GYNECOLOGIC
ONCOLOGY
37, 276-278 (1990)
Comparison between Squamous Cell Carcinoma-Associated Antigen and CA-125 in Patients with Carcinoma of the Cervix PENTTI LEHTOVIRTA,**’
LASSEVIINIKKA,t’$
AND OLAVI YLIKORKALA*
Departments of *Obstetrics and Gynecology and Whildren’s Hospital, Helsinki University Central Hospital, and Medical Research Institute Minerva, Helsinki, Finland Received September 6, 1989
carcinoma. In this work we compared the efficacy of
Serum levels of CA-125 and squamous cell carcinoma-associSCC antigen and CA-125 in detection of adenocarcinoma ated antigen (SCC) were measured in 30 patients with squamous and squamous cell carcinoma of the cervix. cell carcinoma and 12 patients with adenocarcinoma of the uterine cervix. SCC was elevated in 67% of patients with squamous cell PATIENTS AND METHODS carcinoma but in only 25% of patients with adenocarcinoma. In contrast, CA-125 was elevated in 75% of patients with adenoForty-two patients with biopsy-proven cervical cancer carcinoma but in only 26% of patients with squamous cell carwere studied (Table 1). Thirty patients had squamous cinoma. These data demonstrate the applicability of the measurement of CA-125 as a tumor marker for cervical cell carcinoma and twelve had adenocarcinoma. Before adenocarcinoma and confirm the value of the measurement of any treatment blood samples were drawn, and the sera SCC antigen in patients with cervical squamous cell carcinoma. of all patients were assayed for SCC antigen using a Moreover, we show that measurement of SCC antigen in ade- double-antibody radioimmunoassay (Abbott SCC-RIA, nocarcinoma and measurement of CA-125 in squamous cell car- Abbott Laboratories, Diagnostic Division, Abbott Park, cinoma are of insufficient clinical value. 0 I!390 Academic Press, Inc. North Chicago, IL). Levels above 2.0 rig/ml were con-
INTRODUCTION Squamous cell carcinoma-associated
antigen (SCC an-
tigen) is a subfraction of tumor antigen TA-4, which in 1977was purified from cervical squamous cell carcinoma [l]. It is a glycoprotein which is detected by immunohistochemical staining in all samples of malignant squamous cell neoplasms but only very rarely in normal glandular epithelium of the cervix [2]. SCC antigen is excreted into sera of patients with squamous cell carcinoma of the cervix, and its concentration in serum reflects the advance of the disease [3-51. It is well established that some lo-20% of cervical cancers are adenocarcinomas, and their proportion is increasing [6]. Yet almost nothing [5] is known of SCC antigen in cervical adenocarcinoma. Furthermore, the value of CA-125, a tumor marker used mainly for follow-up of epithelial ovarian carcinoma, has not been thoroughly assessed in the diagnosis of cervical ’ To whom reprint requests should be addressed: Departments of Obstetrics and Gynecology, Helsinki University Central Hospital, Haartmaninkatu 2, SF-00290 Helsinki, Finland.
sidered elevated, based on the data of our healthy controls (n = 20) and on those of the others [7]. In all but three patients with squamous cell cancer the levels of CA-125 were measured immunoradiometrically using commercial reagents (Abbott Laboratories, Wiesbaden, FRG). Levels above 35 IU/ml were considered elevated @I. Statistical analyses were carried out with the x2 test. RESULTS Twenty of thirty patients (67%) with cervical squamous cell carcinoma but only 3 of 12 patients (25%) with adenocarcinoma had elevated serum SCC antigen levels. This difference is statistically significant (P < 0.01). SCC antigen was raised in 50% of patients with stage I disease, as compared to 71 and to 82% of patients with stage II and III-IV disease (Fig. 1). Seven of twenty-seven patients (26%) with squamous cell carcinoma had elevated CA-125 levels, as compared to 9 of 12 patients (75%) with adenocarcinoma (Fig. 2). The difference is statistically significant (P < 0.01). Both markers were elevated in 22% and normal in 33% of
276 009%8258/90 $1.50 Copyright Q 1990 by Academic Press, Inc. All rights of reproductionin any form reserved.
CA-125 AND SCC LEVELS IN CERVICAL TABLE 1 Clinical Features of Patients with Carcinoma of the Cervix
Histology
Number of patients
Mean age in years (range)
30 12
64.0 (31-84) 64.7 (34-g5)
Squamous cell carcinoma Adenocarcinoma
1000
Clinical stage (FIGO) I
II
III-IV
12 7 6 4
11 2
patients with squamous cell carcinoma and in 25 and 25% of the patients with adenocarcinoma. Elevated SCC and normal CA-125 levels were found in 41% of patients with squamous cell carcinoma but in none of the patients with adenocarcinoma (P < 0.05). In contrast, elevated CA-125 and normal SCC levels were observed in 50% of patients with adenocarcinoma but only in 4% of patients with squamous cell carcinoma (P < 0.01) (Table
277
CANCER
I
0
“t*“., . l , . , ST
I
ST
II
ST III-IV
FIG. 2. Individual serum CA-125 levels in 27 patients with squamous cell carcinoma (0) and 12 patients with adenocarcinoma of the uterine cervix (0).
2).
DISCUSSION Cervical adenocarcinoma often grows inside the cervix and escapes detection by Pap smear [9]. Therefore, tumor markers detectable in the blood are needed to reveal the disease. Thus far, measurement of carcinoembryonic antigen (CEA) has been used for this purpose. Although preoperative plasma levels of CEA are more often elevated in patients with endocervical adenocarcinoma than in those with squamous cell carcinoma [lo-121, the lack
100~
0
0
8
:
l0
P :
10
-
b 5 I H
0
2.0 .--- ,i 4
1.0 0.5
8’ ----------
.0
0 l
I EL ST
j. ----- -mm----m-__
l
I
0%
0
of tumor specificity and tumor sensitivity of this antigen limits its diagnostic use [ 11,131.Also, CA-19-9 has shown to have inadequate sensitivity to justify use of this marker in patients with cervical cancer [13]. CA-125 is a differentiation antigen shared by Mtillerian derivates including the endocervix [14,15]. We show that CA-125 is elevated in 75% of patients with cervical adenocarcinoma, which means it might be applicable to the detection of this disease. Our result agrees well with earlier studies in which elevated levels of serum CA-125 were found in 57-83% of patients with primary cervical adenocarcinoma [ 16-181. Since the concentration of CA125 in cervical mucus is high in healthy subjects but decreased in patients with adenocarcinoma [19,20], its enhanced transfer from the endocervix into the circulation is a more likely mechanism for the raised level of blood CA-125 than its increased synthesis. Since SCC also exists in normal cervical squamous cells [21], it was expected that its transfer to blood may be enhanced during the malignant endocervical process. Our present data show, however, that this is not the
TABLE 2 Presence of Raised Levels of SCC and CA-125 in Patients with Epithelial and Adenomatous Carcinoma of the Cervix
0 0 ST
II
ST Ill-IV
FIG. 1. Individual serum SCC antigen levels in 30 patients with squamous cell carcinoma (0) and 12 patients with adenocarcinoma of the uterine cervix (0).
SCC/CA-125
Squamous cell carcinoma (%)
Adenocarcinoma (%)
Significance of the difference
Raised/raised Normal/normal Raised/normal Normal/raised
( 6127) 22 ( 9127) 33 (11/27) 41 ( l/27) 4
(3/12) 25 (3/12) 25
NS NS
W12~ 0
P < 0.05 P < 0.01
(6/12) 50
278
LEHTOVIRTA,
VIINIKKA,
case, and thus the measurement of SCC antigen is of no value in patients with cervical adenocarcinoma. This conclusion disagrees somewhat with the findings of Duk et al., who reported elevated SCC levels in 38% of patients with cervical adenocarcinoma, yet no relation to the stage of the disease was seen [18]. In accordance with a substantial amount of earlier data [3-5,7,22,23], SCC antigen is elevated in most patients with squamous cell carcinoma of the cervix in relation to the extent of the disease. The concentration of CA125 was elevated in only 26% of patients with squamous cell carcinoma, which is in full accord with the 20% reported by Senekjian et al. [7]. Thus, the measurement of CA-125 contributes little to the diagnosis of cervical squamous cell carcinoma. In conclusion, measurements of SCC antigen in squamous cell carcinoma and of CA-125 in adenocarcinoma of the cervix reveal about two-thirds of the patients. Their efficacy in revealing these diseases is thus of the same magnitude of many other tumor markers utilized in clinical practice. Their value may be limited in primary diagnosis, but most likely they are valuable in monitoring the course of these cancers. ACKNOWLEDGMENT The measurements of SCC antigen concentration were made in the Clinical Laboratory Medix (Espoo, Finland).
REFERENCES 1. Kato, H., and Torigoe, T. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma, Cancer 40, 1621-1628 (1977). 2. Flint, A., McCoy, J. P., Schade, W. J., Hotheinz, D. A., and Haines, H. G. Cervical carcinoma antigen: Distribution in neoplastic lesions of the uterine cervix and comparison to other tumor markers, Gynecol. Uncol. 30, 63-70 (1988). 3. Kato, H., Morioka, H., Tsutsui, H., Aramaki, S., and Torigoe, T. Value of tumor-antigen (TA-4) of squamous cell carcinoma in predicting the extent of cervical cancer, Cancer 50, 1294-1296 (1982). 4. Maruo, T., Shibata, K., Kimura, A., Hoshina, M., and Mochizuki, M. Tumor-associated antigen, TA-4, in the monitoring of the effects of therapy for squamous cell carcinoma of the uterine cervix, Cancer 56, 302-308 (1985). 5. Crombach, G., Wtirz, H., and Bolte, A. Bestimmung des SCCantigens in Serum von Patienten mit Zervixkarzinom, Geburrsh. Frauenheilk. 47, 439-445 (1987). 6. Brand, E., Berek, J. S., and Hacker, N. F. Controversies in the management of cervical adenocarcinoma, Obster. Gynecol. 71, 261-269 (1988). 7. Senekjian, E. K., Young. J. M., Weiser, P. A., Spencer, C. E., Magic, S. E., and Herbst, A. L. An evaluation of squamous cell carcinoma antigen in patients with cervical squamous cell carcinoma, Amer. J. Obstet. Gynecol. 157, 433-439 (1987). 8. Bast, R. C., Jr., Klug, T. L., St. John, E., Jenison, E., Niloff, J. M., Lazarus, H., Berkowitz, R. S., Leavitt, T., Griffith% T.,
AND YLIKORKALA Parker, L., Zurawski, V. R., Jr., and Knapp, R. C. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer, N. Engl. J. Med. 309, 883-887 (1983). 9. Korhonen, M. 0. Adenocarcinoma of the uterine cervix: An evaluation of the available diagnostic methods, Acta P&ho/. Microbial. Scnnd. A Suppl. 264, 3-51 (1978). 10. Rutanen, E.-M., Lindgren, J., Sipponen, P., Stenman, U.-H., Saksela, E., and Seppala, M. Carcinoembryonic antigen in malignant and nonmalignant gynecologic tumors. Circulating levels and tissue localization, Cancer 42, 581-590 (1978). 11. van Nagell, J. R., Jr., Donaldson, E. S., Gay, E. C., Rayburn, P., Powell, D. F., and Goldenberg, D. M. Carcinoembryonic antigen in carcinoma of the uterine cervix. 1. The prognostic value of serial plasma determinations, Cancer 42, 2428-2434 (1978). 12. van Nagell, J. R., Jr., Donaldson, E. S., Gay, E. C., Hudson, S., Sharkey, R. M., Primus, F. J., Powell, D. F., and Goldenberg, D. M. Carcinoembryonic antigen in carcinoma of the uterine cervix. 2. Tissue localization and correlation with plasma antigen concentration, Cancer 44, 944-948 (1979). 13. Schwartz, P. E., Chambers, S. K., Chambers, J. T., Gutmann, J., Katopodis, N., and Foemmel, R. Circulating tumor markers in the monitoring of gynecologic malignancies, Cancer 60, 353-361 (1987). 14. Kabawat, S. E., Bast, R. C., Jr., Bhan, A. K., Welch, W. R., Knapp, R. C., and Colvin, R. B. Tissue distribution of coelomicepithelium-related antigen recognized by the monoclonal antibody OC125, Int. J. Gynecol. Pathol. 2, 275-285 (1983). 15. Scharl, A., Crombach, G., Vierbuchen, M., Mtisch, H., and Bolte, A. CA-125 in normal tissues and carcinomas of the uterine cervix, endometrium and fallopian tube. I. Immunohistochemical detection, Arch. Gynecol. Obstet. 244, 103-112 (1989). 16. Niloff, J. M., Klug, T. L., Schaetzl, E., Zurawski, V. R., Knapp, R. C., and Bast, R. C., Jr. Elevation of serum CA-125 in carcinoma of the fallopian tube, endometrium, and endocervix, Amer. J. Obstet. Gynecol. 148, 1057-1058 (1984). 17. Crombach, G., Scharl, A., and Wtirz, H. CA-125 in normal tissues and carcinoma of the uterine cervix, endometrium and fallopian tube. II. Immunoradiometric determination in secretions, tissue extracts and serum, Arch. Gynecol. Obstet. 244, 113-122 (1989). 18. Duk, J. M., Aalders, J. D., Fleuren, G. J., Krans, M., and de Bruijn, H. W. A. Tumor markers CA-125, squamous cell carcinoma antigen, and carcinoembryonic antigen in patients with adenocarcinoma of the uterine cervix, Obstet. Gynecol. 73, 661-668 (1989). 19 de Bruijn, H. W. A., van Beeck Calkoen-Carpay, T., Jager, S., Duk, J. M., Aalders, J. G., and Fleuren, G. J. The tumor marker CA-125 is a common constituent of normal cervical mucus, Amer. J. Obstet. Gynecol. 154, 1088-1091 (1986). 20. Fujii, S., Konishi, I., Nanbu, Y., Nonokagi, H., Kobayashi, F., Sagava, N., Mori, T., and Endo, K. Analysis of the levels of CA125, carcinoembryonic antigen and CA-19-9 in the cervical mucus for detection of cervical adenocarcinoma, Cancer 62, 541-547 (1988). 21. Morioka, H. Tumor-antigen (TA-4) of squamous cell carcinoma: Its tissue distribution and its relationship to serum TA-4 concentrations, Asia Oceania J. Obstet. Gynecol. 6, 91-97 (1980). 22. Kato, H., Morioka, H., Aramaki, H., Tamai, K., and Torigoe, T. Prognostic significance of the tumor antigen TA-4 in squamous cell carcinoma of the uterine cervix, Amer. J. Obstet. Gynecol. 145, 350-354 (183). 23. Dodd, J. K., Henry, R. J. W., Tyler, J. P. P., and Houghton, C. R. S. Cervical carcinoma: A comparison of four potential biochemical tumor markers, Gynecol. Oncol. 32, 248-252 (1989).
ONCOLOGY
37, 276-278 (1990)
Comparison between Squamous Cell Carcinoma-Associated Antigen and CA-125 in Patients with Carcinoma of the Cervix PENTTI LEHTOVIRTA,**’
LASSEVIINIKKA,t’$
AND OLAVI YLIKORKALA*
Departments of *Obstetrics and Gynecology and Whildren’s Hospital, Helsinki University Central Hospital, and Medical Research Institute Minerva, Helsinki, Finland Received September 6, 1989
carcinoma. In this work we compared the efficacy of
Serum levels of CA-125 and squamous cell carcinoma-associSCC antigen and CA-125 in detection of adenocarcinoma ated antigen (SCC) were measured in 30 patients with squamous and squamous cell carcinoma of the cervix. cell carcinoma and 12 patients with adenocarcinoma of the uterine cervix. SCC was elevated in 67% of patients with squamous cell PATIENTS AND METHODS carcinoma but in only 25% of patients with adenocarcinoma. In contrast, CA-125 was elevated in 75% of patients with adenoForty-two patients with biopsy-proven cervical cancer carcinoma but in only 26% of patients with squamous cell carwere studied (Table 1). Thirty patients had squamous cinoma. These data demonstrate the applicability of the measurement of CA-125 as a tumor marker for cervical cell carcinoma and twelve had adenocarcinoma. Before adenocarcinoma and confirm the value of the measurement of any treatment blood samples were drawn, and the sera SCC antigen in patients with cervical squamous cell carcinoma. of all patients were assayed for SCC antigen using a Moreover, we show that measurement of SCC antigen in ade- double-antibody radioimmunoassay (Abbott SCC-RIA, nocarcinoma and measurement of CA-125 in squamous cell car- Abbott Laboratories, Diagnostic Division, Abbott Park, cinoma are of insufficient clinical value. 0 I!390 Academic Press, Inc. North Chicago, IL). Levels above 2.0 rig/ml were con-
INTRODUCTION Squamous cell carcinoma-associated
antigen (SCC an-
tigen) is a subfraction of tumor antigen TA-4, which in 1977was purified from cervical squamous cell carcinoma [l]. It is a glycoprotein which is detected by immunohistochemical staining in all samples of malignant squamous cell neoplasms but only very rarely in normal glandular epithelium of the cervix [2]. SCC antigen is excreted into sera of patients with squamous cell carcinoma of the cervix, and its concentration in serum reflects the advance of the disease [3-51. It is well established that some lo-20% of cervical cancers are adenocarcinomas, and their proportion is increasing [6]. Yet almost nothing [5] is known of SCC antigen in cervical adenocarcinoma. Furthermore, the value of CA-125, a tumor marker used mainly for follow-up of epithelial ovarian carcinoma, has not been thoroughly assessed in the diagnosis of cervical ’ To whom reprint requests should be addressed: Departments of Obstetrics and Gynecology, Helsinki University Central Hospital, Haartmaninkatu 2, SF-00290 Helsinki, Finland.
sidered elevated, based on the data of our healthy controls (n = 20) and on those of the others [7]. In all but three patients with squamous cell cancer the levels of CA-125 were measured immunoradiometrically using commercial reagents (Abbott Laboratories, Wiesbaden, FRG). Levels above 35 IU/ml were considered elevated @I. Statistical analyses were carried out with the x2 test. RESULTS Twenty of thirty patients (67%) with cervical squamous cell carcinoma but only 3 of 12 patients (25%) with adenocarcinoma had elevated serum SCC antigen levels. This difference is statistically significant (P < 0.01). SCC antigen was raised in 50% of patients with stage I disease, as compared to 71 and to 82% of patients with stage II and III-IV disease (Fig. 1). Seven of twenty-seven patients (26%) with squamous cell carcinoma had elevated CA-125 levels, as compared to 9 of 12 patients (75%) with adenocarcinoma (Fig. 2). The difference is statistically significant (P < 0.01). Both markers were elevated in 22% and normal in 33% of
276 009%8258/90 $1.50 Copyright Q 1990 by Academic Press, Inc. All rights of reproductionin any form reserved.
CA-125 AND SCC LEVELS IN CERVICAL TABLE 1 Clinical Features of Patients with Carcinoma of the Cervix
Histology
Number of patients
Mean age in years (range)
30 12
64.0 (31-84) 64.7 (34-g5)
Squamous cell carcinoma Adenocarcinoma
1000
Clinical stage (FIGO) I
II
III-IV
12 7 6 4
11 2
patients with squamous cell carcinoma and in 25 and 25% of the patients with adenocarcinoma. Elevated SCC and normal CA-125 levels were found in 41% of patients with squamous cell carcinoma but in none of the patients with adenocarcinoma (P < 0.05). In contrast, elevated CA-125 and normal SCC levels were observed in 50% of patients with adenocarcinoma but only in 4% of patients with squamous cell carcinoma (P < 0.01) (Table
277
CANCER
I
0
“t*“., . l , . , ST
I
ST
II
ST III-IV
FIG. 2. Individual serum CA-125 levels in 27 patients with squamous cell carcinoma (0) and 12 patients with adenocarcinoma of the uterine cervix (0).
2).
DISCUSSION Cervical adenocarcinoma often grows inside the cervix and escapes detection by Pap smear [9]. Therefore, tumor markers detectable in the blood are needed to reveal the disease. Thus far, measurement of carcinoembryonic antigen (CEA) has been used for this purpose. Although preoperative plasma levels of CEA are more often elevated in patients with endocervical adenocarcinoma than in those with squamous cell carcinoma [lo-121, the lack
100~
0
0
8
:
l0
P :
10
-
b 5 I H
0
2.0 .--- ,i 4
1.0 0.5
8’ ----------
.0
0 l
I EL ST
j. ----- -mm----m-__
l
I
0%
0
of tumor specificity and tumor sensitivity of this antigen limits its diagnostic use [ 11,131.Also, CA-19-9 has shown to have inadequate sensitivity to justify use of this marker in patients with cervical cancer [13]. CA-125 is a differentiation antigen shared by Mtillerian derivates including the endocervix [14,15]. We show that CA-125 is elevated in 75% of patients with cervical adenocarcinoma, which means it might be applicable to the detection of this disease. Our result agrees well with earlier studies in which elevated levels of serum CA-125 were found in 57-83% of patients with primary cervical adenocarcinoma [ 16-181. Since the concentration of CA125 in cervical mucus is high in healthy subjects but decreased in patients with adenocarcinoma [19,20], its enhanced transfer from the endocervix into the circulation is a more likely mechanism for the raised level of blood CA-125 than its increased synthesis. Since SCC also exists in normal cervical squamous cells [21], it was expected that its transfer to blood may be enhanced during the malignant endocervical process. Our present data show, however, that this is not the
TABLE 2 Presence of Raised Levels of SCC and CA-125 in Patients with Epithelial and Adenomatous Carcinoma of the Cervix
0 0 ST
II
ST Ill-IV
FIG. 1. Individual serum SCC antigen levels in 30 patients with squamous cell carcinoma (0) and 12 patients with adenocarcinoma of the uterine cervix (0).
SCC/CA-125
Squamous cell carcinoma (%)
Adenocarcinoma (%)
Significance of the difference
Raised/raised Normal/normal Raised/normal Normal/raised
( 6127) 22 ( 9127) 33 (11/27) 41 ( l/27) 4
(3/12) 25 (3/12) 25
NS NS
W12~ 0
P < 0.05 P < 0.01
(6/12) 50
278
LEHTOVIRTA,
VIINIKKA,
case, and thus the measurement of SCC antigen is of no value in patients with cervical adenocarcinoma. This conclusion disagrees somewhat with the findings of Duk et al., who reported elevated SCC levels in 38% of patients with cervical adenocarcinoma, yet no relation to the stage of the disease was seen [18]. In accordance with a substantial amount of earlier data [3-5,7,22,23], SCC antigen is elevated in most patients with squamous cell carcinoma of the cervix in relation to the extent of the disease. The concentration of CA125 was elevated in only 26% of patients with squamous cell carcinoma, which is in full accord with the 20% reported by Senekjian et al. [7]. Thus, the measurement of CA-125 contributes little to the diagnosis of cervical squamous cell carcinoma. In conclusion, measurements of SCC antigen in squamous cell carcinoma and of CA-125 in adenocarcinoma of the cervix reveal about two-thirds of the patients. Their efficacy in revealing these diseases is thus of the same magnitude of many other tumor markers utilized in clinical practice. Their value may be limited in primary diagnosis, but most likely they are valuable in monitoring the course of these cancers. ACKNOWLEDGMENT The measurements of SCC antigen concentration were made in the Clinical Laboratory Medix (Espoo, Finland).
REFERENCES 1. Kato, H., and Torigoe, T. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma, Cancer 40, 1621-1628 (1977). 2. Flint, A., McCoy, J. P., Schade, W. J., Hotheinz, D. A., and Haines, H. G. Cervical carcinoma antigen: Distribution in neoplastic lesions of the uterine cervix and comparison to other tumor markers, Gynecol. Uncol. 30, 63-70 (1988). 3. Kato, H., Morioka, H., Tsutsui, H., Aramaki, S., and Torigoe, T. Value of tumor-antigen (TA-4) of squamous cell carcinoma in predicting the extent of cervical cancer, Cancer 50, 1294-1296 (1982). 4. Maruo, T., Shibata, K., Kimura, A., Hoshina, M., and Mochizuki, M. Tumor-associated antigen, TA-4, in the monitoring of the effects of therapy for squamous cell carcinoma of the uterine cervix, Cancer 56, 302-308 (1985). 5. Crombach, G., Wtirz, H., and Bolte, A. Bestimmung des SCCantigens in Serum von Patienten mit Zervixkarzinom, Geburrsh. Frauenheilk. 47, 439-445 (1987). 6. Brand, E., Berek, J. S., and Hacker, N. F. Controversies in the management of cervical adenocarcinoma, Obster. Gynecol. 71, 261-269 (1988). 7. Senekjian, E. K., Young. J. M., Weiser, P. A., Spencer, C. E., Magic, S. E., and Herbst, A. L. An evaluation of squamous cell carcinoma antigen in patients with cervical squamous cell carcinoma, Amer. J. Obstet. Gynecol. 157, 433-439 (1987). 8. Bast, R. C., Jr., Klug, T. L., St. John, E., Jenison, E., Niloff, J. M., Lazarus, H., Berkowitz, R. S., Leavitt, T., Griffith% T.,
AND YLIKORKALA Parker, L., Zurawski, V. R., Jr., and Knapp, R. C. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer, N. Engl. J. Med. 309, 883-887 (1983). 9. Korhonen, M. 0. Adenocarcinoma of the uterine cervix: An evaluation of the available diagnostic methods, Acta P&ho/. Microbial. Scnnd. A Suppl. 264, 3-51 (1978). 10. Rutanen, E.-M., Lindgren, J., Sipponen, P., Stenman, U.-H., Saksela, E., and Seppala, M. Carcinoembryonic antigen in malignant and nonmalignant gynecologic tumors. Circulating levels and tissue localization, Cancer 42, 581-590 (1978). 11. van Nagell, J. R., Jr., Donaldson, E. S., Gay, E. C., Rayburn, P., Powell, D. F., and Goldenberg, D. M. Carcinoembryonic antigen in carcinoma of the uterine cervix. 1. The prognostic value of serial plasma determinations, Cancer 42, 2428-2434 (1978). 12. van Nagell, J. R., Jr., Donaldson, E. S., Gay, E. C., Hudson, S., Sharkey, R. M., Primus, F. J., Powell, D. F., and Goldenberg, D. M. Carcinoembryonic antigen in carcinoma of the uterine cervix. 2. Tissue localization and correlation with plasma antigen concentration, Cancer 44, 944-948 (1979). 13. Schwartz, P. E., Chambers, S. K., Chambers, J. T., Gutmann, J., Katopodis, N., and Foemmel, R. Circulating tumor markers in the monitoring of gynecologic malignancies, Cancer 60, 353-361 (1987). 14. Kabawat, S. E., Bast, R. C., Jr., Bhan, A. K., Welch, W. R., Knapp, R. C., and Colvin, R. B. Tissue distribution of coelomicepithelium-related antigen recognized by the monoclonal antibody OC125, Int. J. Gynecol. Pathol. 2, 275-285 (1983). 15. Scharl, A., Crombach, G., Vierbuchen, M., Mtisch, H., and Bolte, A. CA-125 in normal tissues and carcinomas of the uterine cervix, endometrium and fallopian tube. I. Immunohistochemical detection, Arch. Gynecol. Obstet. 244, 103-112 (1989). 16. Niloff, J. M., Klug, T. L., Schaetzl, E., Zurawski, V. R., Knapp, R. C., and Bast, R. C., Jr. Elevation of serum CA-125 in carcinoma of the fallopian tube, endometrium, and endocervix, Amer. J. Obstet. Gynecol. 148, 1057-1058 (1984). 17. Crombach, G., Scharl, A., and Wtirz, H. CA-125 in normal tissues and carcinoma of the uterine cervix, endometrium and fallopian tube. II. Immunoradiometric determination in secretions, tissue extracts and serum, Arch. Gynecol. Obstet. 244, 113-122 (1989). 18. Duk, J. M., Aalders, J. D., Fleuren, G. J., Krans, M., and de Bruijn, H. W. A. Tumor markers CA-125, squamous cell carcinoma antigen, and carcinoembryonic antigen in patients with adenocarcinoma of the uterine cervix, Obstet. Gynecol. 73, 661-668 (1989). 19 de Bruijn, H. W. A., van Beeck Calkoen-Carpay, T., Jager, S., Duk, J. M., Aalders, J. G., and Fleuren, G. J. The tumor marker CA-125 is a common constituent of normal cervical mucus, Amer. J. Obstet. Gynecol. 154, 1088-1091 (1986). 20. Fujii, S., Konishi, I., Nanbu, Y., Nonokagi, H., Kobayashi, F., Sagava, N., Mori, T., and Endo, K. Analysis of the levels of CA125, carcinoembryonic antigen and CA-19-9 in the cervical mucus for detection of cervical adenocarcinoma, Cancer 62, 541-547 (1988). 21. Morioka, H. Tumor-antigen (TA-4) of squamous cell carcinoma: Its tissue distribution and its relationship to serum TA-4 concentrations, Asia Oceania J. Obstet. Gynecol. 6, 91-97 (1980). 22. Kato, H., Morioka, H., Aramaki, H., Tamai, K., and Torigoe, T. Prognostic significance of the tumor antigen TA-4 in squamous cell carcinoma of the uterine cervix, Amer. J. Obstet. Gynecol. 145, 350-354 (183). 23. Dodd, J. K., Henry, R. J. W., Tyler, J. P. P., and Houghton, C. R. S. Cervical carcinoma: A comparison of four potential biochemical tumor markers, Gynecol. Oncol. 32, 248-252 (1989).
