reactivity with LH—very little or no cross

reactivity.

Serology/Immunology 683

TUMOR MARKERS STANDARD

METHODOLOGIES AVAILABLE ON

ELISA AND CLIA, AS ON RIA TOO.

Alpha-Fetoprotein (AFP) ELISA

Summary and Explanation of the Test

Alpha-Fetoprotein (AFP) is a glycoprotein with a

molecular weight of 70 kDA. AFP is normally produced

during fetal development by the hepatocytes, yolk sac

and to a lesser extent by the gastrointestinal tract. Serum

concentrations reach a peak level of up to 10 mg/mL at

12 weeks of gestation. This peak level gradually decreases

to less than 25 ng/mL after 1 year of postpartum. Thereafter,

the levels reduce further to less than 10 ng/mL.

Elevated levels of AFP are found in patients with primary

heptatoma and yolk sac-derived germ tumors. AFP is the

most useful marker for the diagnosis and management of

hepatocellular carcinoma.

AFP is also elevated in pregnant women. Presence of

abnormally high AFP concentrations in pregnant women

provides a risk marker for Down syndrome.

Interpretation

AFP has a low clinical sensitivity and specificity as a tumor

marker. Clinically an elevated AFP value alone is not of

diagnostic value as a test for cancer and should only be

used in conjunction with other clinical manifestations

(observations) and diagnostic parameters. AFP levels are

known to be elevated in a number of benign diseases and

conditions including pregnancy and non-malignant liver

diseases such as hepatitis and cirrhosis.

Expected Ranges of Values

Approximately 97 to 98% of the normal healthy population

has AFP levels less than 8.5 ng/mL. In high risk patients, AFP

values between 100 and 350 ng/mL suggest hepatocellular

carcinoma. Concentrations over 350 ng/mL usually are

indication of the disease.

Expected values for the AFP ELISA Test System male

and female < 8.5 ng/mL (97–98%).

It is important to keep in mind that establishment of

a range of values which can be expected to be found by

a given method for a population of “normal’-persons is

dependent upon a multiplicity of factors the specificity

of the method, the population tested and the precision of

the method in the hands of the analyst. For these reasons

each laboratory should depend upon the range of expected

values established by the Manufacturer only until an inhouse range can be determined by the analysts using the

method with a population indigeneous to the area in which

the laboratory is located.

CA 15-3 (CARCINOGENIC ANTIGEN 15-3)

(Courtesy: Lilac Medicare)

Summary and Explanation of the Assay

The MUC-1 antigen is a membrane-anchored mucin-type

glycoprotein present in malignant and normal epithelial

cells of certain organs, e.g. breast, lung, ovary and

pancreas. The apo-protein of the MUC-1 mucin contains

a transmembrane domain, a cytoplasmic domain, and an

extracellular carbohydrate rich domain. The extracellular

domain is characterized by polymorphism with respect

to the number of a 20 amino acid tandem repeat (VNTR

polymorphism). The MUC-1 breast cancer mucin < (CA15-

3 antigen) is secreted from tumor cells and can be used as

a serological marker of breast cancer.

The expiry date of the complete kit is stated on the label

on the outside of the kit box.

Do not use the kit components beyond the expiry date.

Do not mix reagents from different lots of kits.

Store the kit at + 2–8°C.