CA54/61 As a Marker for Epithelial Ovarian Cancer

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[CANCER RESEARCH 52, 1205-1209, March 1. 1992] CA54/61 as a Marker for Epithelial Ovarian Cancer Shiro Nozawa,1 Daisuke Aoki, Masazumi Yajima, Katsumi Tsukazaki, Toshibumi Kobayashi, Eizo Kimura, Yoshiteru Terashima, Noriyuki Inaba, Hiroyoshi Takamizawa, Yoshiyuki Negishi, Hisanao Ohkura, Hiroshi Sato, and Hiroshi Mochizuki Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160 [S. N., D. A., M. Y., K. T., T. K.]; Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-kit, Tokyo 105 [E. K., Y. T.J; Department of Obstetrics and Gynecology, School of Medicine, Chiba University, 1-8-1 Inohana, Chiba-shi, Chiba 280 (N. !.. H. T.J; Department of Obstetrics and Gynecology, Tokyo Medical College, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160 [Y. N.]; Department of Internal Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104 [H. O.J; and Laboratories for Bioscience, Mochida Pharmaceutical Co., Ltd., 1-1-1 Kamiya, Kita-ku, Tokyo 115 [H. S., H. M.J, Japan

ABSTRACT MATERIALS AND METHODS

Using a new one-step, double-determinant enzyme immunoassay, we Subjects. Sera were obtained from 348 healthy subjects, comprising performed quantitative measurements of a mucin-type glycoprotein anti 270 females and 78 males; from 351 patients with various noncancerous diseases, including 138 with ovarian benign tumors (including endo gen (CA54/61) that we recently detected in sera of ovarian carcinoma metriotic cyst), 27 with ovarian borderline tumors, 122 with uterine patients. When the cutoff value was set at 12 units/ml, at which a high myoma or adenomyosis, and 59 with benign disease of nongynecolog- diagnostic efficiency was demonstrated [or at 20 units/ml (mean + 3 SD ical organs: from 318 pregnant women; and from 43 umbilical cord of healthy females)], the positive rates of ovarian serous, mucinous, clear veins. Also 9 samples of amniotic fluid were taken. In 11 females, cell, and endometrioid carcinomas were 76% (or 63%), 63% (or 55%), samples were obtained at each stage of the menstrual cycle. Sera from 57% (or 52%), and 50% (or 38%), respectively. Even in mucinous 487 patients with various cancers, including 183 with ovarian cancers, cystadenocarcinoma, more than one-half of the cases were positive, 131 with uterine cervical cancers, 99 with uterine endometrial cancers, indicating the potential utility of the assay in the diagnosis of mucinous and 74 with cancers of nongynecological organs, were also assayed. A tumors. In sera from patients with benign ovarian tumors, only 9% (or group of comparisons of different tumor markers was also performed, 4%) of the cases were positive, indicating the quite high specificity of using a part of the samples mentioned above. In 138 patients with this test for ovarian carcinomas. To make a comparison between CA54/ benign gynecological disease and 163 patients with ovarian cancer, 61 and CA125, we set the cutoff level of CA125 at 110 units/ml, at which CA54/61 and CAI25 were measured simultaneously. In 85 and 27 value a high diagnostic efficiency was demonstrated [or at 35 units/ml patients with ovarian carcinoma, the simultaneous assay of CA54/61 (mean + 3 SD of healthy females)). When both CA54/61 and CA125 and CAI9-9 and that of CA54/61 and CEA were also performed, were assessed in sera from 36 patients with mucinous cystadenocarci respectively. Assay Systems. A new one-step, double-determinant enzyme immu noma, the positive rates of CA54/61 and CA125 were 64% (or 56%) and noassay system (MKS-15) containing monoclonal antibody MA54 as 36% (or 56%), respectively, suggesting that CA54/61 is of clinical value as a new tumor marker for ovarian cancers, including mucinous tumors. the immobilized antibody on beads and MA61 as the horseradish peroxidase-labeled antibody was used. To the test tube were added a 30 /iI serum sample, 250 //I of labeled antibody, and one bead coated with MA54. Incubation was carried out for 2 h at 37Â°C,followed by INTRODUCTION the enzyme reaction with 0.027% H2O2 and 3 mg/ml o-phenylenedi- amine in Macllvaine's buffer (48.5 mM citric acid-103 ITIMNa2HPO4, CAI25 (1, 2) is commonly used for the diagnosis of ovarian pH 5.0) as substrate and color developer, respectively. The absorbance epithelial carcinomas, but low CAI25 levels are frequently was measured at 492 nm. When a 50-ng sample of the standard antigen, encountered in cases of mucinous cystadenocarcinoma. Even obtained from the void fractions of culture supernatants of human lung markers such as CAI9-9 (3) and CEA2 (4, 5), which are often carcinoma cell line CI509 (6) by Ultrogel AcA 44 chromatography (IBF Bio-Technics, Villeneuve La Garenne, France), was defined as 1 unit effective for the diagnosis of various kinds of adenocarcinomas, of CA54/61, the measurable range of this assay was 1 to 200 units/ml. do not provide high positive rates in this type of ovarian tumor. The coefficients of variation of intraassay (10 simultaneous measure Since mucinous tumors, along with serous tumors (including ments of 4 sera with the same assay kit) ranged from 2.5 to 7.5%, and endometriotic cyst), are the most frequently encountered ovar the coefficient of variation of interassay (7 measurements of 4 sera with ian tumors, the development of markers useful for the diagnosis different assay kits) ranged from 4.4 to 6.5%. The recovery test was of mucinous tumors is an area of intense study. We have performed by the addition of 3 different concentrations of exogenous recently produced two monoclonal antibodies termed MA54 antigens to 3 sera, and the average of their recoveries was shown to be 91-102%. By serial dilutions of 3 sera, the concentration of CA54/61 and MA61, both of which recognize the carbohydrate moiety decreased linearly with increasing dilutions, and the values obtained in a high molecular weight mucin-type glycoprotein (6). Using were those expected. these two antibodies, we developed a sandwich enzyme immu CAI25 and CAI9-9 were measured with radioimmunoassay kits noassay for an antigen termed CAS4/61 and found that the (Centocor, Malvern, PA), and CEA was determined with an enzyme CA54/61 antigen was increased in the sera of patients with immunoassay kit (Roche, Basel, Switzerland). ovarian carcinomas including the mucinous type (6). In the present communication, using the improved assay system (6), RESULTS we report the results of the CA54/61 assay of sera from patients CA54/61 Values in Healthy Subjects and in Pregnancy. The with various ovarian lesions in a five-institution cooperative cutoff value of CA54/61 was set at two levels (Table 1). Since study and compare these results with those on CA125. the mean value and the standard deviation for healthy females were 5.1 and 4.9 units/ml, respectively, the first cutoff level was Received 9/18/91; accepted 12/17/91. The costs of publication of this article were defrayed in part by the payment set at 20 units/ml (mean + 3 SD of healthy females). The of page charges. This article must therefore be hereby marked advertisement in second cutoff level was set at 12 units/ml, at which a high accordance with 18 U.S.C. Section 1734 solely to indicate this fact. ' To whom requests for reprints should be addressed. diagnostic efficiency was obtained, as is shown later. Mean 2The abbreviation used is: CEA, carcinoembryonic antigen. values for healthy females in various age groups and those at 1205

Table l CA54/61 values for healthy and for pregnant subjects values included 3 [or 2] % with mucinous cystadenoma and 7, casesCutoff,Positive [or 4] % with benign endometriotic cyst. In borderline tumors, 12 20 11% [3 of 27] [or 7% (2 of 27)] of the patients had moderately units/mlMaleFemale<20yr20-29 units/mlNo.1511200103407%1.31.94.82.24.4002.2010.7077.8high values, and 2 of them had mucinous tumors. Among patients with ovarian carcinoma, positive rates were 76% [55 of 72] [or 63% (45 of 72)] for serous cystadenocarcinoma, 63% [24 of 38] [or 55% (21 of 38)] for mucinous cystadenocarci yr30-39 noma, 57% [13 of 23] [or 52% (12 of 23)] for clear cell yr40-49 carcinoma, 50% [8 of 16] [or 38% (6 of 16)] for endometrioid yr50-59 adenocarcinoma, 55% [6 of 11] for undifferentiated carcinoma, yr60-69 yr>70yrPregnancyUmbilical and 69% [9 of 13] [or 62% (8 of 13)] for metastatic carcinoma. Positive rates were less than 34% (or 23%), for patients with benign and malignant diseases aside from ovarian tumors. veinAmniotic Simultaneous Measurement of CAI 25 and CA54/61 in Pa fluidNo.7827021454545454524318439Mean3.45.15.95.75.24.74.75.44.88.12.341.7No.41926314215908%5.17.09.513.36.72.28.94.44.218.6088.9Cutoff,tients with Gynecological Tumors. Simultaneous measurements of both CAI 25 and CA54/61 were performed on sera from 138 Table 2 CA54/61 values for patients with various diseases patients with benign gynecological diseases and 163 patients Positive cases with ovarian carcinomas. Fig. 1 indicates the sensitivity (proportion of patients with Cutoff, 12 Cutoff, 20 units/ml units/ml positive values among patients with ovarian carcinoma), the specificity (proportion of patients with negative values among No. No. No. % patients with benign gynecological disease), the false-positive Ovary rate (proportion of patients with positive values among patients Benign ovarian tumor 138133038451227183723823161113101303271312355241386989.4010.05.315.68.311.167.276.463.256.550.054.569.280.0602040210545211266874.306.708.907.457.462.555.252.237.554.561.570.0 Serous cystadenoma with benign gynecological disease), and the diagnostic efficiency Mucinous cystadenoma (sensitivity x specificity) of CA54/61 and CAI25 at various Dermoid cyst cutoff values. The sensitivity of both markers fell as the cutoff Endometriotic cyst Others point was increased, with a complementary increase in the Ovarian borderline tumor specificity. When the cutoff values were set at mean + 3 SD of Ovarian carcinoma Serous cystadenocarcinoma healthy females (20 units/ml for CA54/61 and 35 units/ml for Mucinous cystadenocarcinoma CA125), the sensitivity was 56 and 80%, the specificity was 96 Clear cell carcinoma and 61%, and the diagnostic efficiency was 0.54 and 0.49 for Endometrioid adenocarcinoma Undifferentiated carcinoma CA54/61 and CAI25, respectively. In addition, another cutoff Metastatic carcinoma level of 12 units/ml for CA54/61 and 110 units/ml for CAI25 Other carcinoma was determined in order to compare both markers under the same situation where the sensitivity, specificity, false-positive Uterus Benign uterine tumor (myoma, 122 7.4 4.1 rate, and diagnostic efficiency of CA54/61 were almost equal adenomyosis) to those of CA125. CA125 and CA54/61 values and positive Uterine carcinoma Cervix 131 20 15.3 14 10.7 rates in sera of patients with gynecological benign and malig Epidermoid carcinoma 108 15 13.9 11 10.1 nant tumors were compared using the two of cutoff levels Adenocarcinoma 23 5 21.7 3 13.0 mentioned above. Endometrium 99 17 17.2 10 10.1 In benign gynecological diseases (Fig. 2), CAI25 was positive OtherorgansBenign in 40% [55 of 138] at the cutoff level of 35 units/ml [or 12% diseasesLung etc.)Stomach(pneumonia, (17 of 138) at the cutoff level of 110 units/ml], and especially etc.)Liver (ulcer, high positive rates, 64% [16 of 25] [or 24% (6 of 25)], were etc.)OthersCarcinomaLungStomachLiverPancreasColonBreastOthers1211201679159131382100130230016.79.10014.333.3022.223.1002100120020016.79.10014.322.20015.400(hepatitis,

various stages of the menstrual cycle demonstrated no remark able differences, and no definite trend was noted over the course of gestation in pregnant females. Forty-three umbilical blood samples yielded negative results; however, 78% (7 of 9) of the amniotic fluid samples gave higher values than the cutoff level 20 26 ES 110 150 200 of 20 units/ml, registering a relatively high mean value of 41.7 cutoff value (unit/ml) cutoff value (unit/ml) units/ml. Fig. 1. Comparison of the diagnostic efficiency of CA54/61 and CA125. O, CA54/61 Values in Patients with Various Diseases. In patients sensitivity (S. I'., proportion of patients with positive values among those with with benign ovarian tumors [Table 2], the positive rate was 9% ovarian cancer); â€¢¿,specificity(S. P., proportion of patients with negative values among those with benign gynecological disease); A, false-positive rate (F. P., [13 of 138] at the cutoff level of 12 units/ml, [or 4% (6 of 138) proportion of patients with positive values among those with benign gynecological at the cutoff level of 20 units/ml], and the patients with positive disease); D, diagnostic efficiency (D. E., sensitivity x specificity). 1206

PositivMOU lunit/ml)imÂ» 125 54/61(unit/milin Rale20 CA54/61 and CEA was -0.04. Thus, no correlation was found ml0% Um9% ioa> IDO. 000 10000PositivI2Uml0% Uml0% between CA54/61 and either CAI9-9 or CEA. cystadeooma (0)5% (1)14% (11)Mutinous (0)14% (0)10%

..1 'â€¢T-,-tâ€”"1 cystMtencxni(21)Dermoid DISCUSSION (1)7% (3)32% (3)7% (2)0%

1râ€¢ The clinical validity of tumor markers is evaluated by their cyst (2)24% (9)64% (28)EndometrioÂ« (2)24% (0)12% sensitivity, specificity, and diagnostic efficiency. These values,

-vr"â€¢ -â€”â€¢W"-I***CA however, change according to the cutoff value; thus it is impor cyst (6)17% (16)46% (25)M/oma (6)7% (3)2% tant how the cutoff value is determined. The cutoff value should 1-I-â€¢ AdenomnÂ»rs be set according to the clinical purpose. (7)8% (19)58% (41)Others (3)8% (1)0% In this study, CA54/61 was characterized as a new ovarian -*(cases)Serous tumor marker demonstrating a low false-positive rate for (12)Total (1)12.3%(7)39.9% (1)10.9% (0)4.3% healthy females (1.9%), healthy males (1.3%), and benign dis â€¢¿nÂ»KIO-,^,,-^1^â€¢ (17)Rate35(55)Ã‡A (138)10-,-.(H-^ (15)e (6) eases (4.4%) and a high positive rate in ovarian carcinomas (57%) at the first cutoff level, which was calculated as the mean Fig. 2. Simultaneous measurement of CA54/61 and CAI25 in patients with + 3 SD of healthy females. Currently, CAI25 is being used benign gynecological tumors. widely as an ovarian tumor marker. It is well known, however, that CAI25 measurements give a high false-positive rate for benign diseases, particularly endometriosis, at the cutoff level demonstrated in patients with benign endometriotic cyst. On of 35 units/ml which equals the mean + 3 SD (8). Thus other the other hand, CA54/61 was positive in only 11% [15 of 138] cutoff levels have been proposed; for example, a cutoff level of even at the cutoff level of 12 units/ml [or 4% (6 of 138) at the 65 units/ml should be used to discriminate between malignant cutoff level of 20 units/ml] of benign gynecological diseases, and benign diseases (1), or one of 50 units/ml is occasionally showing only 3 [or 2] cases in 21 cases of mucinous cystadenoma used under consideration for assessment of the fluctuation of and 6 [or 3] cases in 25 cases of benign endometriotic cyst as the values during the menstrual cycle of healthy females (9). positives. For comparison of the usefulness as an ovarian tumor marker In malignant ovarian tumors (Fig. 3), CAI25 was positive in between CA54/61 and CAI25, simultaneous measurements 80% [131 of 163] at the cutoff level of 35 units/ml [or 64% were performed. The usefulness of a tumor marker is usually (105 of 163) at the cutoff level of 110 units/ml], and a high defined as the degree to which the marker discriminates between positive rate, 75-100% [or 50-90%), was demonstrated in the malignant and benign diseases. This ability can be minier patients with every histological type except mucinous cystad- alized as the diagnostic efficiency which is calculated as the enocarcinoma, which patients registered 56% [20 of 36] [or product of sensitivity x specificity. Since the maximum diag 36% (13 of 36)]. In mucinous cystadenocarcinomas, the positive nostic efficiency spread over a wide range, as shown in Fig. 1, rate of CA54/61 was higher, being 64% at the cutoff level of to the diagnostic efficiency was attached one more condition 12 units/ml [or 56% at the cutoff level of 20 units/ml], although where the false-positive rates in gynecological diseases were CA54/61 showed an overall 66% [108 of 163] positive rate in suppressed at about 10%. The second cutoff levels were thus total ovarian carcinomas at the cutoff level of 12 units/ml [or determined at 12 units/ml for CA54/61 and 110 units/ml for 56% (92 of 163) at the cutoff level of 20 units/ml]. CA125, so that abilities of CA125 and CA54/61 for picking up As shown in Table 3, 2 x 2 table analyses were performed the ovarian carcinomas were almost identical. Therefore, at according to a paired x2 test (7) in order to compare statistically these second cutoff levels, there was only a slight difference in the validity of CAI 25 and CA54/61 as ovarian tumor markers. positive rate for ovarian carcinomas (66% for CA54/61 and The sensitivity for mucinous cystadenocarcinoma in addition 65% for CAI25) and in false-positive rate for gynecological to that for total ovarian carcinomas and the specificity for benign diseases (11% for CA54/61 and 12% for CAI25), as benign diseases were calculated and are shown in Table 3. These was shown in Fig. 1. However, regarding these data, special 2x2 tables indicate that at the first cutoff level, CAI25 was attention should be paid to the fact that mucinous cystadeno- significantly superior to CA54/61 for ovarian carcinoma in sensitivity (P < 0.001) but was inferior in specificity (P < PositiveRate' 125 (unit/ml) ml)hâ€¢ 54/61 (unit Ratei:U : uâ€¢¿":79% 0.001). Meanwhile, at the second cutoff level, CA54/61 was Uml86% Iâ€¢â€¢iâ€”rrr-v"-10000 1000 100 ml77% â€¢¿64%

'â€¢ ' â€¢¿â€¢â€¢¿'-frfi*"n(cases)Serous â€¢¿IT-!â€¢â€¢â€¢â€¢â€¢â€”¿ almost equal to CAI25 in sensitivity for ovarian carcinomas (52)36% (57)56% (66)Mucinous(36)Clear (51)64% (42)56% and in false-positive rate for benign diseases (specificity) and .-Ml"r "I-K-....-.â€¢ -. -i â€¢¿ was significantly superior to CAI25 in sensitivity for mucinous (13)50% (20)89% (23)50% (20)50% cystadenocarcinoma (P < 0.01). -p...VTtK^r-.+^e*'-Â»P cell (9)50% (16)75% (18)ErxJo (9)58% (9)42% The results of simultaneous measurements of CA54/61 and metnoid (6)90% (9)100% CAI25 in 163 patients with ovarian epithelial carcinoma are (12)LI'W.'W" (7)60% (5)60% plotted in Fig. 4. The correlation coefficient between CA54/61 tiated -â€”Â¿r|-tr" and CAI25 was as low as 0.52. All of the seven sera which were (9)63% (10)88% (10)Metastat'C (6)63% (6)50% .... positive for CA54/61 and negative for CAI25 at the cutoff (5)85% (7)92% (8)Others(13)(163)CA (5)54% (4)46% levels, determined as mean + 3 SD, were obtained from muci ..W**--Â«- nous cystadenocarcinoma cases. (11)64.4%(12)80.4% (7)66.3% (6)56.4% Correlation between CA54/61 and CAI 9-9 or CEA. The cor .Positive relation coefficient between CA54/61 and CAI9-9 values, (105)35 (131)CA (108).<.;) (92) which was calculated from the serum value of each tumor Fig. 3. Simultaneous measurement of CA54/61 and CAI25 in various histo marker converted to logarithm, was -0.01; and that between logical types of ovarian carcinomas. 1207

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Downloaded from cancerres.aacrjournals.org on September 27, 2021. © 1992 American Association for Cancer Research. CA54/61 AS MARKER FOR EPITHELIAL OVARIAN CANCER ooooo-10000-1000-110 different antigenic determinants are presumably present on this molecule, it may be possible to establish other assay systems

1 utilizing antibodies that recognize different antigenic determi 1 1 Â»x nants on the CA54/61 molecule. Since mucin-related markers 1t such as CA72-4 have also been reported (10), comparisons 0OÃ•O, 0A Â° AÂ°0 with these tumor markers will require attention in the near Â°O Â° 0 future. !0 B We have demonstrated that CA54/61 in itself is a useful o iâ€¢ AO o OL tumor marker for ovarian cancers, characterized by low positive AwA?nÃ¼ O O * 0 rates for other carcinomas and benign diseases and the high 1^iD xÃŒ^^D positive rate for ovarian cancers including mucinous cystaden i â€¢¿ "iDÃŒODD â€¢¿A ocarcinoma. It has been documented, on the other hand, that o ftâ€¢¿Â° CAI25 is a useful ovarian tumor marker because of the very *Ã* Ã• D high positive rate for ovarian cancers, even though it also shows 100-35Â¡I * Â°A0 high false-positive rates for benign diseases, especially for endo-

Â¡Â¿2. AA^A â€¢¿^.0 metriosis (8), when the cutoff value is set at the mean + 3 SD (35 units/ml) of healthy females. Taking all of these data together, we foresee that CA54/61 will be of clinical value as a ^ \ o â€¢¿!o1012 new tumor marker to supplement some of the disadvantages of ''oo0010000CA 100 1000 CAI25 in view of its considerably low false-positive rate and 54/61 (unit/ml) favorable sensitivity for mucinous cystadenocarcinoma.

Fig. 4. Correlation between CA125 and CA54/61 in patients with ovarian carcinomas. O, serous cystadenocarcinoma (66 cases); â€¢¿,mucinouscystadenocar- ACKNOWLEDGMENTS cinoma (36 cases); A, clear cell carcinoma (18 cases); A, endometrioid adenocarcinoma (12 cases); O, undifTerentiated carcinoma (10 cases); â€¢¿.metastaticcarci We are indebted to M. Sakayori at the Laboratory of Gynecologic noma (8 cases); x, others (13 cases). Pathology, School of Medicine, Keio University, and K. Nagoya, S. Furusako, and T. Kudo at Mochida Pharmaceutical Co., Ltd., for their carcinomas demonstrated a much higher positive rate for skillful technical assistance. CA54/61 (64%) than for CAI25 (36%). These points were confirmed by the results of statistical 2 x REFERENCES 2 table analyses. At the first cutoff level, the positive rate of 1. Bast, R. C., Jr., Klug, T. L., John, E. S., Jenison, E., Niloff, J. M., Lazarus, CAI25 for ovarian carcinomas (sensitivity) was superior to that H., Berkowitz, R. S., Leavitt, T., Griffiths, C. T., Parker, L., Zurawski, V. of CA54/61 (P < 0.001), but CAI25 gave a much higher false- R., Jr., and Knapp, R. C. A radioimmunoassay using a monoclonal antibody positive rate than CA54/61. At the second cutoff level, on the to monitor the course of epithelial ovarian cancer. N. Engl. J. Med., 309: 883-887, 1983. other hand, positive rates of CA54/61 for ovarian cancers and 2. Klug, T. L., Bast, R. C., Jr., Niloff, J. M., Knapp, R. C., and Zurawski, V. gynecological benign diseases (sensitivity and false-positive R., Jr. Monoclonal antibody immuno-radiometric assay for antigenic deter minant (CA12S) associated with human epithelial ovarian carcinomas. Can rate, respectively) were the same as those of CAI25; but for cer Res., 44: 1048-1053, 1984. mucinous cystadenocarcinoma, CA54/61 was distinctly statis 3. Canney, P. A., Wilkinson, P. M., James, R. D., and Moore, M. CA19-9 as tically superior to CAI25 (P < 0.01). a marker of ovarian cancer: alone and in comparison with CAI25. Br. J. Cancer, 52:131-133, 1985. Another point from these 2x2 table analyses should be 4. Rutanen, E. M., Lindgeren, J., Sipponen, P., Stenman, U. 11, Saksela, \ ., noticed; i.e., at the second cutoff value, there were no false- and Seppala, M. Carcinoembryonic antigen in malignant and nonmalignant positives in the group defined as positive for both CA54/61 and gynecologic tumors. Cancer (Phila.), 42: 581-590, 1978. 5. Van Nagell, J. R., Jr., Donaldson, E. S., Gay, E. C., Sharkey, R. M., Rayburn, CAI25, indicating that both positive cases were all ovarian P. R., and Goldenberg, D. M. Carcinoembryonic antigen in ovarian epithelial carcinomas and these cases occupied 53% of ovarian cancer cystadenocarcinomas. The prognostic value of tumor and serial plasma cases assessed in this study. These data strongly suggest that a determinants. Cancer (Phila.), 41: 2335-2340, 1978. 6. Nozawa, S., Yajima, M., Kojima, K., lizuka, R., Mochizuki, II., Sugawara, combination assay of CA54/61 and CAI25 at the second cutoff T., Iwamori, M., and Nagai, Y. Tumor associated mucin-type glycoprotein level is quite useful for reliable diagnosis of ovarian carcinomas. (CA54/61) defined by two monoclonal antibodies (MA54 and MA61) in Also the combination assay of CA54/61 and another marker ovarian cancers. Cancer Res., 49:493-498, 1989. 7. McNemar, Q. Note in sampling error of the difference between correlated such as CA125, CA19-9, or CEA will be useful for the screening proportion on percentage. Psychometrika, 12:153-157, 1947. by the reason of their low correlation coefficients. 8. Pittaway, D. E., and Payez, J. A. The use of CAI25 in the diagnosis and management of endometriosis. FÃ©rtil.Steril., 46: 790-795, 1986. CA54/61 is a carbohydrate antigen recognized by two mono 9. Sakamoto, S., Kawana, II., Shimizu, K., Ishihara, T., Ueda, K., Usman, S. clonal antibodies, MAS4 and MA61. The antigenic determi N., Uchida, S., Kawagoe, K., Kihara, K., and Kubo, H. Detection of CA-125 nants reactive with these two antibodies differ; MA54 was found antigen (non-mucinous ovarian cancer antigen) in serum of patients with gynecologycal malignancies (in Japanese). Acta Obstet. Gynecol. Jpn., .16: to recognize a mucin-type carbohydrate chain containing a 1261-1262, 1984. terminal sialic acid (NeuAc a 2-6 galactose), whereas MA61 10. Murano, R., Kuroki, M., Wunderlich, D., Poole, D. C., Colcher, D., Thor, was shown to recognize a mucin-type carbohydrate chain with A., Grener, J. W., Simpson, J. F., Molinolo, A., Noguchi, P., and Schlom, J. Generation and characterization of B72.3 second generation monoclonal out sialic acid (6). CA54/61, therefore, represents a molecule antibodies reactive with the tumor-associated glycoprotein 72 antigen. Cancer carrying these two antigenic determinants. Because many other Res., 48: 4588-4596, 1988.

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~~Shiro Nozawa, Daisuke Aoki, Masazumi Yajima, et al.~~

~~Cancer Res 1992;52:1205-1209.~~

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