Placental alkaline phosphatase (PLAP)/PLAP-like alkaline phosphatase as tumour marker in relation to CA 125 and TPA for ovarian epithelial tumours

The significance of the PLAP (Placental alkaline phosphatase)/PLAP-like isozyme as tumour marker in relation to CA 125 and TPA for the monitoring of patients with malignant ovarian epithelial tumours was evaluated. Of all patients (n = 85), 40% had all three markers elevated. CA 125 being the most sensitive (60%), and the PLAP/PLAP-like isozyme and TPA both 40%. A tendency to certain tumour marker patterns of these three antigens in serum can be seen with regard to histopathology. Serous and anaplastic adenocarcinomas usually have all three markers moderately elevated, mucinous and mesonephric adenocarcinomas both have low incidences and low average levels of all three markers. Endometrioid and non-mucinous adenocarcinomas are often associated with high levels of the PLAP/PLAP-like isozyme and CA 125, while TPA shows moderate elevation. The PLAP/PLAP-like isozyme is positively correlated to tumour burden and the outcome of the disease. It may provide additional information on CA 125 in the monitoring of patients with ovarian cancer.     

组织多肽抗原在卵巢癌诊断及监测中的应用

目的评价组织多肽抗原（ＴＰＡ）在卵巢癌诊断和监测中的临床价值。方法应用放射免疫方法测定了２４例正常妇女、２７例妇科良性疾患及６０例卵巢癌患者的血清ＴＰＡ及ＣＡ１２５值并进行比较分析。结果ＴＰＡ在卵巢上皮性癌患者中的异常检出率为８２％,ＣＡ１２５为７０％,二者总的异常检出率为９２％。在绝大多数正常妇女和卵巢良性肿瘤患者中,ＣＡ１２５和ＴＰＡ在正常范围。作为卵巢癌相关标志物,ＴＰＡ与ＣＡ１２５具有相似敏感性。１９例动态观察结果显示,ＴＰＡ和ＣＡ１２５二者与病情转归是一致的。结论ＴＰＡ和ＣＡ１２５联合应用对卵巢癌的鉴别诊断及提高总的异常检出率具有价值。     

Serum levels of six tumor markers in patients with benign and malignant gynecological disease

Summary We studied the pretreatment serum levels of 6 tumor markers in gynecological patients with and without malignant disease. The tumor markers were carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), ferritin, Schwangerschaftsprotein 1 (SP₁), Schwangerschaftsprotein 3 (SP₃) and cancer antigen 125 (CA125). The results were as follows: (1) Serum CA125 and TPA levels were raised in 81% and 57% of patients with ovarian serous cystadenocarcinoma: CEA and SP₃, in 52% and 43% respectively of patients with ovarian mucinous cystadenocarcinoma; CA125, TPA and SP₃, in 76%, 48% and 48% respectively of patients with other ovarian malignancies; and TPA and SP₃, in 56% and 40% respectively of patients with endometrial carcinoma. (2) Serum levels of TPA, ferritin and CA125 were more often raised with advancing stages of malignant disease. (3) Serum TPA levels were elevated in 55% of patients with stage I endometrial carcinoma, and serum SP₃ levels were elevated in 35% of patients with a stage I malignant ovarian neoplasm and in 45% of patients with endometrial carcinoma. (4) One of the 6 tumor markers showed a raised level in 84% of patients with gynecologic malignancy as against 56% in those with benign gynecologic diseases.     

Monitoring human ovarian carcinoma with a combination of CA 125, CA 19-9, and carcinoembryonic antigen

CA 125 and CA 19-9 are antigenic determinants associated with human epithelial ovarian carcinomas. Murine monoclonal antibodies have been raised against these determinants, and immunoradiometric assays have been developed to monitor antigen levels in the serum of cancer patients. This study was undertaken to determine whether concomitant measurement of CA 125, CA 19-9, and carcinoembryonic antigen would provide a more precise correlation with tumor progression or regression than could be obtained with any single assay. Among 105 patients with surgically demonstrable epithelial ovarian carcinoma, serum CA 125 levels were elevated (greater than 35 U/ml) in 83%, CA 19-9, levels (greater than 37 U/ml) in 17%, and carcinoembryonic antigen levels (greater than or equal to 2.5 ng/ml) in 37%. Within individual samples, no correlation was found among values for the three markers, but patients with elevated CA 19-9 levels also had increased levels of CA 125. At least one of the three markers was elevated in 90% of the subjects. When 41 patients were monitored serially over 2 to 60 months, alterations in CA 125 levels correlated with disease progression or regression in 94% of instances, whereas alterations in CA 19-9 levels correlated in 33% and alterations in carcinoembryonic antigen levels in 25% of instances. Concomitant measurement of CA 125, CA 19-9, and carcinoembryonic antigen did not prove superior to measurement of CA 125 alone in the monitoring of patients with epithelial ovarian carcinoma.     

Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies

Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.     

The concomitant determination of different serum tumor markers in epithelial ovarian cancer: relevance for monitoring the response to chemotherapy and follow-up of patients.

The levels of CA125, CA19.9, CA15.3 CA72.4, and TATI were serially measured during and after chemotherapy in 43 patients with epithelial ovarian cancer having elevated concentrations of one or more of the antigens before initial surgery. The value of 35 U/ml was chosen as cutoff level of CA125 for the monitoring of disease. Changes in the serum levels of CA125, CA19.9, CA15.3, CA72.4, and TATI correlated with the clinical course of disease in 87.4% of 215, 76.3% of 80, 71.3% of 122, 76.0% of 167, and 48.5% of 101 instances, respectively. After the sixth course of monthly primary chemotherapy, elevated antigen levels were strong predictors of persistent disease, while normal antigen values were associated with both positive and negative second-look findings. It is worth noting that antigen levels above the cut-off limits before the third course, but still in the normal range after the sixth course, seemed to be predictive of positive second-look findings. Among patients with elevated antigen levels at diagnosis, clinical detection of neoplastic progression after treatment was stopped was preceded by an elevation of serum CA125 in 93.3% of 15 patients, of serum CA19.9 in 80.0% of 5 patients, of serum CA15.3 in 66.7% of 9 patients, of serum CA72.4 in 81.8% of 11 patients, and of serum TATI in 40% of 10 patients. In patients with positive CA125 assay at diagnosis, the concomitant evaluation of the other antigens did not seem to be of additional benefit for monitoring epithelial ovarian cancer. However, the measurement of the other tumor markers could represent an interesting biochemical tool for the management of patients with negative CA125 assay. In particular the evaluation of serum CA19.9 or CA72.4 could be very useful in the monitoring of patients with mucinous ovarian cancer, which often fails to express CA125 antigen.     

Serum concentrations of cancer antigen 125, placental alkaline phosphatase, cancer-associated serum antigen and free beta human chorionic gonadotrophin as prognostic markers for epithelial ovarian cancer

Objective To investigate the prognostic significance of elevated levels of cancer antigen 125 (CA125), placental alkaline phosphatase (PLAP), free β human chorionic gonadotrophin (hCG) and cancer-associated serum antigen (CASA) in women with primary epithelial ovarian carcinoma.
Design A two year follow up study of survival.
Setting A tertiary care gynaecological oncology unit.
Participants One hundred and eleven women with histologically confirmed epithelial ovarian cancer.
Main outcome measures Survival over a two year period.
Results Stage corrected log-rank χ² tests demonstrated a significant effect on survival for all four tumour markers (CA125   P = 0.0142  ; PLAP   P < 0.0001  ; CASA   P = 0.0098  ; hCG   P = 0.0002  ). This was confirmed when each variable was fitted together with disease stage in Cox proportional hazard models. When fitted as multiple variables in a Cox proportional hazard model, the addition of free β- hCG and CASA to disease stage, PLAP concentrations and CA125 levels did not demonstrate further prognostic value.
Conclusions Levels of all four markers correlate with survival in patients with epithelial ovarian cancer. The combination of PLAP and CA125 concentrations together with disease stage may be used to predict survival but the addition of hCG and CASA levels do not give additional prognostic information.     

Tumor markers CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen in patients with adenocarcinoma of the uterine cervix

Between 1978-1987, 439 patients with primary cervical carcinoma were admitted to our department. Seventy-seven patients (17.5%) had cervical adenocarcinoma and are reviewed in this retrospective study. Serial serum samples of these 77 patients were analyzed for cancer antigen 125 (CA 125), squamous cell carcinoma antigen, and carcinoembryonic antigen. Before treatment, only elevated serum CA 125 levels varied directly with the clinical stage of disease. In stages IB and II disease (International Federation of Gynecology and Obstetrics [FIGO]), the incidence of elevated serum CA 125 levels was highest in patients with adenosquamous tumor. Serum marker levels, measured 3 months after therapy, concurred with the treatment results. At that time, 17 of the 23 cases (74%) with at least one elevated serum marker level either had residual disease (N = 9) or developed recurrent disease during follow-up (N = 8), compared with six of the 40 cases (15%) with normal serum marker levels (P less than .001). Increasing serum marker levels during follow-up coincided with or preceded the clinical detection of recurrent disease. Tumor relapse, clinically located in the vaginal vault, occurred concomitant with a rise of at least one serum marker level in six of the seven cases (86%). All 15 patients with abdominal recurrence showed elevation of CA 125. In progressive disease, very high serum CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen levels were determined in patients with adenosquamous tumor, whereas patients with adenocarcinoma demonstrated only high CA 125 levels. We conclude that all three markers are important for monitoring patients with cervical adenocarcinoma.     

Multiple serum markers in patients with endometrial cancer

Serum levels of carcinoembryonic antigen (CEA), CA 125 and CA 15-3 were measured in 47 patients with endometrial cancer and 20 with endometrial hyperplasia. Before treatment elevated serum levels of CEA, CA 125 and CA 15-3 were found in 14, 43 and 32% of cancer patients, respectively. In the 20 patients with endometrial hyperplasia, CEA and CA 15-3 values were normal, while elevated CA-125 titers were detected in 1 case. There was an increasing incidence of abnormal levels of all markers in relation to a higher tumor stage (stage I: 36%; II: 66%; III: 100%). The percentage of positive marker values increased in case of deep myometrial infiltration (greater than M1) and/or poorer tumor differentiation (greater than G1). However, only percent increase in CA 15-3 positivity was significantly higher in more infiltrating (greater than M1, 7 vs. 65%, p less than 0.01) and less differentiated (greater than G1, 0 vs. 47%, p = 0.01) tumors. These findings suggest that CA 15-3 is in some way associated with the prognostic factors of the disease. All patients except 2 with no evidence of disease after surgery had normal serum marker values. Moreover, CA 125 and CA 15-3 levels reflected the clinical course of the disease during chemotherapy and seemed to be useful for monitoring response to treatment.     

Pretreatment serum levels of CA-125, carcinoembryonic antigen, tissue polypeptide antigen, and placental alkaline phosphatase, in patients with ovarian carcinoma, borderline tumors, or benign adnexal masses: relevance for differential diagnosis

Pretreatment serum levels of the antigens CA-125, tissue polypeptide Antigen (TPA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) were determined in samples from 295 women with adnexal masses. At laparotomy 48% of patients had epithelial ovarian carcinoma, 9% had tumors of low malignant potential, and 8% suffered from malignancies of other kinds. The sensitivity of CA-125 with 35 U/ml as the cutoff was 88% in women with ovarian carcinoma, but 74% among those with limited disease and 58% in borderline malignancy. Only 6 of 17 mucinous ovarian carcinomas were detected. Specificity was 83%. CEA was elevated above 5.0 micrograms/liter in 15 of 17 patients with mucinous ovarian cancer. TPA detected advanced stages of malignancy, but the sensitivity was low, 53%, in cases with limited disease. PLAP was elevated in 46% of ovarian carcinoma patients. For detecting malignancy overall, the use of a parallel combination of the CA-125 and CEA assays was more sensitive than use of CA-125 as a single marker. This test combination may be of value in the diagnosis of adnexal masses. The predictive value of a positive result was 90%, and that of a negative result, 76%.     

Pretreatment serum levels of CA-125, carcinoembryonic antigen, tissue polypeptide antigen, and placental alkaline phosphatase in patients with ovarian carcinoma: influence of histological type, grade of differentiation, and clinical stage of disease

Pretreatment serum levels of the tumor-associated antigens CA-125, tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) were analyzed in 142 patients with epithelial ovarian carcinoma, and related to clinical and histopathological parameters. In a linear multiple regression model CA-125 serum levels were profoundly influenced by the type of tumor, i.e., mucinous or nonmucinous. Clinical stage also had significant impact, whereas grade of differentiation did not, when the other two factors were taken into account. CEA levels were also dependent mainly on histological type. Mucinous tumor cases had high levels. Only clinical stage or tumor burden had a significant impact on TPA levels. PLAP levels were significantly influenced by histological type of tumor and by grade of differentiation but not by clinical stage. The dependence of CA-125 levels upon clinical stage was evident only in nonmucinous tumors. Furthermore, size of the primary tumor was not important for the CA-125 value, in contrast to FIGO stage. Thus CA-125 is primarily a sensitive indicator of disseminated disease in ovarian carcinoma patients. On the basis of the CA-125 level it was possible to predict the extent of disease with an overall accuracy of 55%. If TPA and CEA levels were also considered, the predictive accuracy was 63%.     

Intracystic evaluation of tumor markers in benign and malignant ovarian pathology

OBJECTIVE: To evaluate, in patients with benign and malignant ovarian cysts, serum samples and ovarian intracystic fluids for the presence of tumor markers such as CA 125, CA 15.3, tissue polypeptide antigen (TPA), CA 19.9 and the carcinoembryonic antigen (CEA). MATERIAL AND METHOD: We studied overall 64 patients with ovarian pathology. Sixteen patients were affected by functional cysts, 28 women by benign cystic tumors and 20 by cystoadenocarcinomas. RESULTS: Average serum levels of all but CA 15.3, TPA and CEA tumor markers of benign cystic ovarian tumors were higher than those of functional cysts. All but CA 19.9 mean intracystic fluid markers levels were more elevated in benign tumors than in functional cysts. In patients with malignant cystic tumors, all but CEA mean serum marker levels were higher than those of benign tumors; furthermore even all mean intracystic levels of markers were more elevated than those of benign tumors. CONCLUSION: This study confirmed the high positivity of tumor markers such as CA 125, CA 15.3, TPA, CA 19.9 and CEA in both the serum and intracystic fluid of patients with malignant epithelial ovarian tumors.     

A comparative evaluation of the ability of serum CA 125, CA 19-9, CA 15-3, CA 50, CA 72-4 and TATI assays in reflecting the course of disease in patients with ovarian carcinoma

The Authors compared the ability of serum CA 125, CA 19-9, CA 15-3, CA 50, CA 72-4 and Tumor-Associated Trypsin Inhibitor (TATI) assays in reflecting the disease course in a group of 27 patients with ovarian carcinoma. Before initial surgery, elevated levels of CA 125 (greater than 65 U/ml) were found in 27 patients, of CA 19-9 (greater than 40 U/ml) in 7, of CA 15-3 (greater than 32 U/ml) in 17, of CA 50 (greater than 20 U/ml) in 7, of CA 72-4 (greater than 3.8 U/ml) in 20, and of TATI (greater than 22 ng/ml) in 13. For each marker, only patients with elevated antigen levels at diagnosis were considered. CA 125, CA 19-9, CA 15-3, CA 50, CA 72-4 and TATI levels correlated with disease regression, stability or progression in 123/147 (83.7%), 24/34 (70.6%), 57/87 (65.5%), 26/38 (68.4%), 87/120 (72.5%), 33/75 (44.0%) instances respectively. Alterations in CA 125 levels correlated with disease status better than alterations in each other antigen levels. However serial measurement of the other tumor markers could be of help in the monitoring of patients with normal CA 125 values before initial surgery.     

Relationship of serum CA125 and lipid-associated sialic acid tumor-associated antigen levels to the disease status of patients with gynecologic malignancies

Serum samples obtained from 133 patients with gynecologic malignancies were assayed for two tumor-associated antigen markers: CA125, an ovarian marker, and lipid-associated sialic acid, a nonspecific marker. In the patient population, there were 77 papillary serous and 19 unspecified ovarian adenocarcinomas, and 24 miscellaneous ovarian carcinomas. Thirteen patients had nonovarian malignancies. Sixty-nine percent (74 of 108) of the patients with known disease had abnormal CA125 levels, whereas only 32% (20 of 63) had abnormal lipid-associated sialic acid levels. Changes in CA125 serum levels reflected the disease status of the patients for whom there were serial serum samples. Normal levels of CA125 corresponded to no evidence of disease in 100% (six of six) surgically evaluated patients and 75% (30 of 40) of clinically evaluated patients. Changes in CA125 levels from normal to abnormal corresponded to disease progression in 80% (12 of 15) of the patients. Decreases in CA125 levels from abnormal to normal corresponded to complete clinical response in 55% (11 of 20), and partial clinical response in 45% (nine of 20). No such correlations were available for lipid-associated sialic acid antigen levels. For tumors that express CA125 antigen, serum levels appear to be a good marker for the extent of malignant gynecologic disease. Levels of CA125 that rose from normal to abnormal were usually associated with recurrent disease.     

Measurement of CEA, TPA, neopterin, CA125, CA153 and CA199 in sera of pregnant women, umbilical cord blood and amniotic fluid

The following tumor markers were determined in body fluids associated with pregnancy: carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), neopterin, CA125, CA153 and CA199. CEA levels (cut-off 5.0 ng/ml) were not elevated during gestation, whereas TPA was above cut-off (85 U/l) in 98 out of 107 cases (range 40-408 U/l). TPA was significantly higher during the 3rd trimester of pregnancy than during the 1st and 2nd trimesters. 38.3% of CA125 measurements were slightly above the chosen cut-off of 35 U/ml, and the mean concentration was 33.5 +/- 16.2 U/ml. During delivery, 14 out of 21 values (67%) were elevated. Only 9.4% of CA153 values were elevated. CA199 and neopterin were also hardly ever above cut-off. In general, there was a wide scattering of individual values. With the exception of CA153 (neopterin not determined), high concentrations of CEA (maximum: 207 ng/ml), TPA (maximum: 1,565 U/ml), CA125 (maximum: 2,371 U/ml) and also CA199 (maximum: 1,533 U/ml) were found in amniotic fluid. The distribution in mixed cord blood was similar but with more moderate elevations and a lower incidence of levels above cut-off. Thus, none of these antigens is tumor specific. The term 'tumor-associated antigen' instead of 'tumor marker' is more appropriate. CEA, TPA, CA125 and CA199, but not CA153, are oncofetal antigens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical usefulness of sialyl SSEA-1 antigen as tumor marker for ovarian cancer as compared with CA125, CA19-9, TPA, IAP, CEA and ferritin

In order to determine the clinical significance of sialyl SSEA-1 antigen, we compared its usefulness as a tumor marker for ovarian cancer with simultaneously measured CA125, CA19-9, TPA, IAP, CEA and ferritin. The sialyl SSEA-1 antigen in serum was measured by radioimmunoassay with an "FH-6" Otsuka Kit. The immunohistochemical localization of sialyl SSEA-1 antigen in ovarian carcinoma tissues was determined by an immunoperoxidase method using FH-6 monoclonal antibody. Among fifty-one patients with ovarian cancer, the incidence of elevated serum levels was 54.9% with sialyl SSEA-1 antigen, 90.2% with CA125, 48.8% with CA19-9, 78.0% with TPA, 73.1% with IAP, 17.1% with CEA and 63.4% with ferritin. On the other hand, among the patients with uterine malignancies and gynecologic benign tumors, the incidence of elevated sialyl SSEA-1 antigen levels in serum was lower than that of other tumour markers. In the patients with ovarian cancer, the serum levels of sialyl SSEA-1 antigen increased in accordance with the advance of the clinical stage and were also correlated with the effect of therapy. In the examination of immunohistochemical localization of sialyl SSEA-1 antigen, a positive reaction occurred in 10 out of 30 ovarian carcinoma specimens. Intense staining appeared in the secretory materials, in the luminal surface of the glands, and in the cytoplasm of cells. Thus, sialyl SSEA-1 antigen appears to be a useful tumor marker for the diagnosis of ovarian cancer, especially when measured simultaneously with CA125, CA19-9, TPA, ferritin and IAP.     

Evaluation of serum CA 125 levels in the monitoring of ovarian cancer

Serum CA 125 levels were evaluated in 227 patients with ovarian cancer. CA 125 levels were elevated in 86% of the patients. All histologic types, including mucinous tumors, were associated with raised CA 125 levels. There was a positive correlation with tumor burden and an inverse correlation with degree of differentiation. In patients undergoing radical operation an elevated CA 125 level was a bad prognostic index. Serial CA 125 measurements were assessable in 112 patients undergoing chemotherapy. Rising or falling levels correlated with disease in 92% of the cases. The CA 125 level increased before clinical progression with a median lead time of 3 months. Only patients who showed objective response to chemotherapy had a decrease in antigen levels of greater than or equal to 30% 4 weeks after the first course of chemotherapy and a normalization of CA 125 levels 3 months after initiation of chemotherapy. Rising levels were always associated with progression. These data suggest that CA 125 may aid in early identification of nonresponders. However, a normal CA 125 level does not exclude the presence of disease.     

Combination assay of CA125, TPA, IAP, CEA, and ferritin in serum for ovarian cancer

The levels of CA125, TPA, IAP, CEA, and ferritin in the serum were measured simultaneously in 68 healthy nonpregnant females and 133 patients with various gynecological diseases, and were subjected to statistical discriminant analysis for the diagnosis of ovarian cancer. The usefulness and the limits for diagnosis of various gynecological diseases were investigated for each tumor marker. Also, the diagnostic usefulness of the stepwise discriminant analysis employing the values of these five tumor markers in the serum in cases of ovarian cancer was compared with that of CA125 measurements alone. Because the frequency of cases with an elevated serum CA125 level increased more specifically in the ovarian cancer group than those of other tumor makers in the serum, this parameter was considered to be more useful for the diagnosis of ovarian cancer than the levels of the other tumor markers. The frequencies of cases with the elevated serum CA125 levels, however, also increased in the groups of patients with endometriosis and at an early stage of normal pregnancy more than in the group of healthy nonpregnant females. In the ovarian cancer patients, the discriminant analysis employing the values of CA125 and four other tumor markers in sera was more useful for early diagnosis, differential diagnosis, early detection of recurrences, and the determination of complete remission after therapy than the measurement of the serum CA125 level alone.     

Experiments with tissue cultures from a human ovarian serous cystadenocarcinoma producing cancer antigen 125 (CA125), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA)

Summary The patient was a 57-year-old woman with ovarian serous cystadenocarcinoma in FIGO clinical stage IV. Cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) were immunohistochemically demonstrated in tumor cells, and the variations of serum CA125 and TPA levels reflected the clinical course. The tumor tissue obtained at exploratory laparotomy was minced with scissors, and transplanted subcutaneously into female nude mice for in vivo maintenance. The tumor cells from 5th generation nude mice were dispersed in Eagle's minimal essential medium supplemented with 10% fetal calf serum, and incubated in Falcon tissue culture dishes at 37°C in 5% CO₂ in air for in vitro maintenance. The results were as follows: Histopathologically the tumor transplanted into nude mice showed a cystadenocarcinoma, which closely resembled the original human tumor. Immunohistochemically CA125, TPA and CEA were demonstrated in the tumor transplanted into nude mice as well as in the original human tumor. From the growth curve in nude mice, the doubling time was estimated to be about 3.5 days. Serum TPA levels in nude mice were increased in proportion to the tumor growth after transplantation, but serum levels CA125 and CEA were normal. The concentrations of CA125 and TPA were increased in the conditioned media compared with the control media, although the elevated values were decreased with subsequent passages. CEA concentrations in the conditioned media were unchanged.     

Prediction of clinical course and recurrence of human ovarian cancer by several serum tumor markers

Measurement of serum tumor markers [lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBD), LDH-4, erythrocyte sedimentation rate (ESR), carcinoembryonic antigen (CEA), beta 2-microglobulin (beta 2M) and CA 125] was done before and after operation, and during the course of chemotherapy in 43 patients with advanced primary ovarian cancer. Pre-operative positive results for these serum tumor markers were 94.4% for CA 125, 62.2% for beta 2M, 54.8% for HBD, 51.3% for ESR and 46.5% for LDH, respectively. In a group of patients from whom most of the tumor mass had been removed, LDH, LDH-4 and HBD significantly declined after the operation, whereas in a group of patients with a large residual tumor after operation no significant change in any of the serum tumor markers examined was observed after operation. Except for CEA, all serum tumor markers in patients with complete response to chemotherapy significantly decreased after 3 courses of chemotherapy. From the analysis of predictive values for the recurrence of ovarian cancer, the most reliable tumor markers as a single marker appeared to be CA 125 and CEA, followed by ESR, LDH and LDH-4. However, in about 10% of cases, abnormal levels of CA 125 or CEA before treatment returned to the normal range after treatment and an increase in the other tumor markers was observed with a relapse of disease in the absence of an increase in CA 125 or CEA. These results suggest that in addition to such tumor markers as CA 125 or CEA, a combination assay of several tumor markers is necessary for monitoring of treatment of ovarian cancer.