FERTILITY AND STERILITY Vol. 45, No.

6, June 1986
Copyright © 1986 The American Fertility Society Printed in U.S.A.

CA-125 levels in endometriosis

Phillip E. Patton, M.D.

Charles S. Field, M.D. *
Roger W. Harms, M.D.
Carolyn B. Coulam, M.D.t

Department of Obstetrics and Gynecology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota

C;A-125 is a cellular antigen detected in many patients with ovarian cancer, but it
has also been detected in patients with endometriosis. Preoperative CA -125 levels were
drawn from 113 patients before they underwent laparoscopy. Patients were categorized
into diagnostic groups on the basis of pathologic findings. CA -125 levels in patients
with evidence of intraabdominal adhesions were not statistically different from those
in patients with normal pelvic anatomy. However, patients with advanced
endometriosis had significantly elevated levels of CA-125 when compared with
patients with normal pelvic anatomy (P < 0.05). The clinical and immunologic
implications of elevated CA-125 levels in patients with advanced endometriosis are
discussed. Fertil Steril 45:770, 1986

The monoclonal antibody OC-125, obtained by
hybridization of a mouse myeloma cell line with
spleen cells from mice immunized with the anti-
genic determinant CA-125, has been found in the
majority of epithelial carcinomas as well as in
Mullerian duct derivatives, fetal tissues, endome-
trium, and endocervix. 1-4
Previously, it has been reported 5 that CA-125
levels may also be elevated in patients with en-
dometriosis. Currently, a reliable noninvasive
screening test to detect endometriosis does not
exist. The purpose of this study is to determine
the efficacy ofCA-125 measurements as a screen-
ing procedure for endometriosis. The clinical and
Received November 18, 1985; revised and accepted Febru-
ary 27, 1986.
*Reprint requests: Charles S. Field, M.D.; Department of
Obstetrics and Gynecology, Mayo Clinic, 200 First Street SW,
Rochester, Minnesota 55905.
tPresent address: Division of Reproductive Biology, Uni-
versity of Pittsburgh, Magee Women's Hospital, Pittsburgh,
Pennsylvania.
immunologic implications of the results are dis-
cussed.
MATERIALS AND METHODS
A total of 113 women with no systemic illnesses
who underwent laparoscopy between January
1985 and June 1985 were enrolled in the study.
Their ages ranged from 16 to 48 years, with a
mean age of 30.5 years. At the time of laparos-
copy, the presence of endometriosis, pelvic adhe-
sions, or other pelvic pathology was prospectively
recorded. The stage of endometriosis was cate-
gorized according to The American Fertility So-
ciety Classification. 6 Endometriosis was diag-
nosed by visual findings at laparoscopy, and in
73% of patients, a biopsy confirmed the diagnosis.
Two patients with suspected endometriosis had
only hemosiderin on biopsy and were not included
in the analysis of the endometriosis patients.
Indications for laparoscopy included infertility
(n = 50, 44%), elective sterilization (n = 49,
43%), pelvic pain (n = 11, 10%), and premature

770 Patton et al. CA-125 levels in endometriosis Fertility and Sterility

Table 1. Diagnostic Groups and CA-125 Levels
Group n Mean CA-125
No pathologic findings
Pelvic adhesions
Endometriosis
Other
Total 113
Endometriosis stage lIII
Endometriosis stage III/IV
aSignificantly different from group I (P < 0.05).
ovarian failure (n = 3, 2.6%). After laparoscopy,
the patients were divided into the following
groups on the basis of operative findings: (1) no
pathologic abnormalities; (2) endometriosis; (3)
pelvic adhesions; and (4) other, e.g., leiomyoma
and premature ovarian failure.
Serum samples were obtained from all patients
immediately before induction of anesthesia.
CA-125 levels were measured by radioimmunoas-
say (RIA) as previously described. 4 The distribu-
tion of the data was normalized by log transfor-
mation of the data followed by analysis by the
t-test.
RESULTS
Of the 113 patients who underwent laparos-
copy, 45 (40%) had no pelvic abnormalities noted,
37 (33%) had endometriosis, 26 (23%) had pelvic
adhesions, 2 (1.6%) had leiomyomas, and 3 pa-
tients (2.6%) had premature ovarian failure. Be-
cause the number of patients in each stage of
endometriosis was small, patients with stage I
and stage II were combined to constitute one
group (stage IIII), and stage III and stage IV were
combined to constitute a second group (stage IIII
IV). CA-125 levels in each group are presented in
Table 1.
CA-125 levels in patients with stage IIIIIV
were significantly elevated when compared with
the normal pelvic group (P < 0.05). No other sig-
nificant differences were noted among the groups
tested. Three patients in the normal pelvis group
and two patients in the pelvic adhesions group
had CA-125 levels> 35 VlmI. Five patients in the
endometriosis group (two in stage IIII and three
in stage IIIIIV) had levels> 35V1mI.
The sensitivity and specificity of CA-125 at a
level of 35 Vlml were tested in all patients with
Vol. 45, No.6, June 1986
Range CA-125 Standard deviation
Ulml Ulml
45 17.88 8.0-47.9 9.25
26 18.59 6.0 - 65.0 11.60
37 23.45 7.7 -105.6 16.87
5 16.09 10.7 - 23.0 4.88
22 19.27 8.2 - 42.6 9.23
15 28.51a 7.7 - 105.6 23.57
endometriosis and patients with stage IIIIIV dis-
ease. Sensitivity was defined as the ratio of pa-
tients with endometriosis and CA-125 levels > 35
Vlml to all patients who had documented endo-
metriosis. Specificity was defined as the ratio of
patients without endometriosis with CA-125 lev-
els < 35 Vlml to all patients without documented
endometriosis. In all patients with endometriosis,
sensitivity and specificity were 0.14 and 0.93, re-
spectively. In patients with stage III/IV disease,
sensitivity and specificity were 0.18 and 0.93,
respectively.
DISCUSSION
The antigenic determinant CA-125 has been
detected in various coelomic epithelial deriv-
atives by the use of RIA. It has been used pri-
marily in the detection and investigation of pa-
tients with ovarian cancer, but elevated serum
levels have been detected in patients with car-
cinoma of the endometrium, fallopian tube, and
breast, as well as pregnancy and benign liver dis-
ease. 1 -3 , 7, 8 Recently, elevated levels have been
reported in patients with endometriosis. 5 Because
a noninvasive screening test for endometriosis
does not exist, the diagnostic use of CA-125 was
evaluated in patients undergoing laparoscopy for
various reasons.
The monoclonal antibody (OC-125) is a murine
IgG l that recognizes the antigenic determinant
referred to as CA-125. CA-125 is a glycoprotein
with a molecular weight of approximately
200,000 daltons, but further characterization of
the antigen is lacking. Immunoperoxidase stain-
ing can identify the CA-125 antigen in membrane
fractions of ovarian carcinoma lines with little
staining noted in normal endometrium.g,lo In
endometriosis, it is not known whether the de-
Patton et al. CA-125 levels in endometriosis 771
tected antigen arises from stroma, epithelium, or
peritoneum.
Only 1% of normal patients who do not have
ovarian carcinoma have levels> 35U/ml. 4 The
use of this study population as a control may be
biased because it included patients with a wide
variety of nonmalignant diseases, including en-
docrine, cardiorespiratory, renal, collagen-vascu-
lar, and gastrointestinal disorders. Unrecognized
gynecologic disease may have been present in
these patients as well.
In the present study, healthy female patients
were evaluated historically and by laparoscopy,
and a control group was defined by negative
pathologic findings at laparoscopy. It is also pos-
sible that the control group had unrecognized
gynecologic or medical disease that may have af-
fected CA-.l25 levels. In fact, three patients in the
normal pelvis group had levels> 35 Vlml without
an identifiable cause.
Patients with advanced endometriosis (stage
III/IV) had significantly elevated levels ofCA-125
when compared with a group of patients with
normal pelvic anatomy. Patients with less signifi-
cant endometriosis or adhesions did not have lev-
els which differed from the control population.
Unfortunately, despite the elevated levels in pa-
tients with advanced endometriosis, the low sen-
sitivity of CA-125 in endometriosis precludes its
use as a screening procedure. Although the mean
values may show a significant difference, the data
indicate that there is considerable overlap of
CA-125 values in the various study groups.
Nevertheless, the elevated levels of CA-125 in
patients with moderate and severe endometriosis
may still have important clinical and immuno-
logic promise. Previous investigators4 , 11, 12 have
shown that antigenic proteins can be detected in
rapidly proliferating tissues of both benign and
malignant tissues. It is possible that antigenic
proteins are released in endometriosis, because
patients with advanced endometriosis have sig-
nificantly increased levels of CA-125.
The proteins detected by OC-125 in patients
with endometriosis and ovarian cancer may be
identical. A secreted protein in endometriosis
may not be released until there is advanced dis-
ease, or may be released in early disease but may
not reach detectable concentrations until there is
advanced disease. In contrast, the protein de-
tected by the monoclonal antibody in patients
with endometriosis and ovarian cancer may be
dissimilar. The monoclonal antibody may recog-
772 Patton et al. CA-125 levels in endometriosis
nize a similar or identical epitope in structurally
different proteins. The affinity of OC-125 for an
endometriosis protein may be so low that the pro-
tein is only detected at high concentrations such
as in states of advanced endometriosis. A protein
could be secreted at early stages of endometriosis
but is not detected by OC-125 because of its low
affinity and low concentration.
If an antigenic protein unique to endometriosis
can be characterized, isolated, and purified, then
a noninvasive screening procedure could be de-
veloped. The analysis of proteins with the anti-
genic determinant CA-125 in patients with endo-
metriosis and other disorders may be useful. Mo-
lecular or chemical characterization may be able
to determine whether the proteins are identical,
dissimilar, and unique.
Acknowledgment. We would like to thank R.E. Ritts, M.D.,
for performance of the CA-125 assays.
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