Serum and peritoneal CA-125 levels as diagnostic test for endometriosis

European Journal of Obstetrics & Gynecology and Reproductive Biology 66 (1996) 41-43

ELSEVIER

Serum and peritoneal CA-l 25 levels as diagnostic test for endometriosis Nicola Colacurci* a, Nicola Fortunate”, Pasquale De Franciscisa, Mario Frattab, Michele Ciofflb, Roberto Zarconea, Antonio Cardonea a2ndDepartment of Gynecology and Obstetrics, Institute of Gynecology and Obstetrics, School of Medicine, Second

Universit,y of Naples,

Naples, Italy bInstitute of General Pathology and Oncology, School of Medicine, Second University of Naples, Naples, Italy

Received 22 September 1995; revision received 13 October 1995; accepted 5 December 1995

Abstract Objective: To evaluate the clinical utility of CA-125 in the diagnosis of endometriosis and to compare the sensitivity of the serum and the peritoneal test as indicator of disease. SW.$J design: Peritoneal fluid was obtained at laparoscopy. The quantitative determination of CA-125 in serum and in peritoneal fluid was performed by IRMA-mat CA-125 ‘two-step method’, a two-site immunoradiometric assay, using 35 and 60 U/ml as cutoff. Setting: Second Department of Gynecology and Obstetrics, Second University of Naples, Italy. Participants: A total of 26 women infertile undergoing diagnostic laparoscopy that exhibited endometriosis in 14 patients, normal pelvis in 12 patients (control group). Interventions: None. Results: CA-125 levels in peritoneal fluid were higher than those found in serum and were significantly elevated (P < 0.05), when compared with the control group, both in women with endometriosis stage I-II and stage III-IV. In serum, CA-125 levels increased only in advanced stage of endometriosis. Conclusions: Levels of CA-125 in peritoneal fluid seem to be a more sensitive indicator of disease than serum levels (0.86 vs. 0.36), especially in early stage endometriosis (0.80 vs. 0.20) which tends to be overlooked by the CA-125 serum test. Keywork

CA-125; Endometriosis; Infertility; Laparoscopy; Peritoneal fluid; Immunoradiometric

1. Introduction CA-125 is a high molecular weight antigenic determinant expressed on the surface of the coelomic epitheliurn, including the epithelium of the endocervix, endometrium, fallopian tube, pelvic peritoneum, and placental tissues. Besides its present in those tissues, CA-125 is well known to be elevated in biological fluids such as human milk, amniotic and peritoneal fluids (PF). The CA-125 antigen is detectable by the murine monoclonal immunoglobulin Gl OC-125 and by the monoclonal antibody M 11. Prior to 1986, the clinical use of this antibody had been limited to the detection and management of ovarian and endometrial advanced cancer; subsequently l Corresponding author, Large Madonna delle Grazie 1, 80138 Naples, Italy; Tel.:+39 81 5665643/5665599/m, Fax:+39 81

459908/664640.

assay

many studies found that serum concentrations of CA125 (I 35 U/ml in healthy blood donors) in women exhibited a variable expression during the normal menstrual cycle, with peak during menses, and in other non-malignant conditions such as endometriosis [l-6]. Recently, several teams have evaluated CA-125 levels also in peritoneal fluid, but they have exhibited conflicting results, probably because of the different assay methods [ 1,7-g]. The aim of the present study is to determinate the clinical utility of CA-125 in the diagnosis of endometriosis, and to compare the sensitivity of the serum and the peritoneal test as indicator of disease. 2. Materials and methods CA-125 serum and peritoneal levels have been evaluated in 14 infertile women undergoing diagnostic laparoscopy that exhibited endometriosis, staged according

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N. Colacurci et al. /European

Joumal of Obstetrics & Gynecology and Reproductive

to the revised American Fertility Society classification (group 1, stage I-II: eight patients; group 2, stage III-IV: six patients). The results were compared with a sample of 12 women suffering from primary infertility who presented at laparoscopy a normal pelvis. Every laparoscopy was performed between the 7th and the 10th day of the cycle. Blood samples were always drawn from the subjects immediately before the induction of general anesthesia. Peritoneal fluid samples were aspirated always at the beginning of the laparoscopy, taking best care to avoid contamination by blood. The quantitative determination of CA-125 in serum and in peritoneal fluid was performed using IRMA-mat CA-125 ‘two-step method’, a two-site immunoradiometric assay (sandwich principle): the monoclonal antibody M 11 is used for the coating of the solid phase (coated tube), the monoclonal antibody OC 125 is used for the tracer. During the first incubation, the CA-125 present in patient samples and standards is bound to the antibody immobilised at the test tube wall. Unbound material is removed by a washing step. During the ensuing second incubation, the tracer antibody reacts with the CA-125 already bound. After removal of excess tracer by a second washing step, the radioactivity remaining at the tube wall is measured in a gamma scintillation counter. The clinical utility of serum and peritoneal CA- 125 in the diagnosis of endometriosis is evaluated by comparing sensitivity; we used 35 U/ml as cutoff for serum measurements [2,10]; for peritoneal test, since we don’t have a standard value as cutoff, the upper limit of normal is defined as 2 SD. above the mean of the control group (1 I]. Sensitivity is defined as the number of patients with all stages of endometriosis who had CA-125 levels > 35 U/ml, divided by the total number of patients with endometriosis [ 121. We couldn’t evaluate the specificity because we omitted from the controls women with gynecologic diseases other than endometriosis. Statistical analysis was carried out using Student’s t-test. Probability values < 0.05 were considered significant. Results are reported as mean f S.D. 3. Results Patients with endometriosis stage I-II (group 1) had Table 1 Serum and peritoneal CA-125 levels

Group 1 (stage I-II) Group 2 (stage III-IV) Controls

Serum CA-125

PF CA-125

17.7 l 15.1 58 f 25.7f 16 z+z4.8

221.4 zt 142.?+ 485 zt 242.3’ 38 f 9.2

Values are means f S.D. lP < 0.05 compared with the control group.

Biology 66 (19%)

41-43

Table 2 Reliability of serum’ and peritonealb CA-125 levels for the diagnosis of endometriosis Serum

Sensitivity

Peritoneal fluid

Total

Stage I-II

Stage III-IV

Total

Stage I-II

Stage III-IV

0.36

0.20

0.75

0.86

0.80

1

‘CA-125 > 35 U/ml. bCA-125 > 60 U/ml.

mean serum CA-125 levels of 17.7 U/ml (range 1.6-43.6; S.D. 15.1), not statistically different from controls (16 U/ml; S.D. 4.8), nevertheless lower than the cutoff value (35 U/ml). Patients with stage III-IV endometriosis (group 2) had significantly higher (58 U/ml; range 34.9-92.4; S.D. 25.7) CA-125 levels compared with the normal pelvis group (P c 0.05) (Table 1). Peritoneal CA-125 levels in the controls appeared higher than serum CA-125 concentrations (38 U/ml; S.D. 9.2), therefore on these values we used 60 U/ml as cutoff for peritoneal measurements. Peritoneal CA-125 levels in patients with all stages of endometriosis (stage I-II 227.4 U/ml; stage III-IV 485 U/ml) were significantly higher than the controls (P < 0.05) (Table 1). The sensitivity is reported in Table 2. 4. DIsel&on Many investigators I6,13-171 have studied the value of CA-125 as a diagnostic test for endometriosis. Serum CA-125 concentrations in the present study are in good agreement to those reported in literature: we found a significantly difference only between patients with endometriosis stage III-IV and the controls (P < O-05), whereas women with early stage endometriosis exhibited low levels which aren’t statistically significant. The sensitivity of CA-125 serum measurement is too low (0.36) to use as a screening or diagnostic test for endometriosis; nevertheless many authors have shown that the test is helpful in monitoring the progress of patients after medical or surgical therapy [4,10,18-201. In peritoneal fluid, a significant difference (P < 0.05) was found between both groups 1 and 2 and the controls. Our results show that CA-125 levels in PF appear to be a more sensitive indicator of disease than serum concentrations (0.86 vs. 0.36), mainly in stages I-II (0.80 vs. 0.20) which tends to be overlooked by the CA125 serum test. Similar results led Barbati et al. [7] to attempt a clinical use of CA-125 in PF aspirated by culdocentesis: the test can be helpful to screen women at risk to undergo laparoscopy. To date, the utility of CA125 in the detection of early stage endometriosis is how-

N. Colacurci et al. /European Journal of Obstetrics & Gynecology and Reproductive Biology 66 (1996) 41-43

ever limited because of its low specificity [7], nevertheless it could be helpful in monitoring the effectiveness of treatment in women with endometriosis stage I-II. Moreover, the low values of peritoneal CA- 125 found in the controls suggest to define an exact cutoff, which must be assessed on a large population and must take the assay and the dilution of the samples into consideration [11,21-231. As a conclusion, further investigations are needed to verify the sensitivity of serum and peritoneal CA-125 as diagnostic test for endometriosis: using cutoff levels lower for serum [lo] and higher for PF, or different assays with high dilutions of the samples [7]. We are trying to use others markers (CA 72.4, IL-6, IL-S) to verify the reliability of a single serum and/or peritoneal drawing for the diagnosis of endometriosis. References

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