What
Is CA 125?
Cancer Antigen 125 (CA 125) is an antigenic determinant on a glycoprotein
recognized by a monoclonal antibody. It is expressed in the amnion
and its derivatives of fetal coelemic epithelia. The antigen is also
found in several adult tissues such as the epithelium of the fallopian
tubes, the endometrium, the endocervix, the pleura, and the peritoneum.
Thus, the normal tissues of the body, namely the endometrium, produces
a basal level of CA 125 which can contribute significantly to the
level of circulatory or serum CA 125.
When Is CA 125 Elevated?
While a basal level of circulating CA 125 may be expected, there exist
many conditions in which the level of the antigen may be elevated.
These conditions may be better understood by classifying them into
non-gynecological and gynecological processes. Various studies have
documented an elevation in CA 125 in a few non-gynecological conditions,
including cirrhosis of the liver and tuberculosis. Cancers of the
pancreas, breast, colon, and lung have also been found to express
higher levels of CA 125. Studies are currently underway to determine
the efficacy of using CA 125 in the diagnosis and management of various
types of cancers. Meanwhile, gynecological processes such as pelvic
inflammatory disease, endometriosis, and menstruation have been implicated
in raising the serum level of CA 125. Other conditions such as benign
ovarian cysts, tubo-ovarian abscess, hyperstimulation syndrome, ectopic
pregnancy, and fibroids also have been correlated with elevated levels
of CA 125. Finally, when compared with the normal, non-pregnant state,
the antigen levels in pregnant women have been observed to be significantly
higher during the first trimester, but not during the second and third
trimesters. While these non-gynecological and gynecological conditions
have been associated with increased levels of CA 125, the highest
serum levels of the antigen are found in ovarian cancer patients.
How Can CA 125 Be Used In Patients With Ovarian
Cancer?
CA 125 estimation is of clinical value in the pre-operative diagnosis
and monitoring of ovarian malignancies. Available data suggests that
CA 125 is elevated in the majority of epithelial ovarian malignancies
prior to clinical presentation. Large trials of screening for ovarian
cancer indicate that using a CA 125 cutoff value of 30 U/ml has good
sensitivity, but inadequate specificity for detecting pre-clinical
disease. The sensitivity of CA 125 is related to stage (40-95 percent)
and histologic type (lower levels in mucinous adenocarcinoma). Use
of transvaginal ultrasonography as a second-line test in women with
elevated CA 125 levels improves specificity to acceptable levels,
as does use of a mathematical algorithm which analyses rates of change
of CA 125. The best-established application of the CA 125 assay is
in monitoring ovarian cancer. Doubling or halving of CA 125 serum
values correlated with tumor progression or regression, respectively.
The rate of decline in CA 125 during primary chemotherapy has been
an important independent prognostic factor in several multivariate
analyses. A deviation from the ideal CA 125-regression curve predicts
poor outcome within three months of treatment. Persistent elevation
of CA 125 at the time of a second look surgical surveillance procedure
predicts residual disease with greater than 95 percent specificity.
Rising CA 125 values have preceded clinical detection of recurrent
disease by at least three months in most, but not all studies. Given
the modest activity of salvage chemotherapy, this information is not
yet impacted on survival. Rising CA 125 during subsequent chemotherapy
has been associated with progressive disease in more than 90 percent
of cases.
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