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Tumor marker CA 125 level and ovarian volume at different cycle day periods and in postmenopause
Int. J. GynecolObstet.,
1990,33: 149-152 International Federation of Gynecology and Obstetrics
149
Tumor marker CA 125 level and ovarian volume at different cycle day periods and in postmenopause S. Granberga, M.Wikland” and L.-G. Fribergb aDepartment of Obstetrics and Gynecology, bDepartment of Oncology, University of Giiteborg, Sahlgrenska sjukhuset, S-41345 Giiteborg (Sweden)
(Received March 23rd, 1989) (Revised and accepted July 26th, 1989)
Abstract The value of using CA 125 for screening of ovarian carcinoma is still under debate. It is important to be aware of possible physiological variation in serum levels of this antigen. This study aimed at finding out whether there were any differences in CA 125 levels in serum at different cycle day periods of fertile women and postmenopausal women. In IO6 women, CA 125 and ovarian volume were measured at different cycle day periods and in postmenopausal women. The highest levels were found in cycle day (CD) l-9, i.e. 22 units/ml and the lowest in postmenopausal women i.e. 6.7 units/ml. No correlation could be found between the CA 12.5 levels and ovarian volume as measured by vaginal sonography. Keywords: CA 125; Ovarian volume; Ultrasound. Introduction Ovarian cancer in women is the most common cause of death from gynecological malignancies. Early diagnosis of ovarian cancer has not improved despite the development of such technical tools as computer tomography (CT), ultrasound and magnetic resonance 0020-7292/90/$03.50
0 1990 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
(MR) [6, lo]. Today about 60% of ovarian cancers are discovered in stages III and IV, a figure that has not changed in the last 20 years [5,10,13]. Various antigens for epithelial tumors have been developed for use in the diagnosis of ovarian cancer and as an early indicator of recurrence of the cancer. One such is CA 125. It is a membrane antigen recognized by monoclonal antibody which was raised using an ovarian cancer cell line as an immunogen. It has been shown to be elevated in the serum of patients with serous epithelial ovarian carcinoma [1,2,7,17]. Bast and coworkers [ 1,2] found that 82% of women with epithelial ovarian carcinomas had increased CA 125 levels. On the other hand, 6% of patients with non-malignant diseases and 1% of healthy women also had elevated CA 125 values [ 1,2,7,17]. Pittaway and co-workers [lg] found differences in CA 125 levels with regard to the time before and after menstruation. This study was aimed at finding out whether there were any differences in CA 125 levels in serum at different cycle day periods of fertile women and postmenopausal women. These levels were then correlated to the ovarian volume. Materials and methods The study included 106 women between 22 Clinical and Clinical Research
150
Granberg et al.
and 76 years of age, who were close relatives of women who had or had had ovarian cancer. Seventy-one women were still menstruating and had proven fertility and 35 women were post-menopausal. None of the women had any history of gynecological disease up to 1 month prior to the time when blood samples were taken and when the ultrasound was performed. Two of the post-menopausal women had mammarian cancer 8 years before the blood sample for CA 125 determination was taken. These women were excluded from the statistical analysis. Blood samples were taken by puncturing of a peripheral vein by use of a vacutainer (Becton, Dickinson Vacuteiner System, France). A radioimmunoassay technique for the monoclonal antibody tumor marker CA 125 was used and has been described elsewhere (ELSA-CA 125 International CIS , France) [ 1,171. Ovarian volume was measured by use of sonography as previously described by Goswamy [lo] and by our group [11,12]. The transabdominal scans were performed using a transabdominal mechanical sector transducer of 3.5 MHz (Diasonic DRFlOO, Mil-pitas CA, USA). The transabdominal scans were performed using the full urinary bladder technique. The endovaginal scans were performed using an endovaginal transducer (Briiel & Kjaer, Naerum, Denmark). This mechanical sector transducer has a 112O sector and 7.5 MHz crystals. The focal length is 6 cm. The women were divided into two groups, menstruating and post-menopausal. The menstruating women were further divided into cycle day periods depending on the day in the cycle the blood sample was taken. The men-
Table I.
strual cycle length for the last 6 months was registerd. The mean was 28 days and the range 26-33 days. The menstrual cycles were grouped into the following periods CD l-9, lo-16 and 17-28. Statistics Mean f SD were calculated for each cycle day periods with regard to CA 125 serum levels and ovarian volume. Linear regression was used for the correlation calculations. For statistical comparison between groups Student’s t-test was used. Results Seventy-one women (68%) had CA 125 values less than 6.5 units/ml and ten women (10%) had values greater than 25 units/ml (Table I). The mean value for menstruating women was 13.6 f 8 units/ml and for postmenopausal women 6.7 f 1 units/ml. The two women with earlier known but treated mammarian cancer had values greater than 35 units/ml. Both these women had normal sized ovaries. CA 125 values during CD l-9 were statistically significantly higher as compared to CD lo-16 and CD 17-28 (P < 0.05). The mean values obtained during CD l-9 and CD lo16 were also significantly higher as compared to postmenopausal values (P < 0.05) (Table II). The mean values of CA 125 serum levels and ovarian volume at different cycle day periods and postmenopause are shown in Table II. No correlation was found between
Number of women at a given cycle day period (CD) and in postmenopause related to level of CA 125.
CA 125 (units/ml)
CD 1-9
CD lo-16
CD 17-28
Postmenopause
Total
< 6.5 6.6-25 >25
2 9 6
20 11 2
17 4 -
32 1 2=
71 25 8
“These two women were excluded from statistical evaluation, see text. Int J Gynecol Obstet 33
CA 125 levels and ovarian volume Table II.
CA 125 serum levels and ovarian
volume at different
Cycle day period
No. of women
Ovarian
l-9 lo-16 17-28 Postmenopause
17 33 21 33(+2)b
3.1 5.8 3.0 1.4
a Mean and SD. bThese two women were excluded
cycle day period and in menopause.
volume”
(cm))
from statistical
2 f k k
2.2 2.9 2.1 1.0
evaluation,
151
CA 125” (units/ml) 22.0 10.2 8.5 6.7
r 12.6 + 6.2 f 5.2 k 1.0
see text.
the CA 125 serum levels and ovarian volume at the different cycle day periods as well as between these parameters in the postmenopause. No postmenopausal woman had CA 125 values greater than 25 units/ml. In the group of menstruating women, eight had CA 125 serum levels above 25 units/ml (see Table I). Dikussion Measurement of CA 125 in blood is a method that has been claimed to be a valuable tool for early diagnosis of non-mutinous epithelial ovarian tumors. However, the value of the method for screening of ovarian carcinoma is still under debate. When using CA 125, it is important to be aware of possible physiological variation in serum levels of this antigen. It is known that CA 125 levels increase during menstruation [18] and in women with endometriosis [3,8,19]. Since the knowledge about CA 125 serum levels in different periods of the menstrual cycle of proven fertile women is very meager, this study was undertaken. Since it is known that there is a correlation between the ovarian volume and the steroid production of the ovary in different cycle day periods it would be of interest to see if such a correlation also could be found in the CA 125 levels. This would then indicate a relation between the steroid production of the ovary and CA 125 production or release. Such a relation has in fact been suggested by the in vitro studies by Bischef and co-workers [4]. Our results showed a maximal CA 125 level
in cycle day period l-9 (22.0 units/ml), whereafter there was a decrease to 10.2 units/ mlinCD10-l6andto8.5units/mlinCD17 -28. The maximal volume of the ovaries was found in the period CD lo-16 which of course is expected due to follicular development. However, there was no correlation between the size of the ovary and the CA 125 serum levels. It could be argued that the increase of estradiol and progesterone in some way influence the production or release of CA 125 since the levels reach maximal values at that time of the cycle when the production of these steroids are at their lowest. It has earlier been shown that CA 125 can be detected in adult tissues, in the fallopian tubes, endometrium and endocervix [ 16,201. The higher CA 125 levels during CD l-9 could thus also be explained by a leakage of CA 125 from the endometrium, as in women with endometriosis [3,8], to the peripheral circulation during the early follicular period of the cycle. Whether this is due to change in the synthesis or a change in the tissue barrier is not known. Due to the fact that laparoscopy was not performed in the women in this study, endometriosis cannot be excluded to be responsible for the higher values found in CD l-9. Our results are comparable with those found by Zurawski and co-workers [20]. In a non-hospitalized population, they found a mean CA 125 level in menstruating women between 14.3 units/ml and 28.2 units/ml, and in postmenopausal women between 10.6 units/ml and 16.3 units/ml. When using CA 125 for detection of Clinical and Clinical Research
152
Granberg et al.
ovarian cancer in menstruating women, attention should be paid to the fact that the serum levels may vary depending not only on pathology in the ovaries but also to physiology of the menstrual cycle. If the blood sample is taken during the early follicular period and a high value is obtained, ultrasound examination of the ovaries could be of value [9,11,14]. Furthermore, if a value of 20 or more units/ ml is found in postmenopausal women, ultrasound may be of importance in excluding an ovarian tumor. Jacobs and co-workers [ 151 found that if ultrasound examination of the ovaries was added to CA 125 measurements -in serum of postmenopausal women, the specificity of the examination increased to nearly 100% when screening for ovarian cancer [ 151. Ultrasound in combination with CA 125 measurement could thus be important when dealing with women at risk for ovarian cancer.
6
7
8
9
10 11
12
13 14
Acknowledgments We are grateful to The King Gustav V Jubilee Cancer Research Foundation in Gothenburg, Goteborg Medical Society and Brtiel and Kjaer, Naerum, Denmark for supporting this study. References Bast RC, Klug TL, Schaetzl E et al: Monitoring human ovarian carcinoma with combination of CA 125, CA 199, and carcinoembryonic antigen. Am J Obstet Gynecol 149: 553,1984. Bast RC, Klug TL, St John E et al: A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med 309: 883,1983. Barbieri RL, Niloff JM, Bast RC et al: Elevated serum concentrations of CA 125 in patients with advanced endometriosis. Fertil Steril45: 630, 1986. Bischof P, Tseng L, Briosch PA, Herrmann WL: Cancer antigen 125 is produced by human endometrial stroma cells. Hum Reprod 1: 423, 1986. Cancer incidence in Sweden 1983. National Board of Health and Wellfare. The Cancer Registery, 1987.
Int J Gynecol Obstet 33
15 16
17
18 19
20
Dembo AJ, Bush R, Beale F: The Princess Margaret Hospital study of ovarian cancer stage I, 11 and asymtomatic III. Cancer Treat Rep 63: 249, 1979. Einhorn N, Bast RC, Knapp RC et al: Preoperative evaluation of serum CA 125 levels in patients with primary epithelial ovarian cancer. Obstet Gynecol67: 414, 1986. Fedele L, Vercellini P, Arcaini L et al: CA 125 in serum, peritoneal fluid, active lesions, and endometrium of patients with endometriosis. Am J Obstet Gynecol 158: 166, 1988. Finkler NJ, Benacerraf B, Lavin PT et al: Comparison of serum CA 125, clinical impression, and ultrasound in the preoperative evaluation of ovarian masses. Obstet Gyneco1 72: 659, 1988. Goswamy RH, Cambell S, Whithead MJ: Screening for ovarian cancer. Clin Obstet Gynecol 10: 1, 1983. ‘Granberg S, Wikland M: A comparison between ultrasound and gynaecologic examination for detection of enlarged ovaries in a group of women at risk for ovarian carcinoma. J Ultrasound Med 7: 59,1988. Granberg S, Wikland M: Comparison between endovaginal and transabdominal transducer for measuring ovarian volume. J Ultrasound Med 6: 649, 1987. Incidence of Cancer in Norway 1985. The Cancer Registery of Norway, Oslo, 1987. Jacobs I, Bridges J, Reynolds C et al: Multimodal approach to screening for ovarian cancer. Lancet I: 268, 1988. Jacobs I, Bast Jr, RC: The CA 125 tumour-associated antigen: a review of the literatur. Hum Reprod 4: 1, 1989. Kabawat SE, Bast RC, Bahn A: Tissue distribution of a coelomic epithelium related antigen recognized by the monoclonal antibody OC 125. Lab Invest 48: 42A, 1983. Klug TL, Bast RC, Niloff JM et al: Monoclonal antibody immunoradiometric assay for an antigen with human epithelial ovarian cancer. Cancer Res 44: 1048, 1984. Pittaway DE, Fayez JA: Serum CA 125 levels increase during menses. Am J Obstet Gynecol56: 75,1987. Pittaway DE, Fayez JA: The use of CA 125 in the diagnosis and management of endometriosis. Fertil Steril 46: 790,1986. Zurawski VR, Broderick SF, Pickens P, et al: Serum CA 125 levels in a group of nonhospitalized women: relevance for the early detection of ovarian cancer. Obstet Gynecol 69: 606,1987.
Address for reprints: S. Graoberg Department of Obstetrics and Gynecology University of ateborg S-41345 GtHeborg, Sweden
1990,33: 149-152 International Federation of Gynecology and Obstetrics
149
Tumor marker CA 125 level and ovarian volume at different cycle day periods and in postmenopause S. Granberga, M.Wikland” and L.-G. Fribergb aDepartment of Obstetrics and Gynecology, bDepartment of Oncology, University of Giiteborg, Sahlgrenska sjukhuset, S-41345 Giiteborg (Sweden)
(Received March 23rd, 1989) (Revised and accepted July 26th, 1989)
Abstract The value of using CA 125 for screening of ovarian carcinoma is still under debate. It is important to be aware of possible physiological variation in serum levels of this antigen. This study aimed at finding out whether there were any differences in CA 125 levels in serum at different cycle day periods of fertile women and postmenopausal women. In IO6 women, CA 125 and ovarian volume were measured at different cycle day periods and in postmenopausal women. The highest levels were found in cycle day (CD) l-9, i.e. 22 units/ml and the lowest in postmenopausal women i.e. 6.7 units/ml. No correlation could be found between the CA 12.5 levels and ovarian volume as measured by vaginal sonography. Keywords: CA 125; Ovarian volume; Ultrasound. Introduction Ovarian cancer in women is the most common cause of death from gynecological malignancies. Early diagnosis of ovarian cancer has not improved despite the development of such technical tools as computer tomography (CT), ultrasound and magnetic resonance 0020-7292/90/$03.50
0 1990 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
(MR) [6, lo]. Today about 60% of ovarian cancers are discovered in stages III and IV, a figure that has not changed in the last 20 years [5,10,13]. Various antigens for epithelial tumors have been developed for use in the diagnosis of ovarian cancer and as an early indicator of recurrence of the cancer. One such is CA 125. It is a membrane antigen recognized by monoclonal antibody which was raised using an ovarian cancer cell line as an immunogen. It has been shown to be elevated in the serum of patients with serous epithelial ovarian carcinoma [1,2,7,17]. Bast and coworkers [ 1,2] found that 82% of women with epithelial ovarian carcinomas had increased CA 125 levels. On the other hand, 6% of patients with non-malignant diseases and 1% of healthy women also had elevated CA 125 values [ 1,2,7,17]. Pittaway and co-workers [lg] found differences in CA 125 levels with regard to the time before and after menstruation. This study was aimed at finding out whether there were any differences in CA 125 levels in serum at different cycle day periods of fertile women and postmenopausal women. These levels were then correlated to the ovarian volume. Materials and methods The study included 106 women between 22 Clinical and Clinical Research
150
Granberg et al.
and 76 years of age, who were close relatives of women who had or had had ovarian cancer. Seventy-one women were still menstruating and had proven fertility and 35 women were post-menopausal. None of the women had any history of gynecological disease up to 1 month prior to the time when blood samples were taken and when the ultrasound was performed. Two of the post-menopausal women had mammarian cancer 8 years before the blood sample for CA 125 determination was taken. These women were excluded from the statistical analysis. Blood samples were taken by puncturing of a peripheral vein by use of a vacutainer (Becton, Dickinson Vacuteiner System, France). A radioimmunoassay technique for the monoclonal antibody tumor marker CA 125 was used and has been described elsewhere (ELSA-CA 125 International CIS , France) [ 1,171. Ovarian volume was measured by use of sonography as previously described by Goswamy [lo] and by our group [11,12]. The transabdominal scans were performed using a transabdominal mechanical sector transducer of 3.5 MHz (Diasonic DRFlOO, Mil-pitas CA, USA). The transabdominal scans were performed using the full urinary bladder technique. The endovaginal scans were performed using an endovaginal transducer (Briiel & Kjaer, Naerum, Denmark). This mechanical sector transducer has a 112O sector and 7.5 MHz crystals. The focal length is 6 cm. The women were divided into two groups, menstruating and post-menopausal. The menstruating women were further divided into cycle day periods depending on the day in the cycle the blood sample was taken. The men-
Table I.
strual cycle length for the last 6 months was registerd. The mean was 28 days and the range 26-33 days. The menstrual cycles were grouped into the following periods CD l-9, lo-16 and 17-28. Statistics Mean f SD were calculated for each cycle day periods with regard to CA 125 serum levels and ovarian volume. Linear regression was used for the correlation calculations. For statistical comparison between groups Student’s t-test was used. Results Seventy-one women (68%) had CA 125 values less than 6.5 units/ml and ten women (10%) had values greater than 25 units/ml (Table I). The mean value for menstruating women was 13.6 f 8 units/ml and for postmenopausal women 6.7 f 1 units/ml. The two women with earlier known but treated mammarian cancer had values greater than 35 units/ml. Both these women had normal sized ovaries. CA 125 values during CD l-9 were statistically significantly higher as compared to CD lo-16 and CD 17-28 (P < 0.05). The mean values obtained during CD l-9 and CD lo16 were also significantly higher as compared to postmenopausal values (P < 0.05) (Table II). The mean values of CA 125 serum levels and ovarian volume at different cycle day periods and postmenopause are shown in Table II. No correlation was found between
Number of women at a given cycle day period (CD) and in postmenopause related to level of CA 125.
CA 125 (units/ml)
CD 1-9
CD lo-16
CD 17-28
Postmenopause
Total
< 6.5 6.6-25 >25
2 9 6
20 11 2
17 4 -
32 1 2=
71 25 8
“These two women were excluded from statistical evaluation, see text. Int J Gynecol Obstet 33
CA 125 levels and ovarian volume Table II.
CA 125 serum levels and ovarian
volume at different
Cycle day period
No. of women
Ovarian
l-9 lo-16 17-28 Postmenopause
17 33 21 33(+2)b
3.1 5.8 3.0 1.4
a Mean and SD. bThese two women were excluded
cycle day period and in menopause.
volume”
(cm))
from statistical
2 f k k
2.2 2.9 2.1 1.0
evaluation,
151
CA 125” (units/ml) 22.0 10.2 8.5 6.7
r 12.6 + 6.2 f 5.2 k 1.0
see text.
the CA 125 serum levels and ovarian volume at the different cycle day periods as well as between these parameters in the postmenopause. No postmenopausal woman had CA 125 values greater than 25 units/ml. In the group of menstruating women, eight had CA 125 serum levels above 25 units/ml (see Table I). Dikussion Measurement of CA 125 in blood is a method that has been claimed to be a valuable tool for early diagnosis of non-mutinous epithelial ovarian tumors. However, the value of the method for screening of ovarian carcinoma is still under debate. When using CA 125, it is important to be aware of possible physiological variation in serum levels of this antigen. It is known that CA 125 levels increase during menstruation [18] and in women with endometriosis [3,8,19]. Since the knowledge about CA 125 serum levels in different periods of the menstrual cycle of proven fertile women is very meager, this study was undertaken. Since it is known that there is a correlation between the ovarian volume and the steroid production of the ovary in different cycle day periods it would be of interest to see if such a correlation also could be found in the CA 125 levels. This would then indicate a relation between the steroid production of the ovary and CA 125 production or release. Such a relation has in fact been suggested by the in vitro studies by Bischef and co-workers [4]. Our results showed a maximal CA 125 level
in cycle day period l-9 (22.0 units/ml), whereafter there was a decrease to 10.2 units/ mlinCD10-l6andto8.5units/mlinCD17 -28. The maximal volume of the ovaries was found in the period CD lo-16 which of course is expected due to follicular development. However, there was no correlation between the size of the ovary and the CA 125 serum levels. It could be argued that the increase of estradiol and progesterone in some way influence the production or release of CA 125 since the levels reach maximal values at that time of the cycle when the production of these steroids are at their lowest. It has earlier been shown that CA 125 can be detected in adult tissues, in the fallopian tubes, endometrium and endocervix [ 16,201. The higher CA 125 levels during CD l-9 could thus also be explained by a leakage of CA 125 from the endometrium, as in women with endometriosis [3,8], to the peripheral circulation during the early follicular period of the cycle. Whether this is due to change in the synthesis or a change in the tissue barrier is not known. Due to the fact that laparoscopy was not performed in the women in this study, endometriosis cannot be excluded to be responsible for the higher values found in CD l-9. Our results are comparable with those found by Zurawski and co-workers [20]. In a non-hospitalized population, they found a mean CA 125 level in menstruating women between 14.3 units/ml and 28.2 units/ml, and in postmenopausal women between 10.6 units/ml and 16.3 units/ml. When using CA 125 for detection of Clinical and Clinical Research
152
Granberg et al.
ovarian cancer in menstruating women, attention should be paid to the fact that the serum levels may vary depending not only on pathology in the ovaries but also to physiology of the menstrual cycle. If the blood sample is taken during the early follicular period and a high value is obtained, ultrasound examination of the ovaries could be of value [9,11,14]. Furthermore, if a value of 20 or more units/ ml is found in postmenopausal women, ultrasound may be of importance in excluding an ovarian tumor. Jacobs and co-workers [ 151 found that if ultrasound examination of the ovaries was added to CA 125 measurements -in serum of postmenopausal women, the specificity of the examination increased to nearly 100% when screening for ovarian cancer [ 151. Ultrasound in combination with CA 125 measurement could thus be important when dealing with women at risk for ovarian cancer.
6
7
8
9
10 11
12
13 14
Acknowledgments We are grateful to The King Gustav V Jubilee Cancer Research Foundation in Gothenburg, Goteborg Medical Society and Brtiel and Kjaer, Naerum, Denmark for supporting this study. References Bast RC, Klug TL, Schaetzl E et al: Monitoring human ovarian carcinoma with combination of CA 125, CA 199, and carcinoembryonic antigen. Am J Obstet Gynecol 149: 553,1984. Bast RC, Klug TL, St John E et al: A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med 309: 883,1983. Barbieri RL, Niloff JM, Bast RC et al: Elevated serum concentrations of CA 125 in patients with advanced endometriosis. Fertil Steril45: 630, 1986. Bischof P, Tseng L, Briosch PA, Herrmann WL: Cancer antigen 125 is produced by human endometrial stroma cells. Hum Reprod 1: 423, 1986. Cancer incidence in Sweden 1983. National Board of Health and Wellfare. The Cancer Registery, 1987.
Int J Gynecol Obstet 33
15 16
17
18 19
20
Dembo AJ, Bush R, Beale F: The Princess Margaret Hospital study of ovarian cancer stage I, 11 and asymtomatic III. Cancer Treat Rep 63: 249, 1979. Einhorn N, Bast RC, Knapp RC et al: Preoperative evaluation of serum CA 125 levels in patients with primary epithelial ovarian cancer. Obstet Gynecol67: 414, 1986. Fedele L, Vercellini P, Arcaini L et al: CA 125 in serum, peritoneal fluid, active lesions, and endometrium of patients with endometriosis. Am J Obstet Gynecol 158: 166, 1988. Finkler NJ, Benacerraf B, Lavin PT et al: Comparison of serum CA 125, clinical impression, and ultrasound in the preoperative evaluation of ovarian masses. Obstet Gyneco1 72: 659, 1988. Goswamy RH, Cambell S, Whithead MJ: Screening for ovarian cancer. Clin Obstet Gynecol 10: 1, 1983. ‘Granberg S, Wikland M: A comparison between ultrasound and gynaecologic examination for detection of enlarged ovaries in a group of women at risk for ovarian carcinoma. J Ultrasound Med 7: 59,1988. Granberg S, Wikland M: Comparison between endovaginal and transabdominal transducer for measuring ovarian volume. J Ultrasound Med 6: 649, 1987. Incidence of Cancer in Norway 1985. The Cancer Registery of Norway, Oslo, 1987. Jacobs I, Bridges J, Reynolds C et al: Multimodal approach to screening for ovarian cancer. Lancet I: 268, 1988. Jacobs I, Bast Jr, RC: The CA 125 tumour-associated antigen: a review of the literatur. Hum Reprod 4: 1, 1989. Kabawat SE, Bast RC, Bahn A: Tissue distribution of a coelomic epithelium related antigen recognized by the monoclonal antibody OC 125. Lab Invest 48: 42A, 1983. Klug TL, Bast RC, Niloff JM et al: Monoclonal antibody immunoradiometric assay for an antigen with human epithelial ovarian cancer. Cancer Res 44: 1048, 1984. Pittaway DE, Fayez JA: Serum CA 125 levels increase during menses. Am J Obstet Gynecol56: 75,1987. Pittaway DE, Fayez JA: The use of CA 125 in the diagnosis and management of endometriosis. Fertil Steril 46: 790,1986. Zurawski VR, Broderick SF, Pickens P, et al: Serum CA 125 levels in a group of nonhospitalized women: relevance for the early detection of ovarian cancer. Obstet Gynecol 69: 606,1987.
Address for reprints: S. Graoberg Department of Obstetrics and Gynecology University of ateborg S-41345 GtHeborg, Sweden