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A study of the monoclonal antibody OC 125 to diagnose malignant ovarian tumors
GYNECOLOGIC
ONCOLOGY
32, 327-330 (1989)
A Study of the Monoclonal Antibody OC 125 to Diagnose Malignant Ovarian Tumors Lr XINGUO,
M.S. ,* CHEN DIXIA, M.D., * PETER E. SCHWARTZ, M.D.,?’
*Department of Obstetrics and Gynecology, First Afiliated Hospital, Hunan Medical fDepartment of Obstetrics & Gynecology, Yale University School of Medicine,
University, 333 Cedar
AND YANG ZHAN, M.D.* Changsha, People’s Street, New Haven,
Republic Connecticut
of China, 06510
and
Received August 3 1, 1987
Serum CA 125 was assayed preoperatively in 40 patients with ovarian malignancies and in 44 normal individuals. The correlation between CA 125 and tumor histology, tumor burden, ascites, and the clinical stage was analyzed. CA 125 levels greater than 65 U/ml were defined as positive. The results revealed normal values in each of the 44 normal individuals. CA 125 was elevated in 35 of 40 (87.5%) patients with malignant ovarian tumors including 23 of 24 (95.8%) patients with epithelial ovarian cancers, 7 of whom had stage I disease. Serum CA 125 was also elevated in 12 of 16 (75%) patients with nonepithelial ovarian malignancies. The results suggest that the CA 125 level can be correlated with tumor histology, tumor burden, and ascites but not with clinical stage. 0 1989 Academic Press, Inc. INTRODUCTION
The production of monoclonal antibodies has opened up a most promising field for the diagnosis and treatment of malignancies [ 1j. Studies using monoclonal antibodies to diagnose malignancies have developed rapidly in the past few years. Ovarian cancer ranks first in mortality from gynecological malignancies and has become the most life-threatening female pelvic reproductive organ tumor. A monoclonal antibody (OC 125) has been developed by somatic hybridization of spleen cells (from mice immunized with an epithelial ovarian carcinoma cell line (OVCA 433) [2]. The antigenic determinant measured by this antibody is called CA 125. In 1983, Bast et al. first reported the clinical use of the OC 125 [3]. Since then, additional reports concerning the clinical value of OC 125 have been published [4-lo]. However, problems in the use and interpretation of this assay remain. For example, do serum CA 125 assays have any value for diagnosing early stage epithelial ovarian cancers? Can CA 125 values be used to diagnose other histologic types of malignant ovarian ’ To whom correspondence
should be addressed.
tumors? Do CA 125 values reflect tumor burden or the presence or absence of ascites? There are few reports on the correlation between the CA 125 level and clinical stage, histologic type, tumor burden, or ascites. This investigation was undertaken to evaluate the role of CA 125 in diagnosing malignant ovarian tumors and to study the above-mentioned questions. METHODS
Serum samples from 44 healthy blood donors were obtained from the Blood Bank of the First Affiliated Hospital of the Hunan Medical University. Each donor had a normal physical examination and liver function tests. Blood samples were drawn preoperatively from 40 patients with newly diagnosed malignant ovarian tumors in the Changsha region. Blood was transported within 3 hr to our research unit where the serum was separated, frozen, and stored at - 20°C. The median age of the patients was 41.8 + 14.7 years (x -C SD). Twenty-four tumors were epithelial ovarian cancers (7 stage I, 1 stage II, 9 stage III, and 7 stage IV) and 16 were other types of ovarian malignant tumors (7 germ cell tumors, 2 sex cord stromal tumors, and 7 metastatic tumors). The immunoradiometric assay for CA 125 was performed as previously described by Bast et al. 131.Serum was diluted and reassayed when CA 125 levels exceeded 500 U/ml. CA 125 RIA kits were provided by Centocor, Inc., Malveme, Pennsylvania. Diagnoses were confirmed by review of the operative notes and pathology reports. Histological typing was according to the standard of FIG0 (1974). The burden of tumor was expressed by the maximum ovarian tumor diameter determined by preoperative ultrasound examinations and was divided into two groups, those less than 20 cm and those greater than 20 cm. The presence of ascites was determined by a review of the 327 0090~8258/89 $1.50 Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.
328
LI ET AL.
ultrasound reports and the operative records. A CA 125 value greater than 65 U/ml was defined as positive. CA 125 values are shown according to a logarithmic normal distribution as their degree of dispersion is high. All CA 125 values were transformed into logarithmic value before statistical analyses. The Student t test was chosen to test the significance of CA 125 values in the study groups. RESULTS The CA 125 values of each of the 44 healthy donors was less than 65 U/ml (Fig. 1). The 95% confidence interval was from 17 to 20 U/ml (z 4 to&z’) x SE). Serum CA 125 values above 65 U/ml were found in 35 of 40 (87.5%) patients with malignant ovarian tumors (Fig. 1, Table 1). The 95% confidence interval was from 258 to 697 U/ml (x + t,&n’) x SE). In patients with epithelial ovarian carcinomas, the CA 125 positivity rate was 95.8%. The CA 125 values in each of seven stage I patients were positive. Serum CA 125 was also elevated in 12 of 16 (75%) patients with nonepithelial ovarian malignancies. The CA 125 mean level (mean + SE, natural value) in 24 patients with epithelial ovarian cancers was significantly higher than that in 16 patients with other types of malignant ovarian tumors (Table 2). Elevated levels of CA 125 were found in each of 16 patients with serous cancers, 5 of 6 with mutinous cancers and 12 of 16 with other types of malignant ovarian neoplasms (Table 1). The serum CA 125 values were significantly greater (P
I04 [
. ?. 8 103 : -1 -- i E 2a ia l .
.
. . ; .
5 8 102
:
65 I---
_________
:
t .___..__________-__-------..
+
FIG. 1. Preoperative serum CA 125 values in normal women and patients with malignant ovarian tumors.
TABLE 1 CA 125 Levels in Malignant Ovarian Tumors CA 125 level >65 U/ml Disease
Total no. tested
No.
%
16 6 1 1
16 5 1 1
100
5 1 1
2 1 1
1 1
1 1
6 1
6 0
40
35
Epithelial tumors Serous Mutinous Mesothehal Mesodermal Germ cell tumors Immature teratoma Dysgerminoma Endodermal sinus cancer Sex cord stroma tumors Granulosa cell tumor Malignant thecal cell tumor Metastatic tumors Krukenberg tumor Lymphosarcoma Total
87.5
< 0.01) in 19 patients with ascites than in the 21 patients without ascites (Table 2). Two of five patients with immature teratomas (one stage I, one stage II) with ascites had elevated CA 125 values, the values being 76 and 255 U/ml, respectively; in three patients without ascites the CA 125 values were within the normal range (25, 28, and 30 U/ml). The CA 125 values for 9 of 24 patients with epithelial ovarian cancers with maximum tumor diameters 220 cm were significantly greater than those of 15 patients with maximum tumor diameters <20 cm. (P < 0.05). Statistical analysis failed to demonstrate a significant correlation between CA 125 levels and clinical stage (Table 3). DISCUSSION Serum CA 125 assays provide a useful clinical marker for diagnosing all histological types of epithelial ovarian cancer. Elevated serum CA 125 levels were identified not only in patients with nonmucinous epithelial tumors but also in five of six patients with mutinous epithelial tumors in this study. This observation is inconsistent with earlier immunohistochemical studies of tissue sections in which no CA 125 antigen could be found in mutinous epithelial tumors [ll]. Epithelial cancers are the most common forms of ovarian malignancies in China, where they account for 60 to 70% of malignant ovarian tumors [12]. The high sensitivity for ovarian epithelial cancer lends credence to the assay’s value in diagnosing ovarian malignancies and improving their prognosis.
OC 125 TO DIAGNOSE
MALIGNANT TABLE
OVARIAN
329
TUMORS
2
Correlation between CA 125 Level and Tumor Type or Ascites x rfr SE (U/ml) (logarithmic values)
No.
Group
Epithelial Nonepithelial Ascites present Ascites absent
24
16 19 21
B (U/ml) (natural value)
95% Confidence interval” (natural value U/ml)
P
2.879 2.249
t 0.127 ? 0.147
757 177
413-1387 88-365
<0.0025
2.900 2.380
f
_’ 0.144
794 238
407-1549 12-79
0.138
’ 95% confidence interval is expressed with x k to.&‘)
x SE.
The CA 125 assay can diagnose ovarian cancer at an early stage. Each of seven patients in the present study with stage I disease had a CA 125 value greater than 65 U/ml. Monoclonal antibodies are noted for their high specificity and sensitivity. The radioimmunoassay is a trace assay and its sensitivity can reach lo-*’ g. Thus it is possible that elevated serum CA 125 levels can be identified in patients with earlier stages of disease. It has yet to be conclusively demonstrated whether serum CA 125 is capable of diagnosing nonepithelial ovarian malignant tumors. The finding in the present study of elevated serum CA 125 levels from 12 of 16 (75%) patients with other types of malignant ovarian tumors is inconsistent with earlier studies of tissue section by Kabawat et al. [ll]. Kabawat et al. failed to detect CA 125 in sections from germ cell and sex cord-stromal tumors [I 11. Additional clinical data are necessary before a conclusion may be drawn. A significant correlation was found between CA 125 levels and the burden of ovarian cancer. The mean concentration in patients with tumor diameters 220 cm was greater than that of the patients with tumor diameters ~20 cm (P < 0.05). It has been reported that CA 125 levels in some patients during treatment correlate with tumor burden. Our data confirm that the serum CA 125 levels may be correlated with the preoperative tumor burden. Statistical analysis failed to demonstrate a correlation between CA 125 levels and clinical staging in 24 patients with epithelial ovarian cancers (P > 0.05). The clinical TABLE
stage reflects mainly the metastatic extension but not the number of cancer cells directly. Sometimes, the tumor burden is very large while the clinical stage is still earlier. Therefore, CA 125 levels may seem inconsistent with clinical stage. There is no report comparing the relationship between serum CA 125 levels and the presence of ascites. In the present series the mean serum CA 125 concentration of 19 patients with ascites was greater than that of 21 patients without ascites (P < 0.01). What was more interesting was that 2 of 5 patients with immature teratomas and ascites had elevated serum CA 125 values whereas 3 patients without ascites had a normal serum CA 125 value. Kabawat et al. [13] found tl# CA 125 antigen was present in the mesothelial cells lining the adult pleura, pericardium, and peritoneum, especially in areas of inflammation and adhesions and considered that the occurrence of pleuritis or peritonitis in patients with tumor metastases may facilitate absorption of CA 125 from the serosal cavities or may increase the number of positive mesothelial cells that enlarge and proliferate as a response to inflammation. This might be the mechanism explaining why patients with ascites had elevated CA 125 levels.
ACKNOWLEDGMENTS We are indebted to Professor Yao Kaitai for his valuable advice regarding statistical analysis of the data and to Professor Zhang Zhihua for providing excellent technical assistance.
3
Correlation between CA 125 Levels and Tumor Burden or Clinical Stage x 2 SE (U/ml) (logarithmic values)
X (U/ml) (natural value)
2.710 f+ 0.163 0.177
513 1442
229-1148 565-3681
402 982
493-1954
Group
No.
Tumor burden (cm) ~20 Tumor burden (cm) a20
1.5 9
3.159
Stage I Stage II-IV
177
2.604 2.992
2 0.258 It 0.141
y 95% confidence interval is expressed with X + to.&‘)
x
SE.
95% Confidence interval” (natural value U/ml)
94-1718
P co.05 >0.05
330
LI ET AL.
REFERENCES 1. Kohler, G., and Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity, Natwe (London) 256, 495 (1975). 2. Bast, R. C., Feeney, M., Lazarus, H., et al. Reactivity of a monoclonal antibody with human ovarian carcinoma, .I. Clin. Invest. 68, 1331 (1981). 3. Bast, R. C., Klug, T. L., John, E., et al. A radioimmunassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer, N. EngI. J. Med. 309, 883 (1983). 4. Klug, T. L., Bast, R. C., Niloff, J. M., et al. Monoclonal antibody immunoradiometric assay for an antigenic determinant (CA 125) associated with human epithelial ovarian carcinomas, Cancer Res. 44, 2813 (1984). 5. Lian, L., Hu, X., Liu, W., et al. The monoclonal antibody RIA for an antigenic determinant CA 125 in ovarian cancer patients, Chin. J. Obstet. Gynecol. 20, 257 (1985). 6. Ricolleau, G., Chatal, J. F., Fumoleau, P., et al. Radioimmunoassay of the CA 125 antigen in ovarian carcinomas: Advantages compared with CA 19-9 and CEA, Tumor Biol. 5, 151 (1984). 7. Wood, W. G., and Werner, A. CEA, TPA and CA 125 levels in
different patient groups with benign and malignant disease, Aertzl. Lab. 30, 309 (1984). Saitoh, S., Nakanishi, A., Noda, R., et al. Clinical usefulness of *. monoclonal antibody CA 125 and CA 19-9 in ovarian cancer, J. Japan. Sot. Cancer Ther. 19, 2327 (1984). 9. Kimura, E., Murae, M., Koga, R., et al. Clinical significance of the new tumor marker CA 125 in gynecological cancer particularly usefulness in diagnosis of ovarian cancer, Acta Obstet. Gynecol. Jupon. 36, 2121 (1984). 10. Kazuo, K., Tutomu, C., Yutaka, A., et al. A new serum tumor marker of ovarian cancer, Lgaku No Ayumi 129, 327 (1984). 11. Kabawat, S. E., Bast, R. C., Welch, W. R., et al. Immunopathologic characterization of a monoclonal antibody that recognizes common surface antigens of human ovarian tumors of serous, endometrioid and clear cell types, Amer. J. Clin. Purhol. 79, 98 (1983). 12 Zheng, H., Su, Y., et al. Obstetrics and gynecology, The Peoples Health Printing Co., Beijing, p. 306 (1984). 13. Kabawat, S. E., Bast, R. C., Bhan, A. K., et al. Tissue distribution of a coelomic epithelium related antigen recognized by the monoclonal antibody OC 125, Znt. J. Gynecol. Pathol. 2, 275 (1983).
ONCOLOGY
32, 327-330 (1989)
A Study of the Monoclonal Antibody OC 125 to Diagnose Malignant Ovarian Tumors Lr XINGUO,
M.S. ,* CHEN DIXIA, M.D., * PETER E. SCHWARTZ, M.D.,?’
*Department of Obstetrics and Gynecology, First Afiliated Hospital, Hunan Medical fDepartment of Obstetrics & Gynecology, Yale University School of Medicine,
University, 333 Cedar
AND YANG ZHAN, M.D.* Changsha, People’s Street, New Haven,
Republic Connecticut
of China, 06510
and
Received August 3 1, 1987
Serum CA 125 was assayed preoperatively in 40 patients with ovarian malignancies and in 44 normal individuals. The correlation between CA 125 and tumor histology, tumor burden, ascites, and the clinical stage was analyzed. CA 125 levels greater than 65 U/ml were defined as positive. The results revealed normal values in each of the 44 normal individuals. CA 125 was elevated in 35 of 40 (87.5%) patients with malignant ovarian tumors including 23 of 24 (95.8%) patients with epithelial ovarian cancers, 7 of whom had stage I disease. Serum CA 125 was also elevated in 12 of 16 (75%) patients with nonepithelial ovarian malignancies. The results suggest that the CA 125 level can be correlated with tumor histology, tumor burden, and ascites but not with clinical stage. 0 1989 Academic Press, Inc. INTRODUCTION
The production of monoclonal antibodies has opened up a most promising field for the diagnosis and treatment of malignancies [ 1j. Studies using monoclonal antibodies to diagnose malignancies have developed rapidly in the past few years. Ovarian cancer ranks first in mortality from gynecological malignancies and has become the most life-threatening female pelvic reproductive organ tumor. A monoclonal antibody (OC 125) has been developed by somatic hybridization of spleen cells (from mice immunized with an epithelial ovarian carcinoma cell line (OVCA 433) [2]. The antigenic determinant measured by this antibody is called CA 125. In 1983, Bast et al. first reported the clinical use of the OC 125 [3]. Since then, additional reports concerning the clinical value of OC 125 have been published [4-lo]. However, problems in the use and interpretation of this assay remain. For example, do serum CA 125 assays have any value for diagnosing early stage epithelial ovarian cancers? Can CA 125 values be used to diagnose other histologic types of malignant ovarian ’ To whom correspondence
should be addressed.
tumors? Do CA 125 values reflect tumor burden or the presence or absence of ascites? There are few reports on the correlation between the CA 125 level and clinical stage, histologic type, tumor burden, or ascites. This investigation was undertaken to evaluate the role of CA 125 in diagnosing malignant ovarian tumors and to study the above-mentioned questions. METHODS
Serum samples from 44 healthy blood donors were obtained from the Blood Bank of the First Affiliated Hospital of the Hunan Medical University. Each donor had a normal physical examination and liver function tests. Blood samples were drawn preoperatively from 40 patients with newly diagnosed malignant ovarian tumors in the Changsha region. Blood was transported within 3 hr to our research unit where the serum was separated, frozen, and stored at - 20°C. The median age of the patients was 41.8 + 14.7 years (x -C SD). Twenty-four tumors were epithelial ovarian cancers (7 stage I, 1 stage II, 9 stage III, and 7 stage IV) and 16 were other types of ovarian malignant tumors (7 germ cell tumors, 2 sex cord stromal tumors, and 7 metastatic tumors). The immunoradiometric assay for CA 125 was performed as previously described by Bast et al. 131.Serum was diluted and reassayed when CA 125 levels exceeded 500 U/ml. CA 125 RIA kits were provided by Centocor, Inc., Malveme, Pennsylvania. Diagnoses were confirmed by review of the operative notes and pathology reports. Histological typing was according to the standard of FIG0 (1974). The burden of tumor was expressed by the maximum ovarian tumor diameter determined by preoperative ultrasound examinations and was divided into two groups, those less than 20 cm and those greater than 20 cm. The presence of ascites was determined by a review of the 327 0090~8258/89 $1.50 Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.
328
LI ET AL.
ultrasound reports and the operative records. A CA 125 value greater than 65 U/ml was defined as positive. CA 125 values are shown according to a logarithmic normal distribution as their degree of dispersion is high. All CA 125 values were transformed into logarithmic value before statistical analyses. The Student t test was chosen to test the significance of CA 125 values in the study groups. RESULTS The CA 125 values of each of the 44 healthy donors was less than 65 U/ml (Fig. 1). The 95% confidence interval was from 17 to 20 U/ml (z 4 to&z’) x SE). Serum CA 125 values above 65 U/ml were found in 35 of 40 (87.5%) patients with malignant ovarian tumors (Fig. 1, Table 1). The 95% confidence interval was from 258 to 697 U/ml (x + t,&n’) x SE). In patients with epithelial ovarian carcinomas, the CA 125 positivity rate was 95.8%. The CA 125 values in each of seven stage I patients were positive. Serum CA 125 was also elevated in 12 of 16 (75%) patients with nonepithelial ovarian malignancies. The CA 125 mean level (mean + SE, natural value) in 24 patients with epithelial ovarian cancers was significantly higher than that in 16 patients with other types of malignant ovarian tumors (Table 2). Elevated levels of CA 125 were found in each of 16 patients with serous cancers, 5 of 6 with mutinous cancers and 12 of 16 with other types of malignant ovarian neoplasms (Table 1). The serum CA 125 values were significantly greater (P
I04 [
. ?. 8 103 : -1 -- i E 2a ia l .
.
. . ; .
5 8 102
:
65 I---
_________
:
t .___..__________-__-------..
+
FIG. 1. Preoperative serum CA 125 values in normal women and patients with malignant ovarian tumors.
TABLE 1 CA 125 Levels in Malignant Ovarian Tumors CA 125 level >65 U/ml Disease
Total no. tested
No.
%
16 6 1 1
16 5 1 1
100
5 1 1
2 1 1
1 1
1 1
6 1
6 0
40
35
Epithelial tumors Serous Mutinous Mesothehal Mesodermal Germ cell tumors Immature teratoma Dysgerminoma Endodermal sinus cancer Sex cord stroma tumors Granulosa cell tumor Malignant thecal cell tumor Metastatic tumors Krukenberg tumor Lymphosarcoma Total
87.5
< 0.01) in 19 patients with ascites than in the 21 patients without ascites (Table 2). Two of five patients with immature teratomas (one stage I, one stage II) with ascites had elevated CA 125 values, the values being 76 and 255 U/ml, respectively; in three patients without ascites the CA 125 values were within the normal range (25, 28, and 30 U/ml). The CA 125 values for 9 of 24 patients with epithelial ovarian cancers with maximum tumor diameters 220 cm were significantly greater than those of 15 patients with maximum tumor diameters <20 cm. (P < 0.05). Statistical analysis failed to demonstrate a significant correlation between CA 125 levels and clinical stage (Table 3). DISCUSSION Serum CA 125 assays provide a useful clinical marker for diagnosing all histological types of epithelial ovarian cancer. Elevated serum CA 125 levels were identified not only in patients with nonmucinous epithelial tumors but also in five of six patients with mutinous epithelial tumors in this study. This observation is inconsistent with earlier immunohistochemical studies of tissue sections in which no CA 125 antigen could be found in mutinous epithelial tumors [ll]. Epithelial cancers are the most common forms of ovarian malignancies in China, where they account for 60 to 70% of malignant ovarian tumors [12]. The high sensitivity for ovarian epithelial cancer lends credence to the assay’s value in diagnosing ovarian malignancies and improving their prognosis.
OC 125 TO DIAGNOSE
MALIGNANT TABLE
OVARIAN
329
TUMORS
2
Correlation between CA 125 Level and Tumor Type or Ascites x rfr SE (U/ml) (logarithmic values)
No.
Group
Epithelial Nonepithelial Ascites present Ascites absent
24
16 19 21
B (U/ml) (natural value)
95% Confidence interval” (natural value U/ml)
P
2.879 2.249
t 0.127 ? 0.147
757 177
413-1387 88-365
<0.0025
2.900 2.380
f
_’ 0.144
794 238
407-1549 12-79
0.138
’ 95% confidence interval is expressed with x k to.&‘)
x SE.
The CA 125 assay can diagnose ovarian cancer at an early stage. Each of seven patients in the present study with stage I disease had a CA 125 value greater than 65 U/ml. Monoclonal antibodies are noted for their high specificity and sensitivity. The radioimmunoassay is a trace assay and its sensitivity can reach lo-*’ g. Thus it is possible that elevated serum CA 125 levels can be identified in patients with earlier stages of disease. It has yet to be conclusively demonstrated whether serum CA 125 is capable of diagnosing nonepithelial ovarian malignant tumors. The finding in the present study of elevated serum CA 125 levels from 12 of 16 (75%) patients with other types of malignant ovarian tumors is inconsistent with earlier studies of tissue section by Kabawat et al. [ll]. Kabawat et al. failed to detect CA 125 in sections from germ cell and sex cord-stromal tumors [I 11. Additional clinical data are necessary before a conclusion may be drawn. A significant correlation was found between CA 125 levels and the burden of ovarian cancer. The mean concentration in patients with tumor diameters 220 cm was greater than that of the patients with tumor diameters ~20 cm (P < 0.05). It has been reported that CA 125 levels in some patients during treatment correlate with tumor burden. Our data confirm that the serum CA 125 levels may be correlated with the preoperative tumor burden. Statistical analysis failed to demonstrate a correlation between CA 125 levels and clinical staging in 24 patients with epithelial ovarian cancers (P > 0.05). The clinical TABLE
stage reflects mainly the metastatic extension but not the number of cancer cells directly. Sometimes, the tumor burden is very large while the clinical stage is still earlier. Therefore, CA 125 levels may seem inconsistent with clinical stage. There is no report comparing the relationship between serum CA 125 levels and the presence of ascites. In the present series the mean serum CA 125 concentration of 19 patients with ascites was greater than that of 21 patients without ascites (P < 0.01). What was more interesting was that 2 of 5 patients with immature teratomas and ascites had elevated serum CA 125 values whereas 3 patients without ascites had a normal serum CA 125 value. Kabawat et al. [13] found tl# CA 125 antigen was present in the mesothelial cells lining the adult pleura, pericardium, and peritoneum, especially in areas of inflammation and adhesions and considered that the occurrence of pleuritis or peritonitis in patients with tumor metastases may facilitate absorption of CA 125 from the serosal cavities or may increase the number of positive mesothelial cells that enlarge and proliferate as a response to inflammation. This might be the mechanism explaining why patients with ascites had elevated CA 125 levels.
ACKNOWLEDGMENTS We are indebted to Professor Yao Kaitai for his valuable advice regarding statistical analysis of the data and to Professor Zhang Zhihua for providing excellent technical assistance.
3
Correlation between CA 125 Levels and Tumor Burden or Clinical Stage x 2 SE (U/ml) (logarithmic values)
X (U/ml) (natural value)
2.710 f+ 0.163 0.177
513 1442
229-1148 565-3681
402 982
493-1954
Group
No.
Tumor burden (cm) ~20 Tumor burden (cm) a20
1.5 9
3.159
Stage I Stage II-IV
177
2.604 2.992
2 0.258 It 0.141
y 95% confidence interval is expressed with X + to.&‘)
x
SE.
95% Confidence interval” (natural value U/ml)
94-1718
P co.05 >0.05
330
LI ET AL.
REFERENCES 1. Kohler, G., and Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity, Natwe (London) 256, 495 (1975). 2. Bast, R. C., Feeney, M., Lazarus, H., et al. Reactivity of a monoclonal antibody with human ovarian carcinoma, .I. Clin. Invest. 68, 1331 (1981). 3. Bast, R. C., Klug, T. L., John, E., et al. A radioimmunassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer, N. EngI. J. Med. 309, 883 (1983). 4. Klug, T. L., Bast, R. C., Niloff, J. M., et al. Monoclonal antibody immunoradiometric assay for an antigenic determinant (CA 125) associated with human epithelial ovarian carcinomas, Cancer Res. 44, 2813 (1984). 5. Lian, L., Hu, X., Liu, W., et al. The monoclonal antibody RIA for an antigenic determinant CA 125 in ovarian cancer patients, Chin. J. Obstet. Gynecol. 20, 257 (1985). 6. Ricolleau, G., Chatal, J. F., Fumoleau, P., et al. Radioimmunoassay of the CA 125 antigen in ovarian carcinomas: Advantages compared with CA 19-9 and CEA, Tumor Biol. 5, 151 (1984). 7. Wood, W. G., and Werner, A. CEA, TPA and CA 125 levels in
different patient groups with benign and malignant disease, Aertzl. Lab. 30, 309 (1984). Saitoh, S., Nakanishi, A., Noda, R., et al. Clinical usefulness of *. monoclonal antibody CA 125 and CA 19-9 in ovarian cancer, J. Japan. Sot. Cancer Ther. 19, 2327 (1984). 9. Kimura, E., Murae, M., Koga, R., et al. Clinical significance of the new tumor marker CA 125 in gynecological cancer particularly usefulness in diagnosis of ovarian cancer, Acta Obstet. Gynecol. Jupon. 36, 2121 (1984). 10. Kazuo, K., Tutomu, C., Yutaka, A., et al. A new serum tumor marker of ovarian cancer, Lgaku No Ayumi 129, 327 (1984). 11. Kabawat, S. E., Bast, R. C., Welch, W. R., et al. Immunopathologic characterization of a monoclonal antibody that recognizes common surface antigens of human ovarian tumors of serous, endometrioid and clear cell types, Amer. J. Clin. Purhol. 79, 98 (1983). 12 Zheng, H., Su, Y., et al. Obstetrics and gynecology, The Peoples Health Printing Co., Beijing, p. 306 (1984). 13. Kabawat, S. E., Bast, R. C., Bhan, A. K., et al. Tissue distribution of a coelomic epithelium related antigen recognized by the monoclonal antibody OC 125, Znt. J. Gynecol. Pathol. 2, 275 (1983).