Clinical usefulness of serum sialyl SSEA-1 antigen levels in patients with epithelial ovarian cancer. Comparative effectiveness of sialyl SSEA-1 and CA 125

The serum levels of sialyl SSEA-1 antigen, a type 2 chain carbohydrate antigen detected using the monoclonal antibody FH-6, were elevated in 47.2% of patients with epithelial ovarian cancer, with the percent positivity increasing with the clinical stage. Of the histological type, it is interesting to note the relatively high sensitivity in patients with mucinous adenocarcinoma and clear cell carcinoma in contrast with the CA 125 antigen levels. Although the percentage of patients with ovarian cancer who had elevated sialyl SSEA-1 antigen levels is lower than that observed with elevated CA 125 antigen levels, the false-positive rate is significantly low in the sialyl SSEA-1 test. Serial sialyl SSEA-1 antigen levels obtained during follow-up were strong predictors of clinical outcome. The combined determination possible with sialyl SSEA-1 and CA 125 did not markedly increase the detection rate because of the overlap in the positivity. However, increased levels of both serum sialyl SSEA-1 antigen and CA 125 antigen indicated the presence of malignancies in pregnant women associated with ovarian tumors.     

The clinical usefulness of the measurement of serum sialyl SSEA-1 antigen levels in patients with gynecologic diseases: as respects the comparative effectiveness of sialyl SSEA-1 and CA125

Increased concentrations of serum Sialyl SSEA-1 antigen, which belongs to type 2 chain carbohydrate antigens and is defined by a new monoclonal antibody FH-6, were observed in 47.2% of patients with ovarian cancer. The Sialyl SSEA-1 test may not be of use in detecting ovarian cancer in the early stages, because the positivity gradually increased with the clinical stages. However, the measurement of the Sialyl SSEA-1 concentrations was a useful tool to use in making a prognosis. The sialyl SSEA-1 and CA125 combination test was not useful in increasing sensitivity because of overlapping of the positivity. Increases in both serum Sialyl SSEA-1 and CA125 indicated the presence of malignancies associated with ovarian tumors in pregnant women. On the other hand, the Sialyl SSEA-1 test showed significantly low false positivity for non-neoplastic diseases except endometriosis.     

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.     

Clinical value of sialyl SSEA-1 antigen in patients with ovarian cancer

The efficacy of sialyl SSEA-1 antigen (SLX), a tumor-associated carbohydrate antigen, as a test for gynecological cancer was investigated. The test was found to be positive in 64.5% of all patients with ovarian cancers; this rate is lower than that obtained with CA 125. On the other hand, relatively few false-positive results were observed. Tests were false-positive in 25.0% of patients with endometrial cysts; 25.0% of women in the first trimester of pregnancy and 0.0% of menstruating woman had false-positive results. These percentages were lower than those for CA 125. It is concluded that SLX is a tumor marker with inferior sensitivity and high specificity, compared with CA 125. Since positive tests with SLX in patients with ovarian cancer mostly overlapped the positive tests for CA 125, the usefulness of a combination assay was considered to be low. The SLX test was positive in 18.6 and 25.0% of patients with cervical cancer and endometrial cancer, respectively, and it was concluded that SLX is useless as a serum tumor marker for uterine cancer.     

人附睾分泌蛋白4联合CA125在卵巢恶性肿瘤与子宫内膜异位症鉴别诊断中的价值

目的 探讨血清人附睾分泌蛋白4(HE4)联合CA125水平检测在卵巢恶性肿瘤与子宫内膜异位症鉴别诊断中的价值.方法 采用酶联免疫吸附试验(ELISA)检测卵巢子宫内膜异位囊肿(内异症组)46例、卵巢上皮性癌(卵巢癌组)36例、卵巢非内膜异位良性肿瘤(良性肿瘤组)60例和健康妇女(对照组)50例血清中HE4和CA125水平,结果以中位数表示.血清HFA和CA125正常值分别为0～150 pmo/L和0～35 kU/L,单独或联合检测时,其中任一指标高于正常上限即定为阳性.通过制作受试者工作特征(ROC)曲线,以曲线下面积(AUC)反映诊断的准确性;以Mann-Whitney U 检验及相关性分析探讨两项指标单独或联合检测用于诊断卵巢内异症囊肿的价值.结果 (1)HE4水平:内异症、对照、良性肿瘤组妇女血清HE4水平分别为52.4、51.0、50.0 pmoL/L,3组比较,差异无统计学意义(P>0.05),卵巢癌组患者HE4水平为507.5 pmoL/L,与其他3组分别比较,差异均有统计学意义(P<0.05).(2)CA125水平:卵巢癌、内异症、良性肿瘤及对照组妇女血清CA125水平分别为743.0、84.9、15.4、11.5 kU/L,卵巢癌组与其他3组比较,差异均有统计学意义(P<0.05).(3)单项榆测结果:卵巢癌组以内异症组为参照时,HE4和CA125笛单项检测的AUC分别0.933和0.821,其特异度为95%时的敏感度分别为79.6%和49.0%;内异症组以对照组为参照时的AUC为0.453;以良性肿瘤组为参照时的AUC为0.496.(4)联合检测结果:卵巢癌组以内异症组为参照时,HE4联合CA125检测的AUC为0.936,其特异度为95%时的敏感度为81.0%.结论 HE4水平可作为卵巢内异症囊肿的鉴别诊断依据之一,HE4联合CA125水平检测能有效鉴别卵巢内异症囊肿和卵巢恶性肿瘤.     

Meigs' syndrome with elevated serum cancer antigen 125 levels in a case of ovarian sclerosing stromal tumor

ObjectiveMeigs’ syndrome presenting as an ovarian tumor with elevated serum cancer antigen 125 (CA 125) levels is unusual. Only 37 cases have been reported, including three cases of ovarian sclerosing stromal tumor (SCT). Many reports have suggested that the presence of ascites is the major factor inducing mesothelial expression of CA 125.Case ReportAn 18-year-old woman presented with massive ascites, elevated serum CA 125 levels, and radiographic evidence of ovarian tumor. The histological and immunohistochemical examinations revealed a benign SCT.ConclusionSCT is a benign ovarian tumor and complete excision is curative. We also review all 37 cases and discuss possible mechanisms of Meigs’ syndrome and elevated serum CA 125 level.     

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.     

Clinical evaluations of the tumor marker sialyl SSEA-1 antigen for clinical gynecological disease

Sialyl SSEA-1 antigen (SLX) is a highly specific tumor marker composed of sugar chain antigens that have Lewis X at their terminals and bind to sialic acid. This antigen is rarely detected in normal tissues, and is present in adenocarcinoma and fetal tissues. We studied the clinical usefulness of SLX in gynecological patients and obtained the following results. (1) The antigen was frequently positive in patients with ovarian cancer with a mean of 89.5 +/- 48.3 U/ml (72.8%, 8/11) and in those with endometriosis with a mean of 39.8 +/- 10.3 U/ml (75.0%, 6/8). (2) Among the gynecological malignancies, the percent positivity was low in those with cervical cancer (20.0%, 5/25), endometrial cancer (33.3%, 1/3), and cancer of the fallopian tube (33.3%, 1/3). (3) The antigen was negative in 20 with myoma uteri, 20 normal pregnant women, and 9 nonpregnant healthy women during the follicular, luteal, or menstrual phase. It was negative in 8 of 9 patients with benign ovarian cyst. False negative results were rare. (4) The SLX level was higher in the ascites than in the serum in patients with ovarian cancer and in those with benign ovarian tumors. (5) The serum SLX in patients with ovarian cancer, which was positive before tumor resection, became negative 2 weeks postoperatively. These results suggest that SLX is a tumor marker with a high specificity to adenocarcinoma of the reproductive organs.     

CA 125 serum levels correlated with second-look operations among ovarian cancer patients

CA 125, which is an antigenic determinant expressed by many epithelial ovarian cancers, is measured in serum using a solid phase immunoradiometric assay. Sera from 55 patients who were in clinical remission and underwent a second-look operation to assess disease status after chemotherapy were studied prospectively. All patients had the CA 125 assay performed within one week before their second-look operation. Twenty-four patients (44%) had no histologic or cytologic evidence of disease, seven patients (13%) had microscopic disease, 13 patients (24%) had disease measuring 1 mm to 1.5 cm, and ten patients (18%) had disease greater than or equal to 1.5 cm in maximum tumor dimension. None of the 24 patients with a negative second-look operation had a positive CA 125 antigen level (greater than or equal to 35 U/mL), compared with six of 20 patients (30%) with less than 1.5 cm disease, and six of ten (60%) with greater than or equal to 1.5 cm disease (P less than .0001). All 12 patients with an elevated CA 125 antigen level (greater than or equal to 35 U/mL) had disease discovered at their second-look operation. Thus, in this setting the predictive value of a positive CA 125 titer (greater than or equal to 35 U/mL) was 100%. The predictive value of a negative CA 125 antigen level (less than 35 U/mL) was 56%, ie, the test did not exclude the presence of disease in 44% of patients with a positive second look. The maximum tumor size associated with at least one prior negative antigen level was 1.9 cm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictive value of CA 125 antigen levels in second-look procedures for ovarian cancer

Serum CA 125 levels were evaluated in 44 patients undergoing 56 second-look or subsequent laparoscopies (43) and laparotomies (13) for ovarian cancer. In each patient studied, a previous CA 125 level had been ⩾ 35 U/ml. Clinical or radiologic evidence of tumor was absent in all patients at the time of surgical evaluation. CA 125 levels were <35 U/ml in 36 cases (64%); 14 patients were free of tumor, while 22 were found to have tumor at surgery. CA 125 levels were ⩾35 U/ml in 20 cases; 18 had tumor at surgery, one has had recurrence of tumor, and the other remains clinically free of tumor at 3 months. A CA 125 level <35 U/ml was not predictive of the presence of intraperitoneal tumor; however, when tumor was present in this group of patients, the largest tumor mass did not exceed 1 cm. In contrast, a CA 125 level ⩾35 U/ml was a strong predictor of the presence of intraperitoneal tumor or future recurrence. These data suggest that second-look procedures may not be required in the select group of patients with CA 125 levels ⩾35 U/ml.     

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。?     

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.     

Immunohistological analysis of stress-induced phosphoprotein 1 in ovarian cancer patients with low serum cancer antigen 125 levels

ObjectiveStress-induced phosphoprotein 1 (STIP1) was recently identified as a potential tumor marker for human ovarian cancer. This study further evaluates the usefulness of STIP1 in ovarian tumor patients with normal CA125 serum levels.Materials and MethodsSTIP1 and CA125 were immunohistochemically analyzed in 84 primary ovarian cancer and 30 benign ovarian tumors in patients with serum CA125 levels < 35 U/mL before surgery. Histoscores (0–300) were calculated as staining intensities (0–3) multiplied by percentage of tumor tissue (0–100%).ResultsThe cell types of the 84 cancers included 11 serous, 10 clear-cell, 51 mucinous, and 12 endometrioid carcinomas. There were 55 patients with invasive cancer and 29 with borderline ovarian tumors. The histoscores of STIP1, but not of CA125, in invasive cancer (mean ± SD, 186.3 ± 82.5) were significantly (p < 0.0001) higher than those seen in borderline ovarian tumors (86.2 ± 85.5). When the STIP1 histoscore was set at 183.8, invasive cancers (n = 55) were identified from benign tumors (n = 30) with a sensitivity of 56.4%, a specificity of 93.3%, a positive predictive value of 93.9%, and a negative predictive value of 53.8%. Results of receiver operating characteristics analysis showed that the area under curve of the STIP1 histoscore was 0.755, which was superior to that of CA125 (0.599).ConclusionSTIP1 histoscores may be useful in detecting invasive human ovarian cancer in patients with low serum CA125 levels.     

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)     

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.