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.     

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.     

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)     

A comparison of the usefulness of serum measurements of CA 125, CA 50 and TATI in patients with malignant and benign gynecological pathology

CA 125, CA 50 and Tumor Associated Trypsin Inhibitor (TATI) levels were assayed in blood samples drawn at diagnosis from 149 patients with malignant or benign gynecological pathology. CA 125 serum levels greater than 35 U/ml and 65 U/ml were respectively found in 34/38 (89.5%) and in 33/38 (86.8%) patients with ovarian carcinoma, in 17/61 (27.9%) and in 6/61 (9.8%) with benign ovarian pathology, in 6/30 (20.0%) and in 1/30 (3.3%) with cervical carcinoma, in 6/20 (30.0%) and in 6/20 (30.0%) with endometrial carcinoma. TATI serum levels greater than 22 ng/ml were observed in 17/38 (44.7%) patients with ovarian carcinoma, in 3/61 (4.9%) with benign ovarian pathology, in 1/30 (3.3%) with cervical carcinoma and in 3/20 (15.0%) with endometrial carcinoma. CA 50 serum levels greater than 20 U/ml were found in 11/38 (28.9%) patients with ovarian carcinoma, in 19/61 (31.1%) with benign ovarian pathology, in 7/30 (23.3%) with cervical carcinoma and in 6/20 (30%) with endometrial carcinoma. This study confirmed that CA 125 is the most reliable marker for ovarian carcinoma; however TATI could have a role in the diagnostic evaluation of adnexal masses, because of its very good specificity, CA 125 and CA 50, but not TATI, could be of some benefit in the management of endometrial and cervical carcinoma.     

Relation between serum levels of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) and their immunohistochemical identification in benign and malignant gynecological disease

Summary We studied immunohistochemical stains for TPA and CA125 in patients with benign and malignant gynecologic diseases. The results were as follows: (1) CA125 was not found in ovarian mucinous cystadenocarcinoma but was demonstrated immunohistochemically in 82% of ovarian serous cystadenocarcinomas and 83% of Krukenberg's tumors. (2) TPA was demonstrated in 65% of ovarian serous and 75% of ovarian mucinous cystadenocarcinomas, and in 58% of endometrial carcinomas. (3) TPA was found in all trophoblastic tumors examined, while CA125 was found in none. Eighty-three percent of patients with trophoblastic diseases had raised serum TPA levels. (4) When serum CA125 levels were raised, CA125 was demonstrated immunohistochemically in 71% of patients with ovarian serous cystadenocarcinomas, 67% of patients with Krukenberg's tumors and 100% of patients with tubal carcinomas. (5) Despite elevated serum levels, CA125 and TPA were not identified by immunohistochemistry in 64% cases of benign ovarian disease and in 80% of patients with uterine myomata. (6) It would seem that CA125 was more easily released from tumor cells than TPA.     

Assessment of biological variation and analytical imprecision of CA 125, CEA, and TPA in relation to monitoring of ovarian cancer.

OBJECTIVES: Changes in serial tumor marker results during monitoring of patients with ovarian cancer are due not only to deterioration or amelioration of the patient's condition, but also to preanalytical sources of variation (CPP), total random analytical error, and within-subject normal biological variation. The aim of the study was to assess (i) the analytical imprecision (CVA) and the average inherent intra- and interindividual biological variation (CVTI and CVG, respectively) for CA 125, CEA, and TPA in a group of healthy women; (ii) the significance of changes in serial results of each marker; and (iii) the index of individuality. METHODS: The study group consisted of 31 healthy women. Sixteen blood samples from each subject were collected in four series over a period of approximately 1 year. Data analysis was based on ANOVA. The index of individuality was calculated as ((CV2A + CV2TI)/CV2G)1/2 and the critical difference for a change between two consecutive concentrations as radical2xZx(CV2P + CV2A + CV2TI)1/2 (Z = 1.65 for unidirectional and 1.96 for bidirectional changes, P 相似文献   

CA 125 in the serum and tissue of patients with gynecological disease

Summary Serum levels of CA 125 were determined in 239 patients suffering from gynecological malignancies. The upper limit for normal was 35 U/ml. Raised levels were found in 82% of patients with primary ovarian carcinoma, and in 29% of those with benign ovarian tumors. The values from patients with ovarian carcinomas in partial or complete remission were compared with those from patients with progressive disease. The former group had elevated levels in 19% compared to 89% in the latter group. Fifty-four percent of the values in progressive cervical carcinoma and 41% of the levels in progressive endometrial carcinoma were greater than 35 U/ml. High CA 125 levels were found in the cytosol of placenta, ovarian carcinoma, cervical carcinoma, and in ascitic fluid; correlation with serum levels was satisfactory. Even though CA 125 is of limited specificity for ovarian cancer, serum levels are important for follow up care and for the early detection of recurrences.     

Clinical significance of statistical discrimination employing serum TA-4, TPA, and CEA levels in uterine cervical cancer

The serum levels of TA-4, TPA, and CEA were measured simultaneously in 52 patients with uterine cervical cancer and 99 healthy females. The findings were examined statistically by discriminant analysis method. The diagnostic usefulness of discriminant analysis employing the serum values for these three tumor markers was studied for uterine cervical cancer and compared with the diagnostic efficacy using each tumor marker alone. The following results were obtained: In the uterine cervical cancer patients, the frequencies of cases with the elevated serum levels were 55.8% for TA-4, 46.2% for TPA, and 36.5% for CEA. The functional formula, Z = 1.8395 log TA-4 + 3.5314 log TPA + 1.0130 log CEA-7.7352, was obtained by the stepwise discriminant analysis method. With the values obtained from this formula, 71.2% of patients with uterine cervical cancer were correctly classified in the uterine cervical cancer group. In the uterine cervical cancer patients, the values obtained from this formula increased according to the progression of the clinical stage and reflected the disappearance or persistence of tumor lesions after several therapies. From the above results, it was concluded that the discriminant analysis employing the serum values for three tumor markers was extremely useful in determining complete remission of uterine cervical cancers after several therapies, as well as for early diagnosis of the recurrences in uterine cervical cancer which were not detected by the cytologic smear examinations, compared with the measurement for each tumor marker alone. This discriminant analysis, however, was less effective for early diagnosis of uterine cervical cancer than the cervical cytologic smear test.     

Histochemical analysis of uterine cervical adenocarcinoma with reference to mucosubstances and distribution of CEA, CA125 and CA19-9

Epithelial mucin and immunohistochemical localization of carbohydrate antigens (CA125, CA19-9) in normal endocervical glands and adenocarcinoma of uterine cervix were examined histochemically. The materials were obtained from 33 surgical cases with adenocarcinoma and 9 control cases. Serial sections were examined by the following procedures: 1) Digestive PAS reaction, 2) High iron diamine-Alcian blue pH 2.5 staining, 3) Modification PAS and Thionin Schiff reaction to differentiate sialic acid, 4) Immuno-peroxidase method. Histologically, these adenocarcinomas were classified into four subtypes, endocervical, intestinal, endometrioid and serous adenocarcinoma. Endocervical adenocarcinomas were differentiated into the endocervical-intestinal group and serous-endometrioid group by mucin profiles and distribution of carbohydrate antigens. In endocervical and intestinal types, sialomucin was predominant, this mucin being characterized by O-acetylated sialic acid. Immunohistochemically, CA19-9, CA125 and CEA were localized in this group. The latter group of tumors were serous and endometrioid adenocarcinomas, characterized by surface coat type sulphomucin and non-acetylated sialic acid, but CA19-9 and CA125 were not detected in these cases. Adenoma malignum was classified in endocervical type adenocarcinoma.     

Clinical usefulness of the combination assay of CA 125, SLX, and CA 72-4 in patients with ovarian cancer

A serological diagnosis of ovarian carcinoma was performed using a combination assay consisting of three tumor markers. Cancer Antigen 125 (CA125), Sialyl Lex-i (SLX), and CA72-4. The results were compared with those for the individual tumor markers. Furthermore, the diagnostic accuracy of the combination assay was compared with that of image diagnosis in patients with stage I ovarian carcinoma. 1. The combination assay was positive in 90.3% of the patients with ovarian carcinoma. Classified according to the clinical staging system, the positive rate increased progressively with each stage, 77.6% in stage I, 92.0% in stage II, 98.5% in stage III, and 100.0% in stage IV. According to histological types, the positive rates were 93.8% in serous cystadenocarcinoma, 87.0% in mucinous cystadenocarcinoma, 88.9% in endometrioid carcinoma, and 85.7% in clear cell carcinoma. On the other hand, 6.9% of healthy persons and 38.6% of patients with various benign diseases were found to be false positive in this diagnosis. The high false-positive rate in the latter group is thought to result from the high false-positive rate of 73.5% and 57.1% for adenomyosis and pelvic endometriosis, respectively. 2. The accuracy of the image diagnosis and combination assay was compared in 58 cases with stage I ovarian carcinoma. Both procedures were positive in 38 cases (65.5%). Two cases (3.4%) were positive in image diagnosis but negative in the combination assay. Seven cases (12.1%) were negative in image diagnosis but positive in the combination assay.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tissue expression of CA 125 in benign and malignant lesions of ovary and fallopian tube: A comparison with CA 19-9 and CEA

Sections of formalin-fixed and paraffin-embedded tissue specimens of 11 normal ovaries and tubes, 13 tubo-ovarian abscesses, 3 tubal carcinomas, and 115 ovarian tumors were investigated by immunohistochemistry. CA 125 and CA 19-9 were demonstrated with monoclonal antibodies, CEA with polyclonal antibodies. The tissue expression was visualized by the avidin-biotin method. In the germinal epithelium of all ovaries no tumor marker was confirmed. In 4 out of 11 tubes the epithelium was CA 125 positive, in 2 out of 11 cases CA 19-9 positive. Nine out of 13 tubo-ovarian abscesses were CA 125 and 5 out of 13 were CA 19-9 positive in their epithelium. Elevated serum levels of these markers might be due to expression via the epithelial cell of the inflamed tube. All normal and inflammatory adnexal tissues were CEA negative. In serous tumors and undifferentiated carcinomas, CA 125 was most frequently confirmed (85 and 70%, respectively). All mucinous tumors were CA 125 negative. The most frequently confirmed tumor marker was CA 19-9 (77%). In endometrioid tumors, CEA was most frequent (44%). In 42% of the borderline tumors and carcinomas only one marker was demonstrated, in 7% none. Here, immunohistochemistry may indicate the most adequate marker. Tumor marker expression was markedly heterogenous: tumor areas with strong, weak, and no reaction were adjacent. The tumor markers revealed no specificity for malignancy or disease.     

Clinical usefulness of determination of CA 125 levels in the serum and menstrual blood

We measured CA 125 levels in sera and menstrual blood of subjects with a normal ovulatory cycle and in those with endometriosis. Serum CA 125 levels were higher in the latter, in each phase of the menstrual cycle. The CA 125 levels in patients with endometriosis, particularly those with adenomyosis, tend to be higher than in those with a normal ovulatory cycle. We propose that measurement of CA 125 in the menstrual blood may be able to help distinguishing adenomyosis from myoma uteri and may also help in assessing clinical endometriosis.     

Serum concentrations of CA 125, CA 15-3, CA 19-9 and CEA in normal pregnancy: a longitudinal study

Purpose  

Although cancer diagnosed during pregnancy is rare, the coexistence of pregnancy and malignancy becomes more common in view of prolongation of reproductive age. Therefore, it is important that the specificity of a tumor marker be evaluated during pregnancy to avoid misinterpretation in the follow-up of a pregnant cancer patient. The present study aims to investigate the serum concentrations of CA-125, CA 15-3, CA 19-9 and CEA in healthy pregnant women through gestation.     

术前测定血清CA125、CA199、CA724、CEA和GM-CSF在鉴别附件包块性质中的作用

探讨术前测定患者血清CA12 5、CA19 9、CA72 4、CEA和GM -CSF水平在鉴别附件包块良恶性质中的作用。方法 :74例附件包块患者术前 1周内采外周血 ,用固相免疫放射法测定各种肿瘤标志物浓度 ,并与术后组织学诊断比较。计算各标志物单独和联合应用诊断卵巢癌的相应诊断参数。结果 :( 1)CA12 5(临界值 70U/ml)鉴别卵巢肿瘤性质的敏感性和特异性分别为 85 71%和 82 61% ,CA19 9(临界值 30U/ml)分别为 4 2 86%和 73 33% ,CA72 4 (临界值 3 8U/ml)分别为 53 57%和 90 90 % ,CEA(临界值 5ng/ml)分别为 4 6 4 3%和 4 8 89% ;( 2 )联合应用肿瘤标志物 :CA12 5联合CA19 9的敏感性和特异性分别为 89 2 9%和 73 33% ;CA12 5联合CA72 4的敏感性和特异性分别为 89 2 9%和 75 56% ;CA12 5联合CEA的敏感性和特异性分别为 92 86%和 4 0 0 0 % ;( 3)如果去除 9例子宫内膜异位症 ,CA12 5、CA19 9、CA72 4和CEA的特异性分别增至 89 19% ,80 55% ,94 2 9%和4 7 2 2 %。结论 :此项研究应用的肿瘤标志物中以CA12 5最为敏感。将CA12 5临界值定为 70U/ml时诊断效果最佳。CA72 4的特异性最高 ,但诊断卵巢癌的敏感性低。CEA的诊断价值有限 ,GM -CSF则无价值。CA12 5与其他肿瘤标志物联合检测时诊断的特异性会部分丧失。?     

The effect of maternal age, parity, and fetal sex on the amniotic fluid and maternal serum levels of CA 125, CA 19.9, CA 15.3, and CEA

OBJECTIVE: To determine the effects of maternal age, parity and fetal sex on amniotic fluid (AF) and maternal serum (MS) levels of CA 125, CA 19.9, CA 15.3 and carcinoembryonic antigen (CEA). SUBJECTS AND SETTING: MS samples for CA 125, CA 19.9, CA 15.3 and CEA assay were obtained from 62 pregnant women at 16-20 weeks of gestation. AF was obtained from the same patients during genetic amniocentesis. METHODS: Radioimmuno assay to determine tumor marker concentrations. RESULTS: The following statistically significant differences were observed: (1) MS CA 19.9 and CA 15.3 values were elevated in the primigravida group. MS mean CA 19.9 value was also abnormally elevated. (2) MS mean CA 19.9 and CEA values and AF mean CA 19.9 value were elevated in the female fetus group. CONCLUSIONS: Parity and fetal sex were associated with AF and MS levels of some tumor markers. Therefore, to prevent misinterpretation of the tumor marker values during pregnancy further investigation is needed to find normal values for each trimester, paying particular attention to parity and fetal sex.     

Diagnostic value of the morphological ultrasound score system and the serum concentration of CA 125 in the diagnosis of malignant ovarian cancer

OBJECTIVES: The aim of this study was to estimate the diagnostic value of the morphological ultrasound score system and the serum concentration of CA 125 in the diagnosis of malignant ovarian masses. The aim was realized by the evaluation of the statistical coefficients like sensitivity, specificity, positive predictive value and negative predictive value in three groups tested by different methods (A--ultrasonography, B--serum concentration of CA 125, C--both methods). MATERIALS AND METHODS: We have analyzed 59 patients (17-77 years old)--mean 46.5 +/- 14.8 with ovarian malignant masses diagnosed in years 1999-2001. RESULTS: Merz morphological ultrasound score system revealed its sensitivity of 92.3%, specificity--87.9%, positive predictive value--85.7% and negative predictive value--93.7%. Statistical coefficients for serum Ca 125 marker concentration was not so attractive: sensitivity--57.7%, specificity--90.9%, positive predictive value--83.4% and negative predictive value--73.2%. Using both methods at the same time we obtained significantly different coefficients: sensitivity--96.2%, specificity--80.0%, positive predictive value--78.1% and negative predictive value--96.6%. CONCLUSIONS: Ultrasound assessment of ovarian morphology is very useful element in early detection of ovarian neoplasm. Serum CA 125 concentration assay is not a test verifying malignancy. Using both methods at the same time we increase its sensitivity and negative predictive value.     

Occurrence of CA 125 and CA 19-9 tumor-associated antigens in sera of patients with gynecologic, trophoblastic, and colorectal tumors

The present study was undertaken to test the parallel detectability of ovarian cancer antigen CA 125 and gastrointestinal cancer antigen CA 19-9 in the sera of patients with malignant ovarian tumors, benign ovarian tumors, endometrial cancers, cervical cancers, colorectal cancers, and trophoblastic tumors and in early 1st-trimester pregnant as well as in healthy nonpregnant controls. In all kinds of gynecologic and colorectal tumors raised concentrations of both antigens were found with the exception of malignant nonepithelial ovarian tumors where neither of the antigens showed positive reaction. The most positive cases were found in the group with epithelial ovarian cancers. Of the two antigens CA 125 was the more responsive. No positive cases were found with either of the antigens in nonpregnant healthy controls or in patients with benign ovarian tumors. The parallel determination of the two antigens gives us a better opportunity to recognize pelvic tumors and further may enable us to distinguish ovarian and colorectal tumors.     

Mechanism and clinical significance of elevated CA 125 levels in the sera of pregnant women

To clarify the mechanism of CA 125 elevation in maternal sera, serum levels of CA 125 and CA 19-9 were measured in 122 apparently healthy pregnant women (fifth to fortieth week of gestation) and 50 postpartum women (26 term deliveries and 24 second-trimester induced abortions). Serum levels of CA 125 showed an initial increase by the tenth week and then decreased to less than 35 U/ml, remaining below this level until delivery. However, within 1 hour after term delivery or second-trimester induced abortion, the CA 125 levels showed a second increase and decreased rapidly thereafter. In contrast, serum levels of CA 19-9 did not change significantly during these periods. Combined with our previous finding that the decidua contains abundant CA 125 but little CA 19-9, these results indicate that the elevated CA 125 levels in maternal sera originate from the decidual cells affected by chorionic invasion or the placental separation.